@article {pmid39672950,
year = {2024},
author = {Tournebize, R and Chikhi, L},
title = {Ignoring population structure in hominin evolutionary models can lead to the inference of spurious admixture events.},
journal = {Nature ecology & evolution},
volume = {},
number = {},
pages = {},
pmid = {39672950},
issn = {2397-334X},
support = {ANR-10-LABX-25-01//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-10-LABX-25-01//Agence Nationale de la Recherche (French National Research Agency)/ ; },
abstract = {Genomic and ancient DNA data have revolutionized palaeoanthropology and our vision of human evolution, with indisputable landmarks like the sequencing of Neanderthal and Denisovan genomes. Yet, using genetic data to identify, date and quantify evolutionary events-such as ancient bottlenecks or admixture-is not straightforward, as inferences may depend on model assumptions. In the last two decades, the idea that Neanderthals and members of the Homo sapiens lineage interbred has gained momentum. From the status of unlikely theory, it has reached consensus among human evolutionary biologists. This theory is mainly supported by statistical approaches that depend on demographic models minimizing or ignoring population structure, despite its widespread occurrence and the fact that, when ignored, population structure can lead to the inference of spurious demographic events. We simulated genomic data under a structured and admixture-free model of human evolution, and found that all the tested admixture approaches identified long Neanderthal fragments in our simulated genomes and an admixture event that never took place. We also observed that several published admixture models failed to predict important empirical diversity or admixture statistics, and that we could identify several scenarios from our structured model that better predicted these statistics jointly. Using a simulated time series of ancient DNA, the structured scenarios could also predict the trajectory of the empirical D statistics. Our results suggest that models accounting for population structure are fundamental to improve our understanding of human evolution, and that admixture between Neanderthals and H. sapiens needs to be re-evaluated in the light of structured models. Beyond the Neanderthal case, we argue that ancient hybridization events, which are increasingly documented in many species, including with other hominins, may also benefit from such re-evaluation.},
}

@article {pmid39672157,
year = {2024},
author = {Li, Q and Faux, P and Wentworth Winchester, E and Yang, G and Chen, Y and Ramírez, LM and Fuentes-Guajardo, M and Poloni, L and Steimetz, E and Gonzalez-José, R and Acuña, V and Bortolini, MC and Poletti, G and Gallo, C and Rothhammer, F and Rojas, W and Zheng, Y and Cox, JC and Patel, V and Hoffman, MP and Ding, L and Peng, C and Cotney, J and Navarro, N and Cox, TC and Delgado, M and Adhikari, K and Ruiz-Linares, A},
title = {PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans.},
journal = {Current biology : CB},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cub.2024.11.027},
pmid = {39672157},
issn = {1879-0445},
abstract = {Dental morphology varies greatly throughout evolution, including in the human lineage, but little is known about the biology of this variation. Here, we use multiomics analyses to examine the genetics of variation in tooth crown dimensions. In a human cohort with mixed continental ancestry, we detected genome-wide significant associations at 18 genome regions. One region includes EDAR, a gene known to impact dental features in East Asians. Furthermore, we find that EDAR variants increase the mesiodistal diameter of all teeth, following an anterior-posterior gradient of decreasing strength. Among the 17 novel-associated regions, we replicate 7/13 in an independent human cohort and find that 4/12 orthologous regions affect molar size in mice. Two association signals point to compelling candidate genes. One is ∼61 kb from PITX2, a major determinant of tooth development. Another overlaps HS3ST3A1, a paralogous neighbor of HS3ST3B1, a tooth enamel knot factor. We document the expression of Pitx2 and Hs3st3a1 in enamel knot and dental epithelial cells of developing mouse incisors. Furthermore, associated SNPs in PITX2 and HS3ST3A1 overlap enhancers active in these cells, suggesting a role for these SNPs in gene regulation during dental development. In addition, we document that Pitx2 and Hs3st3a1/Hs3st3b1 knockout mice show alterations in dental morphology. Finally, we find that associated SNPs in HS3ST3A1 are in a DNA tract introgressed from Neanderthals, consistent with an involvement of HS3ST3A1 in tooth size variation during human evolution.},
}

@article {pmid39667410,
year = {2024},
author = {Sümer, AP and Rougier, H and Villalba-Mouco, V and Huang, Y and Iasi, LNM and Essel, E and Mesa, AB and Furtwaengler, A and Peyrégne, S and de Filippo, C and Rohrlach, AB and Pierini, F and Mafessoni, F and Fewlass, H and Zavala, EI and Mylopotamitaki, D and Bianco, RA and Schmidt, A and Zorn, J and Nickel, B and Patova, A and Posth, C and Smith, GM and Ruebens, K and Sinet-Mathiot, V and Stoessel, A and Dietl, H and Orschiedt, J and Kelso, J and Zeberg, H and Bos, KI and Welker, F and Weiss, M and McPherron, S and Schüler, T and Hublin, JJ and Velemínský, P and Brůžek, J and Peter, BM and Meyer, M and Meller, H and Ringbauer, H and Hajdinjak, M and Prüfer, K and Krause, J},
title = {Earliest modern human genomes constrain timing of Neanderthal admixture.},
journal = {Nature},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41586-024-08420-x},
pmid = {39667410},
issn = {1476-4687},
abstract = {Modern humans arrived in Europe more than 45,000 years ago, overlapping at least 5,000 years with Neanderthals[1-4]. Limited genomic data from these early modern humans have shown that at least two genetically distinct groups inhabited Europe, represented by Zlatý kůň, Czechia[3] and Bacho Kiro, Bulgaria[2]. Here we deepen our understanding of early modern humans by analyzing one high-coverage genome and five low-coverage genomes from ~45,000 year-old remains from Ilsenhöhle in Ranis, Germany[4], and a further high-coverage genome from Zlatý kůň. We show that distant familial relationships link the Ranis and Zlatý kůň individuals and that they were part of the same small, isolated population that represents the deepest known split from the Out-of-Africa lineage. Ranis genomes harbor Neanderthal segments that originate from a single admixture event shared with all non-Africans that we date to ~45,000-49,000 years ago. This implies that ancestors of all non-Africans sequenced to-date resided in a common population at this time, and further suggests that modern human remains older than 50,000 years from outside Africa represent different non-African populations.},
}

@article {pmid39667186,
year = {2024},
author = {López-Rey, JM and García-Martínez, D and Bastir, M},
title = {Shanidar 3 'rings the bell': Virtual ribcage reconstruction and its implications for understanding the Neanderthal bauplan.},
journal = {Journal of human evolution},
volume = {199},
number = {},
pages = {103629},
doi = {10.1016/j.jhevol.2024.103629},
pmid = {39667186},
issn = {1095-8606},
abstract = {The study of the ribcage is fundamental to understanding hominin evolution. However, ribs and vertebrae are scarce in the fossil record. Although Neanderthals are one of the most represented and, therefore, one of the most studied fossil Homo species, it is controversial whether there is a standardized Neanderthal ribcage morphotype that could differ from modern humans. Hence, we used three-dimensional geometric morphometrics to reconstruct and compare the Neanderthal ribcage of Shanidar 3 with another Neanderthal specimen, Kebara 2, and with 58 Homo sapiens individuals of worldwide distribution. Shape differences among the Neanderthal and H. sapiens ribcages were analyzed by a hierarchical cluster using the Euclidean distances among the permuted Procrustes distances between groups. Size differences between the Neanderthal and H. sapiens ribcages were examined using a permutation test on centroid size. To examine the potential for allometry, we performed a linear regression of Procrustes coordinates on centroid size of the sample, followed by a principal component analysis in form space. Our results show that Shanidar 3 has the 'bell-shaped' thorax typically described for Neanderthals. In fact, the shapes of both Shanidar 3 and Kebara 2 ribcages cluster apart from that of H. sapiens, being closer to cold-adapted individuals. The study of the centroid size supports similarities between Neanderthals and cold-adapted H. sapiens since significant size differences were found only between Neanderthals and temperate/tropical recent humans. The linear regression and principal component analysis showed an allometric relationship between ribcage size and shape, suggesting Neanderthals had larger and stockier ribcages than most H. sapiens, although they fall within the H. sapiens range of variation. Finally, ribcage similarities found between Shanidar 3 and Kebara 2, both inhabiting warm Levantine locations during the Upper Pleistocene, could challenge the conventional idea of a cold-adapted bauplan in Neanderthals.},
}

@article {pmid39666853,
year = {2024},
author = {Iasi, LNM and Chintalapati, M and Skov, L and Mesa, AB and Hajdinjak, M and Peter, BM and Moorjani, P},
title = {Neanderthal ancestry through time: Insights from genomes of ancient and present-day humans.},
journal = {Science (New York, N.Y.)},
volume = {386},
number = {6727},
pages = {eadq3010},
doi = {10.1126/science.adq3010},
pmid = {39666853},
issn = {1095-9203},
mesh = {*Neanderthals/genetics ; Animals ; *Gene Flow ; Humans ; *Genome, Human ; *Selection, Genetic ; DNA, Ancient/analysis ; },
abstract = {Gene flow from Neanderthals has shaped genetic and phenotypic variation in modern humans. We generated a catalog of Neanderthal ancestry segments in more than 300 genomes spanning the past 50,000 years. We examined how Neanderthal ancestry is shared among individuals over time. Our analysis revealed that the vast majority of Neanderthal gene flow is attributable to a single, shared extended period of gene flow that occurred between 50,500 to 43,500 years ago, as evidenced by ancestry correlation, colocalization of Neanderthal segments across individuals, and divergence from the sequenced Neanderthals. Most natural selection-positive and negative-on Neanderthal variants occurred rapidly after the gene flow. Our findings provide new insights into how contact with Neanderthals shaped modern human origins and adaptation.},
}

*Neanderthals/genetics
Animals
*Gene Flow
Humans
*Genome, Human
*Selection, Genetic
DNA, Ancient/analysis

@article {pmid39577372,
year = {2024},
author = {Tagore, D and Akey, JM},
title = {Archaic hominin admixture and its consequences for modern humans.},
journal = {Current opinion in genetics & development},
volume = {90},
number = {},
pages = {102280},
doi = {10.1016/j.gde.2024.102280},
pmid = {39577372},
issn = {1879-0380},
abstract = {As anatomically modern humans dispersed out of Africa, they encountered and mated with now extinct hominins, including Neanderthals and Denisovans. It is now well established that all non-African individuals derive approximately 2% of their genome from Neanderthal ancestors and individuals of Melanesian and Australian aboriginal ancestry inherited an additional 2%-5% of their genomes from Denisovan ancestors. Attention has started to shift from documenting amounts of archaic admixture and identifying introgressed segments to understanding their molecular, phenotypic, and evolutionary consequences and refining models of human history. Here, we review recent insights into admixture between modern and archaic humans, emphasizing methodological innovations and the functional and phenotypic effects Neanderthal and Denisovan sequences have in contemporary individuals.},
}

@article {pmid39565777,
year = {2024},
author = {Richards, MP and Mannino, MA and Jaouen, K and Dozio, A and Hublin, JJ and Peresani, M},
title = {Correction: Strontium isotope evidence for Neanderthal and modern human mobility at the upper and middle palaeolithic site of Fumane Cave (Italy).},
journal = {PloS one},
volume = {19},
number = {11},
pages = {e0314425},
pmid = {39565777},
issn = {1932-6203},
abstract = {[This corrects the article DOI: 10.1371/journal.pone.0254848.].},
}

@article {pmid39523570,
year = {2024},
author = {Lozano, M and Soler, J and López-Onaindia, D and Solés, A and Julià, R and Ceperuelo, D and Lorenzo, C and Soler, N},
title = {Middle Pleistocene teeth from Arbreda Cave (Serinyà, northeastern Iberian Peninsula).},
journal = {American journal of biological anthropology},
volume = {185},
number = {4},
pages = {e25037},
doi = {10.1002/ajpa.25037},
pmid = {39523570},
issn = {2692-7691},
support = {PACEA-UMR5199//EVODIBIO and EURAPAL/ ; PID2021-122355NB-C32//the Spanish Ministry of Science and Innovation through the "María de Maeztu" excellence accreditation (CEX2019-000945- M), from the FEDER/Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación/ ; N°895713Neander-TALe//Marie Skłodowska-Curie Actions/ ; CLT009/18/00092//Departament de Cultura de la Generalitat de Catalunya/ ; IdEx "Investments for the Future" program / GPR Hu//University of Bordeaux/ ; POS_2019_1_0024//Basque Government postdoctoral Fellowship/ ; 2017SGR-1688//AGAUR/ ; 22021SGR01239//AGAUR/ ; },
mesh = {Spain ; Animals ; *Neanderthals/anatomy & histology ; *Fossils ; Humans ; *Caves ; *Tooth/anatomy & histology/chemistry ; Adult ; Infant ; Paleodontology ; X-Ray Microtomography ; Molar/anatomy & histology/chemistry ; },
abstract = {OBJECTIVES: We report the discovery and description of three human teeth from the Middle Paleolithic archaeological levels of Arbreda Cave (Serinyà, Catalonia, NE Iberian Peninsula).

MATERIALS AND METHODS: The teeth, two molars (one right dm2 and one right M2) from Level N (older than 120 kyr) and one P[3] from Level J (dated between 71 and 44 kyr), were morphologically described based on microCT images and compared with Neanderthal and Homo sapiens specimens.

RESULTS: The teeth belong to a minimum of three individuals: one adult and one infant from Level N and one juvenile from Level J. The premolar from Mousterian Level J, the best preserved of the three teeth, exhibits characteristics to those from our comparative sample of Homo neanderthalensis, such as the crown measurements, EDJ traits, enamel thickness and volume of the pulp cavity.

DISCUSSION: In contrast to the clear Neanderthal characteristics observed in the P[3] from Level J, the high degree of dental wear and poor state of preservation precludes definitive taxonomic designations of the two teeth from Level N. However, the crown dimensions and some tissue proportions are consistent with a probable assignation to Homo neanderthalensis. The teeth from Level N come from a context of long and recurrent occupations of the cave, whereas the archaeological context of the tooth from Level J is indicative of short and seasonal occupations of the cave, which may indicate a change in the lifestyle strategies of the last Neanderthals of the Iberian Peninsula.},
}

Spain
Animals
*Neanderthals/anatomy & histology
*Fossils
Humans
*Caves
*Tooth/anatomy & histology/chemistry
Adult
Infant
Paleodontology
X-Ray Microtomography
Molar/anatomy & histology/chemistry

@article {pmid39502191,
year = {2024},
author = {Pilliol, V and Mahmoud Abdelwadoud, B and Aïcha, H and Lucille, T and Gérard, A and Hervé, T and Michel, D and Ghiles, G and Elodie, T},
title = {Methanobrevibacter oralis: a comprehensive review.},
journal = {Journal of oral microbiology},
volume = {16},
number = {1},
pages = {2415734},
pmid = {39502191},
issn = {2000-2297},
abstract = {Methanobrevibacter oralis (M. oralis) has predominated human oral microbiota methanogenic archaea as far back as the Palaeolithic era in Neanderthal populations and gained dominance from the 18[th] century onwards. M. oralis was initially isolated from dental plaque samples collected from two apparently healthy individuals allowing its first characterization. The culture of M. oralis is fastidious and has been the subject of several studies to improve its laboratory growth. Various PCR methods are used to identify M. oralis, targeting either the 16S rRNA gene or the mcrA gene. However, only one RTQ-PCR system, based on a chaperonin gene, offers specificity, and allows for microbial load quantification. Next-generation sequencing contributed five draft genomes, each approximately 2.08 Mb (±0.052 Mb) with a 27.82 (±0.104) average GC%, and two ancient metagenomic assembled genomes. M. oralis was then detected in various oral cavity sites in healthy individuals and those diagnosed with oral pathologies, notably periodontal diseases, and endodontic infections. Transmission pathways, possibly involving maternal milk and breastfeeding, remain to be clarified. M. oralis was further detected in brain abscesses and respiratory tract samples, bringing its clinical significance into question. This review summarizes the current knowledge about M. oralis, emphasizing its prevalence, associations with dysbiosis and pathologies in oral and extra-oral situations, and symbiotic relationships, with the aim of paving the way for further investigations.},
}

@article {pmid39501127,
year = {2024},
author = {Ongaro, L and Huerta-Sanchez, E},
title = {A history of multiple Denisovan introgression events in modern humans.},
journal = {Nature genetics},
volume = {56},
number = {12},
pages = {2612-2622},
pmid = {39501127},
issn = {1546-1718},
mesh = {Humans ; Animals ; *Genome, Human ; *Hominidae/genetics ; *Fossils ; Genetic Introgression ; Neanderthals/genetics ; Phylogeny ; Selection, Genetic ; Evolution, Molecular ; Biological Evolution ; Genetics, Population ; },
abstract = {The identification of a new hominin group in the Altai mountains called Denisovans was one of the most exciting discoveries in human evolution in the last decade. Unlike Neanderthal remains, the Denisovan fossil record consists of only a finger bone, jawbone, teeth and skull fragments. Leveraging the surviving Denisovan segments in modern human genomes has uncovered evidence of at least three introgression events from distinct Denisovan populations into modern humans in the past. Each of them presents different levels of relatedness to the sequenced Altai Denisovan, indicating a complex relationship between these sister lineages. Here we review the evidence suggesting that several Denisovan populations, who likely had an extensive geographical range, were adapted to distinct environments and introgressed into modern humans multiple times. We further discuss how archaic variants have been affected by demographic history, negative and positive selection and close by proposing possible new lines of future research.},
}

Humans
Animals
*Genome, Human
*Hominidae/genetics
*Fossils
Genetic Introgression
Neanderthals/genetics
Phylogeny
Selection, Genetic
Evolution, Molecular
Biological Evolution
Genetics, Population

@article {pmid39429655,
year = {2024},
author = {Farhud, DD and Azari, M and Rahbar, M},
title = {Tuberculosis in Human Bones from 4000 Years Ago, Iran.},
journal = {Iranian journal of public health},
volume = {53},
number = {9},
pages = {2103-2112},
pmid = {39429655},
issn = {2251-6093},
abstract = {BACKGROUND: Tuberculosis is caused by a bacterium called Mycobacterium tuberculosis, which is a contagious and infectious disease; in the first stage, it destroys the lungs and in the next stage other body organs, such as the spine and long bones. This disease is transmitted through an infected person and due to the weakness of the immune system, the infection intensifies. Tuberculosis has two stages: low activity and high activity. In this article, we have discussed the signs of tuberculosis destruction with high intensity on the bones of prehistory human remains.

METHODS: The examples of our research are related to human remains from the ancient cemetery of 4000 years ago from Sagezabad region of Qazvin Province of Iran. That period of history coincides with the Iron Age 2 and 3 in the region. People inside the Sagezabad cemetery were very near to early urban (the late rural) society.

RESULTS: By matching the form of bone destruction with international atlases for tuberculosis, we have reached a satisfactory result in this article. Due to the strong penetration of the infection into the bones, destruction in the remains was high, so it has simplified the diagnosis for us.

CONCLUSION: We found tuberculosis among the bones. This common ancient disease existed even among Neanderthals.},
}

@article {pmid39357284,
year = {2024},
author = {Fuchs, J and García-Tabernero, A and Rosas, A and Camus, H and Metz, L and Slimak, L and Zanolli, C},
title = {The dentition of a new adult Neanderthal individual from Grotte Mandrin, France.},
journal = {Journal of human evolution},
volume = {196},
number = {},
pages = {103599},
doi = {10.1016/j.jhevol.2024.103599},
pmid = {39357284},
issn = {1095-8606},
mesh = {*Neanderthals/anatomy & histology/genetics ; Animals ; France ; *Fossils/anatomy & histology ; Male ; Tooth/anatomy & histology ; Dentition ; X-Ray Microtomography ; },
abstract = {Grotte Mandrin is located in the middle Rhône River Valley, in Mediterranean France, and has yielded 11 Pleistocene archeological and paleoanthropological layers (ranging from the oldest layer J to the youngest layer B) dating from Marine Isotope Stage (MIS) 5 to MIS 3. We report here the nearly complete dentition of an adult Neanderthal individual, nicknamed 'Thorin,' associated to the last phase of the Post-Neronian II, in layer B2 (∼44.50-42.25 ka). A previous paleogenetic analysis revealed that Thorin is a male individual and that he shows a deep genetic divergence with other penecontemporaneous Neanderthals from western Europe that possibly occurred ∼105 ka. The 31 teeth of Thorin (including two distomolars) are described and analyzed using microcomputed tomography imaging and are compared with other Neanderthals and modern humans. Based on direct observation and measurements on the fossil remains, and using microtomographic imaging, tooth wear, nonmetric characters, crown dimensions, and dental tissue proportions were investigated, and the shape of the enamel-dentine junction of the M[2], M2, and M3 was analyzed by geometric morphometrics. Our results indicate that Thorin's teeth show dental characteristics typical of MIS 5-3 Neanderthals. It is also the first time that the presence of two distomolars is reported in a Neanderthal individual, a trait that is rare among modern human populations. Combined with the genetic peculiarities of this individual, the results of the present study imply either a process of morphological convergence among the latest Neanderthal groups or an underestimation of the genetic variability of recent Neanderthal groups.},
}

*Neanderthals/anatomy & histology/genetics
Animals
France
*Fossils/anatomy & histology
Male
Tooth/anatomy & histology
Dentition
X-Ray Microtomography

@article {pmid39333171,
year = {2024},
author = {Sánchez-Yustos, P and Marín-Arroyo, AB and Arnold, LJ and Luque, L and Kehl, M and López-Sáez, JA and Carrancho Alonso, Á and Demuro, M and Sanz-Royo, A and Buckley, M and Maíllo-Fernández, JM and Cuartero-Monteagudo, F and Llamazares-González, J and Ruiz-Alonso, M and Luelmo-Lautenschlaeger, R and García-Soto, E and Alcaraz-Castaño, M},
title = {Initial Upper Palaeolithic lithic industry at Cueva Millán in the hinterlands of Iberia.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {21705},
pmid = {39333171},
issn = {2045-2322},
support = {818299//the European Research Council/ ; 805478/ERC_/European Research Council/International ; },
mesh = {*Archaeology ; Animals ; Humans ; *Neanderthals ; Spain ; Fossils/history ; Industry/history ; History, Ancient ; },
abstract = {The extended period of coexistence between Neanderthals and Homo sapiens in Europe coincided with the emergence of regionally distinctive lithic industries, signalling the onset of the Upper Palaeolithic. The Iberian Peninsula was on the periphery of pioneering Upper Palaeolithic developments, with archaeological remains primarily found in northern territories. We report the discovery of an initial Upper Palaeolithic lithic industry at Cueva Millán in the hinterlands of Iberia. This industry, termed here Arlanzian, not only represents the earliest and southernmost evidence of such industries in Iberia but also lacks a direct counterpart. However, it exhibits chronological and technological parallels with the lithic industries associated with the earliest expansion of Homo sapiens throughout Eurasia. We interpret this as potential evidence of its intrusive nature, but not necessarily associated with a migration event, as more complex scenarios derived from inter-population connectivity must be also considered. The biological identity of the Arlanzian makers remains unknown, but they coexisted with declining Neanderthal groups from neighbouring territories.},
}

*Archaeology
Animals
Humans
*Neanderthals
Spain
Fossils/history
Industry/history
History, Ancient

@article {pmid39288002,
year = {2024},
author = {Relethford, JH},
title = {Craniometric variation and the ancestry of modern humans.},
journal = {American journal of biological anthropology},
volume = {185},
number = {4},
pages = {e25028},
doi = {10.1002/ajpa.25028},
pmid = {39288002},
issn = {2692-7691},
mesh = {Animals ; Female ; Humans ; Male ; Africa South of the Sahara/ethnology ; Anthropology, Physical ; *Cephalometry ; *Neanderthals/genetics ; *Skull/anatomy & histology ; White People ; Sub-Saharan African People ; Asian People ; },
abstract = {OBJECTIVES: Ancient and contemporary DNA provide information about geographic variation in the ancestry of present-day humans. All living populations have ancestry from early Homo sapiens originating in sub-Saharan Africa. Populations of Eurasian descent also have a small amount of Neandertal ancestry. This study examines whether craniometric distances between recent modern human samples reflect this geographic variation in ancestry. Among recent modern humans, Eurasians are expected to be more similar to Neandertals, whereas both sub-Saharan Africans and Eurasians are expected to be equidistant from early H. sapiens.

MATERIALS AND METHODS: Data on 33 craniometric traits from 2524 recent modern humans were compared with data from the literature for Neandertals and early H. sapiens. Mahalanobis distances were computed for each modern specimen to both the Neandertal and early H. sapiens means. These distances were examined for differences between recent humans from sub-Saharan Africa (N = 373) and those of Eurasian descent (N = 2151).

RESULTS: Eurasians as a group are significantly closer than sub-Saharan Africans to Neandertals. There is no significant difference between the distances of sub-Saharan Africans and Eurasians to early H. sapiens.

DISCUSSION: The differences between sub-Saharan Africans and Eurasians for both Neandertals and early H. sapiens are as expected. Although there has been geographic differentiation among recent modern humans, including differences in Neandertal admixture, these differences have not affected overall similarity of recent modern sub-Saharan Africans and Eurasians to the earliest samples of H. sapiens.},
}

Animals
Female
Humans
Male
Africa South of the Sahara/ethnology
Anthropology, Physical
*Cephalometry
*Neanderthals/genetics
*Skull/anatomy & histology
White People
Sub-Saharan African People
Asian People

@article {pmid39271648,
year = {2024},
author = {Higham, T and Frouin, M and Douka, K and Ronchitelli, A and Boscato, P and Benazzi, S and Crezzini, J and Spagnolo, V and McCarty, M and Marciani, G and Falcucci, A and Rossini, M and Arrighi, S and Dominici, C and Devièse, T and Schwenninger, JL and Martini, I and Moroni, A and Boschin, F},
title = {Chronometric data and stratigraphic evidence support discontinuity between Neanderthals and early Homo sapiens in the Italian Peninsula.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {8016},
pmid = {39271648},
issn = {2041-1723},
support = {324139//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science-European Research Council)/ ; },
mesh = {*Neanderthals ; Italy ; Animals ; Humans ; *Bayes Theorem ; *Fossils ; Radiometric Dating/methods ; Archaeology/methods ; History, Ancient ; },
abstract = {The process by which Palaeolithic Europe was transformed from a Neanderthal-dominated region to one occupied exclusively by Homo sapiens has proven challenging to diagnose. A blurred chronology has made it difficult to determine when Neanderthals disappeared and whether modern humans overlapped with them. Italy is a crucial region because here we can identify not only Late Mousterian industries, assumed to be associated with Neanderthals, but also early Upper Palaeolithic industries linked with the appearance of early H. sapiens, such as the Uluzzian and the Aurignacian. Here, we present a chronometric dataset of 105 new determinations (74 radiocarbon and 31 luminescence ages) from four key southern Italian sites: Cavallo, Castelcivita, Cala, and Oscurusciuto. We built Bayesian-based chronometric models incorporating these results alongside the relative stratigraphic sequences at each site. The results suggest; 1) that the disappearance of Neanderthals probably pre-dated the appearance of early modern humans in the region and; 2) that there was a partial overlap in the chronology of the Uluzzian and Protoaurignacian, suggesting that these industries may have been produced by different human groups in Europe.},
}

*Neanderthals
Italy
Animals
Humans
*Bayes Theorem
*Fossils
Radiometric Dating/methods
Archaeology/methods
History, Ancient

@article {pmid39265525,
year = {2024},
author = {Slimak, L and Vimala, T and Seguin-Orlando, A and Metz, L and Zanolli, C and Joannes-Boyau, R and Frouin, M and Arnold, LJ and Demuro, M and Devièse, T and Comeskey, D and Buckley, M and Camus, H and Muth, X and Lewis, JE and Bocherens, H and Yvorra, P and Tenailleau, C and Duployer, B and Coqueugniot, H and Dutour, O and Higham, T and Sikora, M},
title = {Long genetic and social isolation in Neanderthals before their extinction.},
journal = {Cell genomics},
volume = {4},
number = {9},
pages = {100593},
pmid = {39265525},
issn = {2666-979X},
mesh = {*Neanderthals/genetics ; Animals ; *Fossils ; Social Isolation ; Humans ; Genome ; Extinction, Biological ; France ; },
abstract = {Neanderthal genomes have been recovered from sites across Eurasia, painting an increasingly complex picture of their populations' structure that mostly indicates that late European Neanderthals belonged to a single metapopulation with no significant evidence of population structure. Here, we report the discovery of a late Neanderthal individual, nicknamed "Thorin," from Grotte Mandrin in Mediterranean France, and his genome. These dentognathic fossils, including a rare example of distomolars, are associated with a rich archeological record of Neanderthal final technological traditions in this region ∼50-42 thousand years ago. Thorin's genome reveals a relatively early divergence of ∼105 ka with other late Neanderthals. Thorin belonged to a population with a small group size that showed no genetic introgression with other known late European Neanderthals, revealing some 50 ka of genetic isolation of his lineage despite them living in neighboring regions. These results have important implications for resolving competing hypotheses about causes of the disappearance of the Neanderthals.},
}

*Neanderthals/genetics
Animals
*Fossils
Social Isolation
Humans
Genome
Extinction, Biological
France

@article {pmid39261722,
year = {2024},
author = {Sun, W and Yang, T and Sun, F and Liu, P and Gao, J and Lan, X and Xu, W and Pang, Y and Li, T and Li, C and Liang, Q and Chen, H and Liu, X and Tan, W and Zhu, H and Wang, F and Cheng, F and Zhai, W and Kim, HN and Zhang, J and Zhang, L and Lu, L and Xi, Q and Deng, G and Huang, Y and Jin, X and Chen, X and Liu, W},
title = {An IGHG1 variant exhibits polarized prevalence and confers enhanced IgG1 antibody responses against life-threatening organisms.},
journal = {Nature immunology},
volume = {25},
number = {10},
pages = {1809-1819},
pmid = {39261722},
issn = {1529-2916},
support = {2021YFC2300503//Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)/ ; 2021YFC2302403//Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)/ ; 32141004//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81825010//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81930061//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Humans ; Animals ; *Immunoglobulin G/immunology ; *COVID-19/immunology/genetics ; *SARS-CoV-2/immunology ; Mice ; *Immunoglobulin Heavy Chains/genetics/immunology ; Linkage Disequilibrium ; Antibody Formation/genetics/immunology ; Haplotypes ; Memory B Cells/immunology ; Female ; Genetic Variation ; Male ; },
abstract = {Evolutionary pressures sculpt population genetics, whereas immune adaptation fortifies humans against life-threatening organisms. How the evolution of selective genetic variation in adaptive immune receptors orchestrates the adaptation of human populations to contextual perturbations remains elusive. Here, we show that the G396R coding variant within the human immunoglobulin G1 (IgG1) heavy chain presents a concentrated prevalence in Southeast Asian populations. We uncovered a 190-kb genomic linkage disequilibrium block peaked in close proximity to this variant, suggestive of potential Darwinian selection. This variant confers heightened immune resilience against various pathogens and viper toxins in mice. Mechanistic studies involving severe acute respiratory syndrome coronavirus 2 infection and vaccinated individuals reveal that this variant enhances pathogen-specific IgG1[+] memory B cell activation and antibody production. This G396R variant may have arisen on a Neanderthal haplotype background. These findings underscore the importance of an IGHG1 variant in reinforcing IgG1 antibody responses against life-threatening organisms, unraveling the intricate interplay between human evolution and immune adaptation.},
}

Humans
Animals
*Immunoglobulin G/immunology
*COVID-19/immunology/genetics
*SARS-CoV-2/immunology
Mice
*Immunoglobulin Heavy Chains/genetics/immunology
Linkage Disequilibrium
Antibody Formation/genetics/immunology
Haplotypes
Memory B Cells/immunology
Female
Genetic Variation
Male

@article {pmid39241178,
year = {2024},
author = {Caporale, AL and Cinalli, AR and Rubinstein, M and Franchini, LF},
title = {The Human Accelerated Region HAR202 Controls NPAS3 Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences.},
journal = {Molecular biology and evolution},
volume = {41},
number = {10},
pages = {},
pmid = {39241178},
issn = {1537-1719},
support = {//Agencia Nacional de Promoción Científica y Tecnológica/ ; },
mesh = {Animals ; Humans ; *Prosencephalon/metabolism ; *Nerve Tissue Proteins/genetics/metabolism ; *Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; Mice ; *Zebrafish/genetics ; *Enhancer Elements, Genetic ; Evolution, Molecular ; Mice, Transgenic ; Gene Expression Regulation, Developmental ; },
abstract = {It has been proposed that the phenotypic differences in cognitive abilities between humans and our closest living relatives, chimpanzees, are largely due to changes in the regulation of neurodevelopmental genes. We have previously found that the neurodevelopmental transcription factor gene NPAS3 accumulates the largest number of human accelerated regions (HARs), suggesting it may play some role in the phenotypic evolution of the human nervous system. In this work, we performed a comparative functional analysis of NPAS3-HAR202 using enhancer reporter assays in transgenic zebrafish and mice. We found that the Homo sapiens HAR202 ortholog failed to drive reporter expression to the zebrafish nervous system, in high contrast to the strong expression displayed by the rest of the vertebrate ortholog sequences tested. Remarkably, the HAR202 ortholog from archaic humans (Neanderthals/Denisovans) also displayed a pan-vertebrate expression pattern, despite the fact that archaic and modern humans have only one nucleotide substitution. Moreover, similar results were found when comparing enhancer activity in transgenic mice, where we observed a loss of activity of the modern human version in the mouse developing brain. To investigate the functional importance of HAR202, we generated mice lacking HAR202 and found a remarkable decrease of Npas3 expression in the forebrain during development. Our results place HAR202 as one of the very few examples of a neurodevelopmental transcriptional enhancer displaying functional evolution in the brain as a result of a fast molecular evolutionary process that specifically occurred in the human lineage.},
}

Animals
Humans
*Prosencephalon/metabolism
*Nerve Tissue Proteins/genetics/metabolism
*Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism
Mice
*Zebrafish/genetics
*Enhancer Elements, Genetic
Evolution, Molecular
Mice, Transgenic
Gene Expression Regulation, Developmental

@article {pmid39227658,
year = {2024},
author = {Richard, M and Del Val, M and Fewlass, H and Sinet-Mathiot, V and Lanos, P and Pons-Branchu, E and Puaud, S and Hublin, JJ and Moncel, MH},
title = {Multi-method dating reveals 200 ka of Middle Palaeolithic occupation at Maras rock shelter, Rhône Valley, France.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {20474},
pmid = {39227658},
issn = {2045-2322},
mesh = {*Neanderthals ; *Archaeology ; Animals ; *Radiometric Dating/methods ; France ; Humans ; Fossils ; Tooth/anatomy & histology ; Geologic Sediments/analysis ; Bayes Theorem ; Bone and Bones/anatomy & histology ; Electron Spin Resonance Spectroscopy/methods ; Uranium/analysis ; History, Ancient ; },
abstract = {The emergence of the Middle Palaeolithic, and its variability over time and space are key questions in the field of prehistoric archaeology. Many sites have been documented in the south-eastern margins of the Massif central and the middle Rhône valley, a migration path that connects Northern Europe with the Mediterranean. Well-dated, long stratigraphic sequences are essential to understand Neanderthals dynamics and demise, and potential interactions with Homo sapiens in the area, such as the one displayed at the Maras rock shelter ("Abri du Maras"). The site is characterised by exceptional preservation of archaeological remains, including bones dated using radiocarbon ([14]C) and teeth using electron spin resonance combined with uranium series (ESR/U-series). Optically stimulated luminescence was used to date the sedimentary deposits. By combining the new ages with previous ones using Bayesian modelling, we are able to clarify the occupation time over a period spanning 200,000 years. Between ca. 250 and 40 ka, the site has been used as a long-term residence by Neanderthals, specifically during three interglacial periods: first during marine isotopic stage (MIS) 7, between 247 ± 34 and 223 ± 33 ka, and then recurrently during MIS 5 (between 127 ± 17 and 90 ± 9 ka) and MIS 3 (up to 39,280 cal BP).},
}

*Neanderthals
*Archaeology
Animals
*Radiometric Dating/methods
France
Humans
Fossils
Tooth/anatomy & histology
Geologic Sediments/analysis
Bayes Theorem
Bone and Bones/anatomy & histology
Electron Spin Resonance Spectroscopy/methods
Uranium/analysis
History, Ancient

@article {pmid39227643,
year = {2024},
author = {Guran, SH and Yousefi, M and Kafash, A and Ghasidian, E},
title = {Reconstructing contact and a potential interbreeding geographical zone between Neanderthals and anatomically modern humans.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {20475},
pmid = {39227643},
issn = {2045-2322},
support = {402379177//Deutsche Forschungsgemeinschaft/ ; },
mesh = {*Neanderthals ; Animals ; Humans ; *Fossils ; Archaeology ; Geography ; },
abstract = {While the interbreeding of Homo neanderthalensis (hereafter Neanderthal) and Anatomically modern human (AMH) has been proven, owing to the shortage of fossils and absence of appropriate DNA, the timing and geography of their interbreeding are not clearly known. In this study, we applied ecological niche modelling (maximum entropy approach) and GIS to reconstruct the palaeodistribution of Neanderthals and AMHs in Southwest Asia and Southeast Europe and identify their contact and potential interbreeding zone during marine isotope stage 5 (MIS 5), when the second wave of interbreeding occurred. We used climatic variables characterizing the environmental conditions of MIS 5 ca. 120 to 80 kyr (averaged value) along with the topography and coordinates of Neanderthal and modern human archaeological sites to characterize the palaeodistribution of each species. Overlapping the models revealed that the Zagros Mountains were a contact and potential interbreeding zone for the two human species. We believe that the Zagros Mountains acted as a corridor connecting the Palearctic/Afrotropical realms, facilitating northwards dispersal of AMHs and southwards dispersal of Neanderthals during MIS 5. Our analyses are comparable with archaeological and genetic evidence collected during recent decades.},
}

*Neanderthals
Animals
Humans
*Fossils
Archaeology
Geography

@article {pmid39160167,
year = {2024},
author = {Mateo-Lomba, P and Ollé, A and Fernández-Marchena, JL and Saladié, P and Marín, J and Chacón, MG and Vallverdú, J and Cáceres, I},
title = {First identification of a Neanderthal bone spear point through an interdisciplinary analysis at Abric Romaní (NE Iberian Peninsula).},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {19160},
pmid = {39160167},
issn = {2045-2322},
support = {CEX2019-000945-M//Spanish Ministry of Science and Innovation/ ; PID2021-122355NB-C32//MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe/ ; PID2022-138590NB-C41//MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe/ ; SGR 2021 01239//AGAUR/ ; SGR 2021 01237//AGAUR/ ; SGR 2021 01238//AGAUR/ ; 2023PFR-URV-01239//URV/ ; URV, 2023PFR-URV-0127//URV/ ; 2022PFR-URV- 64//URV/ ; 2023PFR-URV-01238//URV/ ; PRE2019-087734//MICINN/ ; ARQ001SOL-201-2022//Departament de Cultura of the Generalitat de Catalunya/ ; CIAPOS/2022/022//Generalitat Valenciana/ ; },
mesh = {Animals ; *Neanderthals/anatomy & histology ; Spain ; *Fossils ; *Bone and Bones/anatomy & histology ; *Archaeology ; Humans ; History, Ancient ; },
abstract = {Osseous industry has been observed at an increasing number of Neanderthal sites. Bone fragments were used for practical purposes, and a range of bone shaping techniques were employed. The variability of bone tools observed in different assemblages reflects considerable functional diversity. However, no bone spear points have been reported from these contexts. A comprehensive analysis of a bone spear point from the Middle Palaeolithic site of Abric Romaní (Barcelona, Spain) is presented. Through an interdisciplinary, multi-technique, and multi-scale approach combining technology, taphonomy, and functional analysis, compelling evidence for manufacture, use, and hafting was uncovered. The specimen exhibits clear signs of intentional knapping. The presence of microscopic linear impact marks, an impact fracture at the tip and potential internal stress fractures indicate its use as a spear. Furthermore, the observed wear pattern and a morphological adjustment of the trabecular tissue support the hafting hypothesis. Abric Romaní contributes to our understanding of Neanderthal hunting behaviour and the significance of composite bone tools in their technological repertoire 50,000 years ago. This discovery highlights the flexibility and adaptability of Neanderthal technology, providing evidence of bone technology that is sometimes obscured in the archaeological record and offering valuable insights into their hunting strategies during the Middle Palaeolithic.},
}

Animals
*Neanderthals/anatomy & histology
Spain
*Fossils
*Bone and Bones/anatomy & histology
*Archaeology
Humans
History, Ancient

@article {pmid39144742,
year = {2024},
author = {Zhao, W},
title = {Reconstructing human history from ancient genomes: an interview with Nobel laureate Svante Pääbo.},
journal = {National science review},
volume = {11},
number = {9},
pages = {nwae120},
doi = {10.1093/nsr/nwae120},
pmid = {39144742},
issn = {2053-714X},
abstract = {Professor Svante Pääbo, Director of the Max Planck Institute for Evolutionary Anthropology, won the Nobel Prize in Physiology or Medicine in 2022 for his discoveries in ancient hominine genomes and human evolution. His pioneering work in sequencing and interpreting the paleo genomes of Neanderthals and Denisovans, as well as their relationship with the modern human genome, was groundbreaking in terms of our understanding of human origins. Nowadays, we can even use commercial kits to easily detect the proportion of Neanderthal genes in our own genomes. Recently, NSR conducted an interview with Professor Pääbo to learn about his interesting work chasing the ancient genomes and reconstructing human evolutionary and migration history from the DNA evidence, as well as his perspective on paleo genome studies and his advice to young researchers: follow your interests and be ready to try some crazy things.},
}

@article {pmid39132848,
year = {2024},
author = {Richards, GD and Jabbour, RS and Guipert, G and Defleur, A},
title = {Early Neanderthal mandibular remains from Baume Moula-Guercy (Soyons, Ardèche).},
journal = {Anatomical record (Hoboken, N.J. : 2007)},
volume = {},
number = {},
pages = {},
doi = {10.1002/ar.25550},
pmid = {39132848},
issn = {1932-8494},
support = {03-Activity-059//Arthur A. Dugoni/ ; },
abstract = {We provide an ontogenetically-based comparative description of mandibular remains from Last Interglacial deposits (MIS 5e) at Baume Moula-Guercy and examine their affinities to European and Middle Eastern Middle-to-Late Pleistocene (≈MIS 14-MIS 1) Homo. Description of the M-G2-419 right partial mandibular corpus with M1-3 (15-16.0 years ±0.5 years) and mandibular fragments M-F4-77 and M-S-TNN1 is with reference to original fossils, casts, CT scans, literature descriptions, and virtual reconstructions. Our comparative sample is ontogenetically based and divided into a Preneanderthal-Neanderthal group and a Homo sapiens group. These groups are subdivided into (1) Preneanderthals (≈MIS 14-9), Early Neanderthals (MIS 7-5e), and Late Neanderthals (MIS 5d-3), and (2) Middle (MIS 5) and Upper (MIS 3-Pre-MIS 1) Paleolithic and recent H. sapiens. Standard techniques were employed for developmental age and sex determinations and measurements. The M-G2-419 mandible possesses corpus features that link it most closely with the Sima de los Huesos Preneanderthal and Early Neanderthal groups. These include mental foramen position, number, and height on the corpus, anterior marginal tubercle position, and mylohyoid line orientation. Metrically, the M-G2-419 mandibular corpus is small relative to adults in all groups, but the thickness/height relationship is like the adult condition. The thickness of the corpus is more like Neanderthal children than adolescents. Molar crown features suggest affinities with the Preneanderthal-Neanderthal group. The Moula-Guercy mandibles possess a combination of Neanderthal-associated features that provides insights into MIS 7-5e paleodeme variation and the timing of appearance of MIS 5d-3 Neanderthal facial features.},
}

@article {pmid39091830,
year = {2024},
author = {Pfennig, A and Lachance, J},
title = {The evolutionary fate of Neanderthal DNA in 30,780 admixed genomes with recent African-like ancestry.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39091830},
issn = {2692-8205},
support = {R35 GM133727/GM/NIGMS NIH HHS/United States ; },
abstract = {Following introgression, Neanderthal DNA was initially purged from non-African genomes, but the evolutionary fate of remaining introgressed DNA has not been explored yet. To fill this gap, we analyzed 30,780 admixed genomes with African-like ancestry from the All of Us research program, in which Neanderthal alleles encountered novel genetic backgrounds during the last 15 generations. Observed amounts of Neanderthal DNA approximately match expectations based on ancestry proportions, suggesting neutral evolution. Nevertheless, we identified genomic regions that have significantly less or more Neanderthal ancestry than expected and are associated with spermatogenesis, innate immunity, and other biological processes. We also identified three novel introgression desert-like regions in recently admixed genomes, whose genetic features are compatible with hybrid incompatibilities and intrinsic negative selection. Overall, we find that much of the remaining Neanderthal DNA in human genomes is not under strong selection, and complex evolutionary dynamics have shaped introgression landscapes in our species.},
}

@article {pmid39032165,
year = {2024},
author = {Seghi, F and Sorrentino, R and Bailey, SE and Piccirilli, E and Vazzana, A and Bortolini, E and Higgins, OA and Marciani, G and Orlando, MA and Spinapolice, EE and Moroni, A and Benazzi, S},
title = {Morphological and morphometric study of the hominin dental casts from Grotta-Riparo di Uluzzo C (Apulia, southern Italy).},
journal = {American journal of biological anthropology},
volume = {185},
number = {1},
pages = {e24998},
doi = {10.1002/ajpa.24998},
pmid = {39032165},
issn = {2692-7691},
support = {European Union - Next Generation EU PRIN 2022 TRAC//European Commission/ ; PNRR PE5 - CHANGES - SPOKE 5//European Commission/ ; European Union - Next Generation EU PRIN 2022 TRACE//European Commission/ ; },
mesh = {Italy ; Animals ; *Fossils ; *Hominidae/anatomy & histology ; Humans ; Tooth, Deciduous/anatomy & histology ; Neanderthals/anatomy & histology ; Tooth/anatomy & histology ; Molar/anatomy & histology ; Paleodontology ; Models, Dental ; },
abstract = {OBJECTIVES: Grotta-Riparo di Uluzzo C (Apulia, southern Italy) is a pivotal site for investigating the evolution of the Middle Paleolithic and the earliest phases of the Upper Paleolithic in southern Italy, as the extensive stratigraphic record of this site includes a thick Mousterian sequence followed by the Uluzzian. Here, we investigate the taxonomic affinity of seven unpublished deciduous human teeth retrieved from the site of Uluzzo C in 1960.

MATERIALS AND METHODS: The teeth are represented by seven plaster dental casts, which are housed at the Museo Civico di Paleontologia e Paletnologia in Maglie (Lecce, Apulia). The location of the original specimens remains unknown, rendering these casts the only human remains evidence yielded by Uluzzo C to date. Based on occlusal-view photographs and digital models of the casts, we examined the external morphology and morphometry of the teeth, comparing them to Homo sapiens and H. neanderthalensis samples. Through geometric morphometric methods and statistical analyses, we analyzed the crown outline of the deciduous molars.

RESULTS: The teeth show morphological and morphometric features that are variably found in H. neanderthalensis, H. sapiens, or both. Specifically, crown outline analysis shows that all molars fall within H. neanderthalensis variability, except for Uluzzo 853 (lower right deciduous first molar), which falls within H. sapiens variability.

DISCUSSION: This study provides the first taxonomic assessment of the hominin teeth from Uluzzo C. The results contribute additional insights into the Paleolithic peopling of southern Italy during a crucial period marked by the persistence of post-Tyrrhenian Neanderthal techno-complexes and the arrival of H. sapiens.},
}

Italy
Animals
*Fossils
*Hominidae/anatomy & histology
Humans
Tooth, Deciduous/anatomy & histology
Neanderthals/anatomy & histology
Tooth/anatomy & histology
Molar/anatomy & histology
Paleodontology
Models, Dental

@article {pmid39029412,
year = {2024},
author = {Dodat, PJ and Albalat, E and Balter, V and Couture-Veschambre, C and Hardy, M and Henrion, J and Holliday, T and Maureille, B},
title = {Diverse bone-calcium isotope compositions in Neandertals suggest different dietary strategies.},
journal = {Journal of human evolution},
volume = {193},
number = {},
pages = {103566},
doi = {10.1016/j.jhevol.2024.103566},
pmid = {39029412},
issn = {1095-8606},
mesh = {Animals ; *Neanderthals ; *Diet ; *Bone and Bones/chemistry ; *Calcium Isotopes/analysis ; France ; Fossils ; },
abstract = {Zooarcheological and geochemical evidence suggests Neanderthals were top predators, but their adherence to a strictly carnivorous diet has been questioned. Recent studies have demonstrated the potential of calcium-stable isotopes to evaluate trophic and ecological relationships. Here, we measure the δ[44/42]Ca values in bone samples from Mousterian contexts at Grotte du Bison (Marine Isotope Stage 3, Yonne, France) and Regourdou (Marine Isotope Stage 5, Dordogne, France) in two new Neanderthal individuals, associated fauna, and living local plants. We use a Bayesian mixing model to estimate the dietary composition of these Neanderthal individuals, plus a third one already analyzed. The results reveal three distinct diets: a diet including accidental or voluntary consumption of bone-based food, an intermediate diet, and a diet without consumption of bone-based food. This finding is the first demonstration of diverse subsistence strategies among Neanderthals and as such, reconciles archaeological and geochemical dietary evidence.},
}

Animals
*Neanderthals
*Diet
*Bone and Bones/chemistry
*Calcium Isotopes/analysis
France
Fossils

@article {pmid39011558,
year = {2024},
author = {Ma, X and Lu, Y and Xu, S},
title = {Adaptive Evolution of Two Distinct Adaptive Haplotypes of Neanderthal Origin at the Immunoglobulin Heavy-chain Locus in East Asian and European Populations.},
journal = {Molecular biology and evolution},
volume = {41},
number = {7},
pages = {},
pmid = {39011558},
issn = {1537-1719},
support = {2023YFC2605400//National Key Research and Development Program of China/ ; 32030020//National Natural Science Foundation of China/ ; //Office of Global Partnerships/ ; //Human Phenome Data Center of Fudan University/ ; },
mesh = {*Neanderthals/genetics ; Animals ; *Haplotypes ; Humans ; Europe ; Asia, Eastern ; Asian People/genetics ; Immunoglobulin Heavy Chains/genetics ; White People/genetics ; Evolution, Molecular ; Genetic Introgression ; Selection, Genetic ; East Asian People ; },
abstract = {Immunoglobulins (Igs) have a crucial role in humoral immunity. Two recent studies have reported a high-frequency Neanderthal-introgressed haplotype throughout Eurasia and a high-frequency Neanderthal-introgressed haplotype specific to southern East Asia at the immunoglobulin heavy-chain (IGH) gene locus on chromosome 14q32.33. Surprisingly, we found the previously reported high-frequency Neanderthal-introgressed haplotype does not exist throughout Eurasia. Instead, our study identified two distinct high-frequency haplotypes of putative Neanderthal origin in East Asia and Europe, although they shared introgressed alleles. Notably, the alleles of putative Neanderthal origin reduced the expression of IGHG1 and increased the expression of IGHG2 and IGHG3 in various tissues. These putatively introgressed alleles also affected the production of IgG1 upon antigen stimulation and increased the risk of systemic lupus erythematosus. Additionally, the greatest genetic differentiation across the whole genome between southern and northern East Asians was observed for the East Asian haplotype of putative Neanderthal origin. The frequency decreased from southern to northern East Asia and correlated positively with the genome-wide proportion of southern East Asian ancestry, indicating that this putative positive selection likely occurred in the common ancestor of southern East Asian populations before the admixture with northern East Asian populations.},
}

*Neanderthals/genetics
Animals
*Haplotypes
Humans
Europe
Asia, Eastern
Asian People/genetics
Immunoglobulin Heavy Chains/genetics
White People/genetics
Evolution, Molecular
Genetic Introgression
Selection, Genetic
East Asian People

@article {pmid38997559,
year = {2024},
author = {Eisenstein, M},
title = {Neanderthal-human baby-making was recent - and brief.},
journal = {Nature},
volume = {},
number = {},
pages = {},
doi = {10.1038/d41586-024-01452-3},
pmid = {38997559},
issn = {1476-4687},
}

@article {pmid38991054,
year = {2024},
author = {Li, L and Comi, TJ and Bierman, RF and Akey, JM},
title = {Recurrent gene flow between Neanderthals and modern humans over the past 200,000 years.},
journal = {Science (New York, N.Y.)},
volume = {385},
number = {6705},
pages = {eadi1768},
doi = {10.1126/science.adi1768},
pmid = {38991054},
issn = {1095-9203},
mesh = {Animals ; Humans ; *Gene Flow ; Genetic Introgression ; *Genome, Human ; *Neanderthals/genetics ; Population Density ; Whole Genome Sequencing ; Extinction, Biological ; },
abstract = {Although it is well known that the ancestors of modern humans and Neanderthals admixed, the effects of gene flow on the Neanderthal genome are not well understood. We develop methods to estimate the amount of human-introgressed sequences in Neanderthals and apply it to whole-genome sequence data from 2000 modern humans and three Neanderthals. We estimate that Neanderthals have 2.5 to 3.7% human ancestry, and we leverage human-introgressed sequences in Neanderthals to revise estimates of Neanderthal ancestry in modern humans, show that Neanderthal population sizes were significantly smaller than previously estimated, and identify two distinct waves of modern human gene flow into Neanderthals. Our data provide insights into the genetic legacy of recurrent gene flow between modern humans and Neanderthals.},
}

Animals
Humans
*Gene Flow
Genetic Introgression
*Genome, Human
*Neanderthals/genetics
Population Density
Whole Genome Sequencing
Extinction, Biological

@article {pmid38956433,
year = {2024},
author = {Yaghmouri, M and Safdari Lord, J and Amini, M and Yekaninejad, MS and Izadi, P},
title = {The association of rs17713054 with Neanderthal origin at 3p21.31 locus with the severity of COVID-19 in Iranian patients.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {15058},
pmid = {38956433},
issn = {2045-2322},
support = {58558//Tehran University of Medical Sciences/ ; },
mesh = {Humans ; *COVID-19/genetics/virology/epidemiology ; Iran/epidemiology ; *Neanderthals/genetics ; Male ; Female ; *Polymorphism, Single Nucleotide ; Middle Aged ; *Severity of Illness Index ; *Genetic Predisposition to Disease ; Animals ; *SARS-CoV-2/genetics/isolation & purification ; Adult ; Haplotypes ; Chromosomes, Human, Pair 3/genetics ; Alleles ; Genome-Wide Association Study ; Genotype ; Aged ; },
abstract = {Since the COVID-19 pandemic, the diversity of clinical manifestations in patients has been a tremendous challenge. It seems that genetic variations, as one of the players, contribute to the variety of symptoms. Genome-wide association studies have demonstrated the influence of certain genomic regions on the disease prognosis. Particularly, a haplotype at 3p21.31 locus, inherited from Neanderthals, showed an association with COVID-19 severity. Despite several studies regarding this haplotype, some key variants are not sufficiently addressed. In the present study, we investigated the association of rs17713054 at 3p21.31 with COVID-19 severity. We analyzed the genotype of 251 Iranian COVID-19 patients (151 patients with asymptomatic to mild form as control and 100 patients with severe to critical symptoms without any comorbidities as case group) using the ARMS-PCR method. Results demonstrated that the A allele confers an almost twofold increased risk for COVID-19 severity (P value = 0.008). The AA genotype also raises the risk by more than 11 times following the recessive model (P value = 0.013). In conclusion, the A allele in rs17713054 was a risk allele in Iranian patients and was independently associated with COVID-19 severity. More studies are beneficial to confirm these findings in other populations and to develop strategies for risk assessment, prevention, and personalized medicine.},
}

Humans
*COVID-19/genetics/virology/epidemiology
Iran/epidemiology
*Neanderthals/genetics
Male
Female
*Polymorphism, Single Nucleotide
Middle Aged
*Severity of Illness Index
*Genetic Predisposition to Disease
Animals
*SARS-CoV-2/genetics/isolation & purification
Adult
Haplotypes
Chromosomes, Human, Pair 3/genetics
Alleles
Genome-Wide Association Study
Genotype
Aged

@article {pmid38932149,
year = {2024},
author = {Ferreira, RC and Alves, GV and Ramon, M and Antoneli, F and Briones, MRS},
title = {Reconstructing Prehistoric Viral Genomes from Neanderthal Sequencing Data.},
journal = {Viruses},
volume = {16},
number = {6},
pages = {},
pmid = {38932149},
issn = {1999-4915},
support = {20/08943-5//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 311154/2021-2//National Council for Scientific and Technological Development/ ; },
mesh = {Animals ; *Neanderthals/genetics/virology ; *Genome, Viral ; *DNA, Ancient/analysis ; Evolution, Molecular ; DNA, Viral/genetics ; Sequence Analysis, DNA/methods ; Humans ; Phylogeny ; DNA Viruses/genetics/classification/isolation & purification ; Fossils/virology ; },
abstract = {DNA viruses that produce persistent infections have been proposed as potential causes for the extinction of Neanderthals, and, therefore, the identification of viral genome remnants in Neanderthal sequence reads is an initial step to address this hypothesis. Here, as proof of concept, we searched for viral remnants in sequence reads of Neanderthal genome data by mapping to adenovirus, herpesvirus and papillomavirus, which are double-stranded DNA viruses that may establish lifelong latency and can produce persistent infections. The reconstructed ancient viral genomes of adenovirus, herpesvirus and papillomavirus revealed conserved segments, with nucleotide identity to extant viral genomes and variable regions in coding regions with substantial divergence to extant close relatives. Sequence reads mapped to extant viral genomes showed deamination patterns of ancient DNA, and these ancient viral genomes showed divergence consistent with the age of these samples (≈50,000 years) and viral evolutionary rates (10[-5] to 10[-8] substitutions/site/year). Analysis of random effects showed that the Neanderthal mapping to genomes of extant persistent viruses is above what is expected by random similarities of short reads. Also, negative control with a nonpersistent DNA virus does not yield statistically significant assemblies. This work demonstrates the feasibility of identifying viral genome remnants in archaeological samples with signal-to-noise assessment.},
}

Animals
*Neanderthals/genetics/virology
*Genome, Viral
*DNA, Ancient/analysis
Evolution, Molecular
DNA, Viral/genetics
Sequence Analysis, DNA/methods
Humans
Phylogeny
DNA Viruses/genetics/classification/isolation & purification
Fossils/virology

@article {pmid38924400,
year = {2024},
author = {Conde-Valverde, M and Quirós-Sánchez, A and Diez-Valero, J and Mata-Castro, N and García-Fernández, A and Quam, R and Carretero, JM and García-González, R and Rodríguez, L and Sánchez-Andrés, Á and Arsuaga, JL and Martínez, I and Villaverde, V},
title = {The child who lived: Down syndrome among Neanderthals?.},
journal = {Science advances},
volume = {10},
number = {26},
pages = {eadn9310},
pmid = {38924400},
issn = {2375-2548},
mesh = {*Down Syndrome/psychology ; Humans ; Animals ; *Neanderthals ; Child ; Female ; Male ; Child, Preschool ; },
abstract = {Caregiving for disabled individuals among Neanderthals has been known for a long time, and there is a debate about the implications of this behavior. Some authors believe that caregiving took place between individuals able to reciprocate the favor, while others argue that caregiving was produced by a feeling of compassion related to other highly adaptive prosocial behaviors. The study of children with severe pathologies is particularly interesting, as children have a very limited possibility to reciprocate the assistance. We present the case of a Neanderthal child who suffered from a congenital pathology of the inner ear, probably debilitating, and associated with Down syndrome. This child would have required care for at least 6 years, likely necessitating other group members to assist the mother in childcare.},
}

*Down Syndrome/psychology
Humans
Animals
*Neanderthals
Child
Female
Male
Child, Preschool

@article {pmid38916350,
year = {2024},
author = {Sankaranarayanan, G and Kodiveri Muthukaliannan, G},
title = {Exploring antimicrobial resistance determinants in the Neanderthal microbiome.},
journal = {Microbiology spectrum},
volume = {12},
number = {8},
pages = {e0266223},
pmid = {38916350},
issn = {2165-0497},
support = {20/2022-ECR-II//Indian Council of Medical Research (ICMR)/ ; },
mesh = {Animals ; *Microbiota/genetics/drug effects ; *Neanderthals/genetics/microbiology ; *DNA, Ancient/analysis ; *Metagenomics ; *Bacteria/genetics/drug effects/classification/isolation & purification ; *Anti-Bacterial Agents/pharmacology ; Drug Resistance, Bacterial/genetics ; Humans ; Feces/microbiology ; Metagenome ; Drug Resistance, Microbial/genetics ; Europe ; Fossils/microbiology ; },
abstract = {UNLABELLED: This study aimed to investigate the presence of antimicrobial resistance determinants (ARDs) in the Neanderthal microbiome through meticulous analysis of metagenomic data derived directly from dental calculus and fecal sediments across diverse Neanderthal sites in Europe. Employing a targeted locus mapping approach followed by a consensus strategy instead of an assembly-first approach, we aimed to identify and characterize ARDs within these ancient microbial communities. A comprehensive and redundant ARD database was constructed by amalgamating data from various antibiotic resistance gene repositories. Our results highlighted the efficacy of the KMA tool in providing a robust alignment of ancient metagenomic reads to the antibiotic resistance gene database. Notably, the KMA tool identified a limited number of ARDs, with only the 23S ribosomal gene from the dental calculus sample of Neanderthal remains at Goyet Troisieme Caverne exhibiting ancient DNA (aDNA) characteristics. Despite not identifying ARDs with typical ancient DNA damage patterns or negative distance proportions, our findings suggest a nuanced identification of putative antimicrobial resistance determinants in the Neanderthal microbiome's genetic repertoire based on the taxonomy-habitat correlation. Nevertheless, our findings are limited by factors such as environmental DNA contamination, DNA fragmentation, and cytosine deamination of aDNA. The study underscores the necessity for refined methodologies to unlock the genomic assets of prehistoric populations, fostering a comprehensive understanding of the intricate dynamics shaping the microbial landscape across history.

IMPORTANCE: The results of our analysis demonstrate the challenges in identifying determinants of antibiotic resistance within the endogenous microbiome of Neanderthals. Despite the comprehensive investigation of multiple studies and the utilization of advanced analytical techniques, the detection of antibiotic resistance determinants in the ancient microbial communities proved to be particularly difficult. However, our analysis did reveal the presence of some authentic ancient conservative genes, indicating the preservation of certain genetic elements over time. These findings raise intriguing questions about the factors influencing the presence or absence of antibiotic resistance in ancient microbial communities. It could be speculated that the spread of current antibiotic resistance, which has reached alarming levels in modern times, is primarily driven by anthropogenic factors such as the widespread use and misuse of antibiotics in medical and agricultural practices.},
}

Animals
*Microbiota/genetics/drug effects
*Neanderthals/genetics/microbiology
*DNA, Ancient/analysis
*Metagenomics
*Bacteria/genetics/drug effects/classification/isolation & purification
*Anti-Bacterial Agents/pharmacology
Drug Resistance, Bacterial/genetics
Humans
Feces/microbiology
Metagenome
Drug Resistance, Microbial/genetics
Europe
Fossils/microbiology

@article {pmid38889149,
year = {2024},
author = {Yermakovich, D and André, M and Brucato, N and Kariwiga, J and Leavesley, M and Pankratov, V and Mondal, M and Ricaut, FX and Dannemann, M},
title = {Denisovan admixture facilitated environmental adaptation in Papua New Guinean populations.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {26},
pages = {e2405889121},
pmid = {38889149},
issn = {1091-6490},
support = {TK214//HM | Estonian Research Competency Council (Research Competency Council)/ ; 810645//EC | Horizon Europe | WPSERA | HORIZON EUROPE Reforming and enhancing the European Research and Innovation system (REERIS)/ ; MOBEC008//EC | European Regional Development Fund (ERDF)/ ; PAPUAEVOL 20-CE12-0003-01//Association Nationale de la Recherche et de la Technologie (ANRT)/ ; NA//French Ministry of Foreign and European Affairs/ ; NA//Laboratoire d'Excellence TULIP (Labex TULIP)/ ; NA//Leakey Foundation (The Leakey Foundation)/ ; },
mesh = {Papua New Guinea ; Humans ; Animals ; *Haplotypes ; *Neanderthals/genetics ; Adaptation, Physiological/genetics ; Genetics, Population ; },
abstract = {Neandertals and Denisovans, having inhabited distinct regions in Eurasia and possibly Oceania for over 200,000 y, experienced ample time to adapt to diverse environmental challenges these regions presented. Among present-day human populations, Papua New Guineans (PNG) stand out as one of the few carrying substantial amounts of both Neandertal and Denisovan DNA, a result of past admixture events with these archaic human groups. This study investigates the distribution of introgressed Denisovan and Neandertal DNA within two distinct PNG populations, residing in the highlands of Mt Wilhelm and the lowlands of Daru Island. These locations exhibit unique environmental features, some of which may parallel the challenges that archaic humans once confronted and adapted to. Our results show that PNG highlanders carry higher levels of Denisovan DNA compared to PNG lowlanders. Among the Denisovan-like haplotypes with higher frequencies in highlander populations, those exhibiting the greatest frequency difference compared to lowlander populations also demonstrate more pronounced differences in population frequencies than frequency-matched nonarchaic variants. Two of the five most highly differentiated of those haplotypes reside in genomic areas linked to brain development genes. Conversely, Denisovan-like haplotypes more frequent in lowlanders overlap with genes associated with immune response processes. Our findings suggest that Denisovan DNA has provided genetic variation associated with brain biology and immune response to PNG genomes, some of which might have facilitated adaptive processes to environmental challenges.},
}

Papua New Guinea
Humans
Animals
*Haplotypes
*Neanderthals/genetics
Adaptation, Physiological/genetics
Genetics, Population

@article {pmid38840007,
year = {2024},
author = {Callaway, E},
title = {These Neanderthal fire pits offer an extraordinarily precise snapshot of ancient life.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {38840007},
issn = {1476-4687},
}

@article {pmid38802968,
year = {2024},
author = {Roca-Ayats, N and Maceda, I and Bruque, CD and Martínez-Gil, N and Garcia-Giralt, N and Cozar, M and Mellibovsky, L and Van Hul, W and Lao, O and Grinberg, D and Balcells, S},
title = {Evolutionary and functional analyses of LRP5 in archaic and extant modern humans.},
journal = {Human genomics},
volume = {18},
number = {1},
pages = {53},
pmid = {38802968},
issn = {1479-7364},
support = {SAF 2016-75948R and PID2019-107188RB-C21//Ministerio de Ciencia e Innovación/ ; GRC 2017 SGR 937//Generalitat de Catalunya/ ; 2017SGR:00738//Catalan Government/ ; PGC2018-098574-B-I00//Ministerio de Economía y Competitividad/ ; },
mesh = {Humans ; *Low Density Lipoprotein Receptor-Related Protein-5/genetics ; *Evolution, Molecular ; Animals ; *Neanderthals/genetics ; Selection, Genetic/genetics ; Hominidae/genetics ; Haplotypes/genetics ; Bone Density/genetics ; Genome, Human/genetics ; },
abstract = {BACKGROUND: The human lineage has undergone a postcranial skeleton gracilization (i.e. lower bone mass and strength relative to body size) compared to other primates and archaic populations such as the Neanderthals. This gracilization has been traditionally explained by differences in the mechanical load that our ancestors exercised. However, there is growing evidence that gracilization could also be genetically influenced.

RESULTS: We have analyzed the LRP5 gene, which is known to be associated with high bone mineral density conditions, from an evolutionary and functional point of view. Taking advantage of the published genomes of archaic Homo populations, our results suggest that this gene has a complex evolutionary history both between archaic and living humans and within living human populations. In particular, we identified the presence of different selective pressures in archaics and extant modern humans, as well as evidence of positive selection in the African and South East Asian populations from the 1000 Genomes Project. Furthermore, we observed a very limited evidence of archaic introgression in this gene (only at three haplotypes of East Asian ancestry out of the 1000 Genomes), compatible with a general erasing of the fingerprint of archaic introgression due to functional differences in archaics compared to extant modern humans. In agreement with this hypothesis, we observed private mutations in the archaic genomes that we experimentally validated as putatively increasing bone mineral density. In particular, four of five archaic missense mutations affecting the first β-propeller of LRP5 displayed enhanced Wnt pathway activation, of which two also displayed reduced negative regulation.

CONCLUSIONS: In summary, these data suggest a genetic component contributing to the understanding of skeletal differences between extant modern humans and archaic Homo populations.},
}

Humans
*Low Density Lipoprotein Receptor-Related Protein-5/genetics
*Evolution, Molecular
Animals
*Neanderthals/genetics
Selection, Genetic/genetics
Hominidae/genetics
Haplotypes/genetics
Bone Density/genetics
Genome, Human/genetics

@article {pmid38798350,
year = {2024},
author = {Iasi, LNM and Chintalapati, M and Skov, L and Mesa, AB and Hajdinjak, M and Peter, BM and Moorjani, P},
title = {Neandertal ancestry through time: Insights from genomes of ancient and present-day humans.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {38798350},
issn = {2692-8205},
support = {R35 GM142978/GM/NIGMS NIH HHS/United States ; },
abstract = {Gene flow from Neandertals has shaped the landscape of genetic and phenotypic variation in modern humans. We identify the location and size of introgressed Neandertal ancestry segments in more than 300 genomes spanning the last 50,000 years. We study how Neandertal ancestry is shared among individuals to infer the time and duration of the Neandertal gene flow. We find the correlation of Neandertal segment locations across individuals and their divergence to sequenced Neandertals, both support a model of single major Neandertal gene flow. Our catalog of introgressed segments through time confirms that most natural selection-positive and negative-on Neandertal ancestry variants occurred immediately after the gene flow, and provides new insights into how the contact with Neandertals shaped human origins and adaptation.},
}

@article {pmid38782948,
year = {2024},
author = {Limmer, LS and Santon, M and McGrath, K and Harvati, K and El Zaatari, S},
title = {Differences in childhood stress between Neanderthals and early modern humans as reflected by dental enamel growth disruptions.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {11293},
pmid = {38782948},
issn = {2045-2322},
support = {353106138//Deutsche Forschungsgemeinschaft/ ; EP/X020819/1//Engineering and Physical Sciences Research Council/ ; State Research Award 2014//Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg/ ; 101019659//H2020 European Research Council/ ; 101001889//H2020 European Research Council/ ; },
mesh = {Animals ; *Neanderthals ; Humans ; *Dental Enamel/growth & development ; Child ; *Dental Enamel Hypoplasia ; Bayes Theorem ; Child, Preschool ; Male ; Fossils ; Female ; Stress, Physiological ; Infant ; },
abstract = {Neanderthals' lives were historically portrayed as highly stressful, shaped by constant pressures to survive in harsh ecological conditions, thus potentially contributing to their extinction. Recent work has challenged this interpretation, leaving the issue of stress among Paleolithic populations highly contested and warranting in-depth examination. Here, we analyze the frequency of dental enamel hypoplasia, a growth disruption indicator of early life stress, in the largest sample of Neanderthal and Upper Paleolithic dentitions investigated to date for these features. To track potential species-specific patterns in the ontogenetic distribution of childhood stress, we present the first comprehensive Bayesian modelling of the likelihood of occurrence of individual and matched enamel growth disruptions throughout ontogeny. Our findings support similar overall stress levels in both groups but reveal species-specific patterns in its ontogenetic distribution. While Neanderthal children faced increasing likelihoods of growth disruptions starting with the weaning process and culminating in intensity post-weaning, growth disruptions in Upper Paleolithic children were found to be limited around the period of weaning and substantially dropping after its expected completion. These results might, at least in part, reflect differences in childcare or other behavioral strategies between the two taxa, including those that were advantageous for modern humans' long-term survival.},
}

Animals
*Neanderthals
Humans
*Dental Enamel/growth & development
Child
*Dental Enamel Hypoplasia
Bayes Theorem
Child, Preschool
Male
Fossils
Female
Stress, Physiological
Infant

@article {pmid38782905,
year = {2024},
author = {Yee, SW and Ferrández-Peral, L and Alentorn-Moron, P and Fontsere, C and Ceylan, M and Koleske, ML and Handin, N and Artegoitia, VM and Lara, G and Chien, HC and Zhou, X and Dainat, J and Zalevsky, A and Sali, A and Brand, CM and Wolfreys, FD and Yang, J and Gestwicki, JE and Capra, JA and Artursson, P and Newman, JW and Marquès-Bonet, T and Giacomini, KM},
title = {Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {4380},
pmid = {38782905},
issn = {2041-1723},
support = {GM117163//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01 EY032161/EY/NEI NIH HHS/United States ; R01 GM139875/GM/NIGMS NIH HHS/United States ; GM139875//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01 GM117163/GM/NIGMS NIH HHS/United States ; EY032161//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; },
mesh = {Animals ; Humans ; Amino Acid Sequence ; Estradiol/metabolism ; HEK293 Cells ; Hominidae/genetics/metabolism ; Mutation, Missense ; Organic Cation Transport Proteins/metabolism/genetics ; *Primates/genetics ; Pseudogenes ; Substrate Specificity ; },
abstract = {SLC22A10 is an orphan transporter with unknown substrates and function. The goal of this study is to elucidate its substrate specificity and functional characteristics. In contrast to orthologs from great apes, human SLC22A10, tagged with green fluorescent protein, is not expressed on the plasma membrane. Cells expressing great ape SLC22A10 orthologs exhibit significant accumulation of estradiol-17β-glucuronide, unlike those expressing human SLC22A10. Sequence alignments reveal a proline at position 220 in humans, which is a leucine in great apes. Replacing proline with leucine in SLC22A10-P220L restores plasma membrane localization and uptake function. Neanderthal and Denisovan genomes show proline at position 220, akin to modern humans, indicating functional loss during hominin evolution. Human SLC22A10 is a unitary pseudogene due to a fixed missense mutation, P220, while in great apes, its orthologs transport sex steroid conjugates. Characterizing SLC22A10 across species sheds light on its biological role, influencing organism development and steroid homeostasis.},
}

Animals
Humans
Amino Acid Sequence
Estradiol/metabolism
HEK293 Cells
Hominidae/genetics/metabolism
Mutation, Missense
Organic Cation Transport Proteins/metabolism/genetics
*Primates/genetics
Pseudogenes
Substrate Specificity

@article {pmid38779339,
year = {2024},
author = {Gennai, J},
title = {The Mousterian in North-Western Tuscany: publishing fieldwork documentation leads to a new stratigraphical interpretation of the Piano di Mommio sites.},
journal = {Open research Europe},
volume = {4},
number = {},
pages = {37},
pmid = {38779339},
issn = {2732-5121},
abstract = {BACKGROUND: The Mousterian technocomplex is commonly associated with Neanderthals and therefore serves as a proxy for their presence across Europe. Stratified archaeological sites are the most informative because they can yield information about artefacts' spatial distribution and dating. Only a few of the Mousterian sites in Tuscany (Italy) met these conditions and most of these sites are concentrated in the North-Western area, with three specific sites situated in proximity to the village of Piano di Mommio, on the slopes of a small river canyon. Nevertheless, research on the sites stopped early on due to their small extent and complete excavation, which does not allow for additional fieldwork.

METHODS: This article presents previously unpublished field notes, reports, and images, which are then correlated with recent archaeological surveys.

RESULTS: This combination of historical and contemporary data aims to provide a more detailed understanding of the context in which the assemblages at these sites were found. The insights gained from this research shed light on the arrangement and positioning of artefacts at these locations, offering valuable information to guide future investigations on the assemblages.

CONCLUSIONS: The proposed stratigraphical interpretation adheres to the available information and therefore contributes to a future baseline for new research on the sites and on Neanderthal presence in the area.},
}

@article {pmid38778167,
year = {2024},
author = {Marinelli, F and Moncel, MH and Lemorini, C},
title = {The use of bones as tools in Late Lower Paleolithic of Central Italy.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {11666},
pmid = {38778167},
issn = {2045-2322},
support = {ANR-19-CE27-0011-01//Neandroots project/ ; },
mesh = {Italy ; Animals ; *Fossils ; *Bone and Bones ; *Archaeology ; Humans ; Neanderthals ; Hominidae ; History, Ancient ; Tool Use Behavior ; },
abstract = {The Latium area in Italy has yielded rich evidence of Lower Paleolithic sites with both faunal remains, artefacts, and human fossil remains, such as the Ceprano human skull. Many are the sites where lithic industry has been found in association with bone industry. Medium and large animals were a key resource because they provided an enormous amount of meat and fat. However, they were extensively exploited for their bones, rich in marrow, and as raw material for tool production. Bone tools are so far few documented for early period of time and especially for the Middle Pleistocene in Western Europe. We report here evidence of bone tools and their efficiency of use for hominin groups living in the Frosinone-Ceprano basin during the MIS 11/10, a key period which records behavioral innovations and onset of the Neanderthal behaviors. In three sites, Isoletta, Colle Avarone and Selvotta, several bone tools and bone flakes have been discovered (MIS 11/10). They were associated to stone artefacts part of the hominins tool-kit. Technological and use-wear analyses conducted on these bone industries, dated between 410 and 430 ka, yield relevant results to understand the effectiveness of the bones tools found associated with lithic series, including handaxes.},
}

Italy
Animals
*Fossils
*Bone and Bones
*Archaeology
Humans
Neanderthals
Hominidae
History, Ancient
Tool Use Behavior

@article {pmid38771659,
year = {2024},
author = {Hubáček, JA and Šedová, L and Hellerová, V and Adámková, V and Tóthová, V},
title = {Increased prevalence of the COVID-19 associated Neanderthal mutations in the Central European Roma population.},
journal = {Annals of human biology},
volume = {51},
number = {1},
pages = {2341727},
doi = {10.1080/03014460.2024.2341727},
pmid = {38771659},
issn = {1464-5033},
mesh = {Humans ; *COVID-19/genetics/epidemiology ; *Roma/genetics ; Male ; *SARS-CoV-2 ; Female ; Animals ; *Neanderthals/genetics ; Mutation ; Middle Aged ; Czech Republic/epidemiology ; Adult ; Prevalence ; 2',5'-Oligoadenylate Synthetase/genetics ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; Transcription Factors/genetics ; Aged ; },
abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent COVID-19 has spread world-wide and become pandemic with about 7 million deaths reported so far. Interethnic variability of the disease has been described, but a significant part of the differences remain unexplained and may be attributable to genetic factors.

AIM: To analyse genetic factors potentially influencing COVID-19 susceptibility and severity in European Roma minority.

SUBJECTS AND METHODS: Two genetic determinants, within OAS-1 (2-prime,5-prime-oligoadenylate synthetase 1, a key protein in the defence against viral infection; it activates RNases that degrade viral RNAs; rs4767027 has been analysed) and LZTFL1 (leucine zipper transcription factor-like 1, expressed in the lung respiratory epithelium; rs35044562 has been analysed) genes were screened in a population-sample of Czech Roma (N = 302) and majority population (N = 2,559).

RESULTS: For both polymorphisms, Roma subjects were more likely carriers of at least one risky allele for both rs4767027-C (p < 0.001) and rs35044562-G (p < 0.00001) polymorphism. There were only 5.3% Roma subjects without at least one risky allele in comparison with 10.1% in the majority population (p < 0.01).

CONCLUSIONS: It is possible that different genetic background plays an important role in increased prevalence of COVID-19 in the Roma minority.},
}

Humans
*COVID-19/genetics/epidemiology
*Roma/genetics
Male
*SARS-CoV-2
Female
Animals
*Neanderthals/genetics
Mutation
Middle Aged
Czech Republic/epidemiology
Adult
Prevalence
2',5'-Oligoadenylate Synthetase/genetics
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
Transcription Factors/genetics
Aged

@article {pmid38760502,
year = {2024},
author = {Pauly, R and Johnson, L and Feltus, FA and Casanova, EL},
title = {Enrichment of a subset of Neanderthal polymorphisms in autistic probands and siblings.},
journal = {Molecular psychiatry},
volume = {29},
number = {11},
pages = {3452-3461},
pmid = {38760502},
issn = {1476-5578},
mesh = {Animals ; Female ; Humans ; Male ; *Autistic Disorder/genetics ; Genetic Association Studies/methods ; *Genetic Predisposition to Disease ; Genome, Human ; Genotype ; Hispanic or Latino/genetics ; *Neanderthals/genetics ; *Polymorphism, Single Nucleotide ; *Siblings ; United States ; White/genetics ; Black or African American/genetics ; },
abstract = {Homo sapiens and Neanderthals underwent hybridization during the Middle/Upper Paleolithic age, culminating in retention of small amounts of Neanderthal-derived DNA in the modern human genome. In the current study, we address the potential roles Neanderthal single nucleotide polymorphisms (SNP) may be playing in autism susceptibility in samples of black non-Hispanic, white Hispanic, and white non-Hispanic people using data from the Simons Foundation Powering Autism Research (SPARK), Genotype-Tissue Expression (GTEx), and 1000 Genomes (1000G) databases. We have discovered that rare variants are significantly enriched in autistic probands compared to race-matched controls. In addition, we have identified 25 rare and common SNPs that are significantly enriched in autism on different ethnic backgrounds, some of which show significant clinical associations. We have also identified other SNPs that share more specific genotype-phenotype correlations but which are not necessarily enriched in autism and yet may nevertheless play roles in comorbid phenotype expression (e.g., intellectual disability, epilepsy, and language regression). These results strongly suggest Neanderthal-derived DNA is playing a significant role in autism susceptibility across major populations in the United States.},
}

Animals
Female
Humans
Male
*Autistic Disorder/genetics
Genetic Association Studies/methods
*Genetic Predisposition to Disease
Genome, Human
Genotype
Hispanic or Latino/genetics
*Neanderthals/genetics
*Polymorphism, Single Nucleotide
*Siblings
United States
White/genetics
Black or African American/genetics

@article {pmid38739836,
year = {2024},
author = {Helmbrecht, N and Lackner, M and Maricic, T and Pääbo, S},
title = {The modern human aryl hydrocarbon receptor is more active when ancestralized by genome editing.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {22},
pages = {e2402159121},
pmid = {38739836},
issn = {1091-6490},
support = {PAABO//NOMIS Stiftung (NOMIS Foundation)/ ; },
mesh = {*Receptors, Aryl Hydrocarbon/genetics/metabolism ; Humans ; *Gene Editing/methods ; Animals ; *Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; Evolution, Molecular ; Pan troglodytes/genetics ; Neanderthals/genetics ; Ligands ; },
abstract = {The aryl hydrocarbon receptor (AHR) is a transcription factor that has many functions in mammals. Its best known function is that it binds aromatic hydrocarbons and induces the expression of cytochrome P450 genes, which encode enzymes that metabolize aromatic hydrocarbons and other substrates. All present-day humans carry an amino acid substitution at position 381 in the AHR that occurred after the divergence of modern humans from Neandertals and Denisovans. Previous studies that have expressed the ancestral and modern versions of AHR from expression vectors have yielded conflicting results with regard to their activities. Here, we use genome editing to modify the endogenous AHR gene so that it encodes to the ancestral, Neandertal-like AHR protein in human cells. In the absence of exogenous ligands, the expression of AHR target genes is higher in cells expressing the ancestral AHR than in cells expressing the modern AHR, and similar to the expression in chimpanzee cells. Furthermore, the modern human AHR needs higher doses of three ligands than the ancestral AHR to induce the expression of target genes. Thus, the ability of AHR to induce the expression of many of its target genes is reduced in modern humans.},
}

*Receptors, Aryl Hydrocarbon/genetics/metabolism
Humans
*Gene Editing/methods
Animals
*Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism
Evolution, Molecular
Pan troglodytes/genetics
Neanderthals/genetics
Ligands

@article {pmid38714790,
year = {2024},
author = {Schmidt, P and Tennie, C},
title = {Problems with two recent Petri net analyses of Neanderthal adhesive technology.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {10481},
pmid = {38714790},
issn = {2045-2322},
}

@article {pmid38714734,
year = {2024},
author = {Fajardo, S and Kozowyk, PRB and Langejans, GHJ},
title = {Reply to: Problems with two recent Petri net analyses of Neanderthal adhesive technology.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {10489},
pmid = {38714734},
issn = {2045-2322},
support = {804151//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; },
}

@article {pmid38683367,
year = {2024},
author = {Mansueto, A and Good, DJ},
title = {Conservation of a Chromosome 8 Inversion and Exon Mutations Confirm Common Gulonolactone Oxidase Gene Evolution Among Primates, Including H. Neanderthalensis.},
journal = {Journal of molecular evolution},
volume = {92},
number = {3},
pages = {266-277},
pmid = {38683367},
issn = {1432-1432},
mesh = {Animals ; *Evolution, Molecular ; *Exons/genetics ; *Phylogeny ; *Primates/genetics ; *Mutation/genetics ; Humans ; *L-Gulonolactone Oxidase/genetics ; *Chromosome Inversion/genetics ; Pseudogenes/genetics ; Conserved Sequence/genetics ; },
abstract = {Ascorbic acid functions as an antioxidant and facilitates other biochemical processes such as collagen triple helix formation, and iron uptake by cells. Animals which endogenously produce ascorbic acid have a functional gulonolactone oxidase gene (GULO); however, humans have a GULO pseudogene (GULOP) and depend on dietary ascorbic acid. In this study, the conservation of GULOP sequences in the primate haplorhini suborder were investigated and compared to the GULO sequences belonging to the primates strepsirrhini suborder. Phylogenetic analysis suggested that the conserved GULOP exons in the haplorhini primates experienced a high rate of mutations following the haplorhini/strepsirrhini divergence. This high mutation rate has decreased during the evolution of the haplorhini primates. Additionally, indels of the haplorhini GULOP sequences were conserved across the suborder. A separate analysis for GULO sequences and well-conserved GULOP sequences focusing on placental mammals identified an in-frame GULO sequence in the Brazilian guinea pig, and a potential GULOP sequence in the pika. Similar to haplorhini primates, the guinea pig and lagomorph species have experienced a high substitution rate when compared to the mammals used in this study. A shared synteny to examine the conservation of local genes near GULO/GULOP identified a conserved inversion around the GULO/GULOP locus between the haplorhini and strepsirrhini primates. Fischer's exact test did not support an association between GULOP and the chromosomal inversion. Mauve alignment showed that the inversion of the length of the syntenic block that the GULO/GULOP genes belonged to was variable. However, there were frequent rearrangements around ~ 2 million base pairs adjacent to GULOP involving the KIF13B and MSRA genes. These data may suggest that genes acquiring deleterious mutations in the coding sequence may respond to these deleterious mutations with rapid substitution rates.},
}

Animals
*Evolution, Molecular
*Exons/genetics
*Phylogeny
*Primates/genetics
*Mutation/genetics
Humans
*L-Gulonolactone Oxidase/genetics
*Chromosome Inversion/genetics
Pseudogenes/genetics
Conserved Sequence/genetics

@article {pmid38658463,
year = {2024},
author = {Yousfi, FZE and Haroun, AE and Nebhani, C and Belayachi, J and Askander, O and Fahime, EE and Fares, H and Ennibi, K and Abouqal, R and Razine, R and Bouhouche, A},
title = {Prevalence of the protective OAS1 rs10774671-G allele against severe COVID-19 in Moroccans: implications for a North African Neanderthal connection.},
journal = {Archives of virology},
volume = {169},
number = {5},
pages = {109},
pmid = {38658463},
issn = {1432-8798},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *2',5'-Oligoadenylate Synthetase/genetics ; Africa, Northern ; Alleles ; *COVID-19/genetics/virology/epidemiology ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; North African People ; *Polymorphism, Single Nucleotide ; Prevalence ; },
abstract = {The clinical presentation of COVID-19 shows high variability among individuals, which is partly due to genetic factors. The OAS1/2/3 cluster has been found to be strongly associated with COVID-19 severity. We examined this locus in the Moroccan population for the occurrence of the critical variant rs10774671 and its respective haplotype blocks. The frequency of single-nucleotide polymorphisms (SNPs) in the cluster of OAS immunity genes in 157 unrelated individuals of Moroccan origin was determined using an in-house exome database. OAS1 exon 6 of 71 SARS-CoV-2-positive individuals with asymptomatic/mild disease and 74 with moderate/severe disease was sequenced by the Sanger method. The genotypic, allelic, and haplotype frequencies of three SNPs were compared between these two groups. Finally, males in our COVID-19 series were genotyped for the Berber-specific marker E-M81. The prevalence of the OAS1 rs10774671-G allele in present-day Moroccans was found to be 40.4%, which is similar to that found in Europeans. However, it was found equally in both the Neanderthal GGG haplotype and the African GAC haplotype, with a frequency of 20% each. These two haplotypes, and hence the rs10774671-G allele, were significantly associated with protection against severe COVID-19 (p = 0.034, p = 0.041, and p = 0.008, respectively). Surprisingly, in men with the Berber-specific uniparental markers, the African haplotype was absent, while the prevalence of the Neanderthal haplotype was similar to that in Europeans. The protective rs10774671-G allele of OAS1 was found only in the Neanderthal haplotype in Berbers, the indigenous people of North Africa, suggesting that this region may have served as a stepping-stone for the passage of hominids to other continents.},
}

Adult
Aged
Female
Humans
Male
Middle Aged
*2',5'-Oligoadenylate Synthetase/genetics
Africa, Northern
Alleles
*COVID-19/genetics/virology/epidemiology
Gene Frequency
Genetic Predisposition to Disease
Genotype
Haplotypes
North African People
*Polymorphism, Single Nucleotide
Prevalence

@article {pmid38638564,
year = {2024},
author = {Chen, S and Tang, D and Deng, L and Xu, S},
title = {Asian-European differentiation of schizophrenia-associated genes driven by admixture and natural selection.},
journal = {iScience},
volume = {27},
number = {5},
pages = {109560},
pmid = {38638564},
issn = {2589-0042},
abstract = {The European-centered genome-wide association studies of schizophrenia (SCZ) may not be well applied to non-European populations. We analyzed 1,592 reported SCZ-associated genes using the public genome data and found an overall higher Asian-European differentiation on the SCZ-associated variants than at the genome-wide level. Notable examples included 15 missense variants, a regulatory variant SLC5A10-rs1624825, and a damaging variant TSPAN18-rs1001292. Independent local adaptations in recent 25,000 years, after the Asian-European divergence, could have contributed to such genetic differentiation, as were identified at a missense mutation LTN1-rs57646126-A in Asians, and a non-risk allele ZSWIM6-rs72761442-G in Europeans. Altai-Neanderthal-derived alleles may have opposite effects on SCZ susceptibility between ancestries. Furthermore, adaptive introgression was detected on the non-risk haplotype at 1q21.2 in Europeans, while in Asians it was observed on the SCZ risk haplotype at 3p21.31 which is also potentially ultra-violet protective. This study emphasizes the importance of including more representative Asian samples in future SCZ studies.},
}

@article {pmid38612593,
year = {2024},
author = {Ferreira, RC and Rodrigues, CR and Broach, JR and Briones, MRS},
title = {Convergent Mutations and Single Nucleotide Variants in Mitochondrial Genomes of Modern Humans and Neanderthals.},
journal = {International journal of molecular sciences},
volume = {25},
number = {7},
pages = {},
pmid = {38612593},
issn = {1422-0067},
support = {20/08943-5//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 311154/2021-2//National Council for Scientific and Technological Development/ ; },
mesh = {Humans ; Animals ; *Neanderthals/genetics ; *Genome, Mitochondrial ; Mutation ; *Alzheimer Disease ; Nucleotides ; },
abstract = {The genetic contributions of Neanderthals to the modern human genome have been evidenced by the comparison of present-day human genomes with paleogenomes. Neanderthal signatures in extant human genomes are attributed to intercrosses between Neanderthals and archaic anatomically modern humans (AMHs). Although Neanderthal signatures are well documented in the nuclear genome, it has been proposed that there is no contribution of Neanderthal mitochondrial DNA to contemporary human genomes. Here we show that modern human mitochondrial genomes contain 66 potential Neanderthal signatures, or Neanderthal single nucleotide variants (N-SNVs), of which 36 lie in coding regions and 7 result in nonsynonymous changes. Seven N-SNVs are associated with traits such as cycling vomiting syndrome, Alzheimer's disease and Parkinson's disease, and two N-SNVs are associated with intelligence quotient. Based on recombination tests, principal component analysis (PCA) and the complete absence of these N-SNVs in 41 archaic AMH mitogenomes, we conclude that convergent evolution, and not recombination, explains the presence of N-SNVs in present-day human mitogenomes.},
}

Humans
Animals
*Neanderthals/genetics
*Genome, Mitochondrial
Mutation
*Alzheimer Disease
Nucleotides

@article {pmid38565571,
year = {2024},
author = {Yaworsky, PM and Nielsen, ES and Nielsen, TK},
title = {The Neanderthal niche space of Western Eurasia 145 ka to 30 ka ago.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {7788},
pmid = {38565571},
issn = {2045-2322},
support = {9062-00027B//Danmarks Frie Forskningsfond/ ; },
mesh = {Animals ; *Neanderthals ; Fossils ; },
abstract = {Neanderthals occupied Western Eurasia between 350 ka and 40 ka ago, during the climatically volatile Pleistocene. A key issue is to what extent Neanderthal populations expanded into areas of Western Eurasia and what conditions facilitated such range expansions. The range extent of Neanderthals is generally based on the distribution of Neanderthal material, but the land-altering nature of glacial periods has erased much of the already sparse material evidence of Neanderthals, particularly in the northern latitudes. To overcome this obstacle species distribution models can estimate past distributions of Neanderthals, however, most implementations are generally constrained spatially and temporally and may be artificially truncating the Neanderthal niche space. Using dated contexts from Neanderthal sites from across Western Eurasia, millennial-scale paleoclimate reconstructions, and a spatiotemporal species distribution model, we infer the fundamental climatic niche space of Neanderthals and estimate the extent of Neanderthal occupation. We find that (a.) despite the long timeframe, Neanderthals occupy a relatively narrow fundamental climatic niche space, (b.) the estimated projected potential Neanderthal niche space suggests a larger geographic range than the material record suggests, and (c.) that there was a general decline in the size of the projected potential Neanderthal niche from 145 ka ago onward, possibly contributing to their extinction.},
}

Animals
*Neanderthals
Fossils

@article {pmid38558123,
year = {2024},
author = {Aneli, S and Ceccatelli Berti, C and Gilea, AI and Birolo, G and Mutti, G and Pavesi, A and Baruffini, E and Goffrini, P and Capelli, C},
title = {Functional characterization of archaic-specific variants in mitonuclear genes: insights from comparative analysis in S. cerevisiae.},
journal = {Human molecular genetics},
volume = {33},
number = {13},
pages = {1152-1163},
doi = {10.1093/hmg/ddae057},
pmid = {38558123},
issn = {1460-2083},
support = {//Departments of Excellence/ ; //Italian Ministry for University and Research (MIUR, 2018-2022 and MUR, 2023-2027)/ ; //Programma Nazionale della Ricerca PNR 2021-2027 e PON "Ricerca e Innovazione" 2014-2020-progetti di ricerca su tematiche "Innovazione" e "Green"/ ; RF-2016-02361241//Italian Ministry of Health/ ; //University of Parma/ ; GGP19287A//Italian Telethon Foundation/ ; },
mesh = {Humans ; *Saccharomyces cerevisiae/genetics ; *Neanderthals/genetics ; Animals ; Genetic Variation ; Mitochondria/genetics/metabolism ; Alleles ; Genetic Introgression ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; },
abstract = {Neanderthal and Denisovan hybridisation with modern humans has generated a non-random genomic distribution of introgressed regions, the result of drift and selection dynamics. Cross-species genomic incompatibility and more efficient removal of slightly deleterious archaic variants have been proposed as selection-based processes involved in the post-hybridisation purge of archaic introgressed regions. Both scenarios require the presence of functionally different alleles across Homo species onto which selection operated differently according to which populations hosted them, but only a few of these variants have been pinpointed so far. In order to identify functionally divergent archaic variants removed in humans, we focused on mitonuclear genes, which are underrepresented in the genomic landscape of archaic humans. We searched for non-synonymous, fixed, archaic-derived variants present in mitonuclear genes, rare or absent in human populations. We then compared the functional impact of archaic and human variants in the model organism Saccharomyces cerevisiae. Notably, a variant within the mitochondrial tyrosyl-tRNA synthetase 2 (YARS2) gene exhibited a significant decrease in respiratory activity and a substantial reduction of Cox2 levels, a proxy for mitochondrial protein biosynthesis, coupled with the accumulation of the YARS2 protein precursor and a lower amount of mature enzyme. Our work suggests that this variant is associated with mitochondrial functionality impairment, thus contributing to the purging of archaic introgression in YARS2. While different molecular mechanisms may have impacted other mitonuclear genes, our approach can be extended to the functional screening of mitonuclear genetic variants present across species and populations.},
}

Humans
*Saccharomyces cerevisiae/genetics
*Neanderthals/genetics
Animals
Genetic Variation
Mitochondria/genetics/metabolism
Alleles
Genetic Introgression
Saccharomyces cerevisiae Proteins/genetics/metabolism

@article {pmid38552260,
year = {2024},
author = {Rmoutilová, R and Brůžek, J and Gómez-Olivencia, A and Madelaine, S and Couture-Veschambre, C and Holliday, T and Maureille, B},
title = {Sex estimation of the adult Neandertal Regourdou 1 (Montignac, France): Implications for sexing human fossil remains.},
journal = {Journal of human evolution},
volume = {189},
number = {},
pages = {103470},
doi = {10.1016/j.jhevol.2023.103470},
pmid = {38552260},
issn = {1095-8606},
mesh = {Animals ; Humans ; Male ; *Neanderthals/anatomy & histology ; Fossils ; Genomics ; Paleontology ; *Hominidae ; France ; },
abstract = {Sex is a biological trait fundamental to the study of hominin fossils. Among the many questions that can be addressed are those related to taxonomy, biological variability, sexual dimorphism, paleoobstetrics, funerary selection, and paleodemography. While new methodologies such as paleogenomics or paleoproteomics can be used to determine sex, they have not been systematically applied to Pleistocene human remains due to their destructive nature. Therefore, we estimated sex from the coxal bone of the newly discovered pelvic remains of the Regourdou 1 Neandertal (Southwest France, MIS 5) based on morphological and metric data employing two methods that have been recently revised and shown to be reliable in multiple studies. Both methods calculate posterior probabilities of the estimate. The right coxal bone of Regourdou 1 was partially reconstructed providing additional traits for sex estimation. These methods were cross validated on 14 sufficiently preserved coxal bones of specimens from the Neandertal lineage. Our results show that the Regourdou 1 individual, whose postcranial skeleton is not robust, is a male, and that previous sex attributions of comparative Neandertal specimens are largely in agreement with those obtained here. Our results encourage additional morphological research of fossil hominins in order to develop a set of methods that are applicable, reliable, and reproducible.},
}

Animals
Humans
Male
*Neanderthals/anatomy & histology
Fossils
Genomics
Paleontology
*Hominidae
France

@article {pmid38489387,
year = {2024},
author = {Groh, JS and Coop, G},
title = {The temporal and genomic scale of selection following hybridization.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {12},
pages = {e2309168121},
pmid = {38489387},
issn = {1091-6490},
support = {R35 GM136290/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Humans ; *Genome/genetics ; Genomics ; Hybridization, Genetic ; Nucleic Acid Hybridization ; Haplotypes ; *Neanderthals/genetics ; Selection, Genetic ; },
abstract = {Genomic evidence supports an important role for selection in shaping patterns of introgression along the genome, but frameworks for understanding the evolutionary dynamics within hybrid populations that underlie these patterns have been lacking. Due to the clock-like effect of recombination in hybrids breaking up parental haplotypes, drift and selection produce predictable patterns of ancestry variation at varying spatial genomic scales through time. Here, we develop methods based on the Discrete Wavelet Transform to study the genomic scale of local ancestry variation and its association with recombination rates and show that these methods capture temporal dynamics of drift and genome-wide selection after hybridization. We apply these methods to published datasets from hybrid populations of swordtail fish (Xiphophorus) and baboons (Papio) and to inferred Neanderthal introgression in modern humans. Across systems, upward of 20% of variation in local ancestry at the broadest genomic scales can be attributed to systematic selection against introgressed alleles, consistent with strong selection acting on early-generation hybrids. Signatures of selection at fine genomic scales suggest selection over longer time scales; however, we suggest that our ability to confidently infer selection at fine scales is likely limited by inherent biases in current methods for estimating local ancestry from contiguous segments of genomic similarity. Wavelet approaches will become widely applicable as genomic data from systems with introgression become increasingly available and can help shed light on generalities of the genomic consequences of interspecific hybridization.},
}

Animals
Humans
*Genome/genetics
Genomics
Hybridization, Genetic
Nucleic Acid Hybridization
Haplotypes
*Neanderthals/genetics
Selection, Genetic

@article {pmid38477186,
year = {2024},
author = {Pablos, A and Arsuaga, JL},
title = {Tarsals from the Sima de los Huesos Middle Pleistocene site (Atapuerca, Burgos, Spain).},
journal = {Anatomical record (Hoboken, N.J. : 2007)},
volume = {307},
number = {7},
pages = {2635-2664},
doi = {10.1002/ar.25425},
pmid = {38477186},
issn = {1932-8494},
support = {PGC2018-093925-B-C33//MCI/AEI/FEDER, UE/ ; PGC2018-093925-B-C31//MCI/AEI/FEDER, UE/ ; PID2021-122355NB-C31//MCIN/AEI/10.13039/501100011033/FEDER, UE/ ; 949330/ERC_/European Research Council/International ; EMERGIA20_00403//Junta de Andalucía, Spain/ ; //Junta de Castilla y León and Fundación Atapuerca/ ; },
mesh = {Animals ; *Fossils/anatomy & histology ; Spain ; *Hominidae/anatomy & histology ; *Biological Evolution ; Tarsal Bones/anatomy & histology ; Neanderthals/anatomy & histology ; Humans ; Male ; Female ; },
abstract = {Here, we provide a complete, updated, and illustrated inventory, as well as a comprehensive study, of the tarsals (rearfoot) recovered from the Middle Pleistocene site of Sima de los Huesos (SH, Atapuerca, Spain) in comparison to other Homo comparative samples, both extant and fossil. The minimum number of individuals (MNI) estimated from the tarsals has been established as 15, which represents 51.7% of the 29 dental individuals identified within the SH sample. Within the SH hominin foot sample, an exclusive combination of primitive or plesiomorphic and derived or autapomorphic traits can be observed when compared with other Homo individuals/populations. Other characters are shared among SH hominins and Neandertals that might represent shared derived or autapomorphic traits for this evolutionary line, and most are likely related to robusticity (e.g., rectangular-like trochlea of the talus, broad calcanei, broad naviculars, and short lateral cuneiforms). Additionally, we observed some exclusive autapomorphic traits in the SH tarsal sample (e.g., narrow head of the talus and short intermediate cuneiforms). A few exclusive traits in SH tarsal remains are even more robust than in Neandertals (e.g., broad lateral malleolar facet in talus, more projected sustentaculum tali, and broad medial cuneiform). These traits could suggest a slightly higher level of gracilization in the tarsal bones of Neandertals compared to the SH sample that is also supported by other anatomical postcranial skeleton elements. Additionally, some paleobiological inferences are made in relation to body size (stature and body mass) and some associations are proposed within the SH sample. In conclusion, the morphology of the SH tarsi confirms an evolutionary relationship of sister groups between this population and Neandertals, probably representing a morphotype similar to the Neandertal ancestors.},
}

Animals
*Fossils/anatomy & histology
Spain
*Hominidae/anatomy & histology
*Biological Evolution
Tarsal Bones/anatomy & histology
Neanderthals/anatomy & histology
Humans
Male
Female

@article {pmid38461589,
year = {2024},
author = {Najafzadeh, A and Hernaiz-García, M and Benazzi, S and Chen, B and Hublin, JJ and Kullmer, O and Pokhojaev, A and Sarig, R and Sorrentino, R and Vazzana, A and Fiorenza, L},
title = {Finite element analysis of Neanderthal and early Homo sapiens maxillary central incisor.},
journal = {Journal of human evolution},
volume = {189},
number = {},
pages = {103512},
doi = {10.1016/j.jhevol.2024.103512},
pmid = {38461589},
issn = {1095-8606},
mesh = {Humans ; Adolescent ; Animals ; *Neanderthals ; Incisor ; Computer Simulation ; Finite Element Analysis ; Crowns ; Stress, Mechanical ; },
abstract = {Neanderthal anterior teeth are very large and have a distinctive morphology characterized by robust 'shovel-shaped' crowns. These features are frequently seen as adaptive responses in dissipating heavy mechanical loads resulting from masticatory and non-masticatory activities. Although the long-standing debate surrounding this hypothesis has played a central role in paleoanthropology, is still unclear if Neanderthal anterior teeth can resist high mechanical loads or not. A novel way to answer this question is to use a multidisciplinary approach that considers together tooth architecture, dental wear and jaw movements. The aim of this study is to functionally reposition the teeth of Le Moustier 1 (a Neanderthal adolescent) and Qafzeh 9 (an early Homo sapiens adolescent) derived from wear facet mapping, occlusal fingerprint analysis and physical dental restoration methods. The restored dental arches are then used to perform finite element analysis on the left central maxillary incisor during edge-to-edge occlusion. The results show stress distribution differences between Le Moustier 1 and Qafzeh 9, with the former displaying higher tensile stress in enamel around the lingual fossa but lower concentration of stress in the lingual aspect of the root surface. These results seem to suggest that the presence of labial convexity, lingual tubercle and of a large root surface in Le Moustier 1 incisor helps in dissipating mechanical stress. The absence of these dental features in Qafzeh 9 is compensated by the presence of a thicker enamel, which helps in reducing the stress in the tooth crown.},
}

Humans
Adolescent
Animals
*Neanderthals
Incisor
Computer Simulation
Finite Element Analysis
Crowns
Stress, Mechanical

@article {pmid38458749,
year = {2024},
author = {Geier, A and Trost, J and Wang, K and Schmid, C and Krawczyk, M and Schiffels, S},
title = {PNPLA3 fatty liver allele was fixed in Neanderthals and segregates neutrally in humans.},
journal = {Gut},
volume = {73},
number = {6},
pages = {1008-1014},
doi = {10.1136/gutjnl-2023-331594},
pmid = {38458749},
issn = {1468-3288},
support = {851511/ERC_/European Research Council/International ; },
mesh = {Animals ; Humans ; *Acyltransferases/genetics ; *Alleles ; DNA, Ancient/analysis ; *Fatty Liver/genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; *Neanderthals/genetics ; *Phospholipases A2, Calcium-Independent/genetics ; },
abstract = {OBJECTIVE: Fat deposition is modulated by environmental factors and genetic predisposition. Genome-wide association studies identified PNPLA3 p.I148M (rs738409) as a common variant that increases risk of developing liver steatosis. When and how this variant evolved in humans has not been studied to date.

DESIGN: Here we analyse ancient DNA to track the history of this allele throughout human history. In total, 6444 published ancient (modern humans, Neanderthal, Denisovan) and 3943 published present day genomes were used for analysis after extracting genotype calls for PNPLA3 p.I148M. To quantify changes through time, logistic and, by grouping individuals according to geography and age, linear regression analyses were performed.

RESULTS: We find that archaic human individuals (Neanderthal, Denisovan) exclusively carried a fixed PNPLA3 risk allele, whereas allele frequencies in modern human populations range from very low in Africa to >50% in Mesoamerica. Over the last 15 000 years, distributions of ancestral and derived alleles roughly match the present day distribution. Logistic regression analyses did not yield signals of natural selection during the last 10 000 years.

CONCLUSION: Archaic human individuals exclusively carried a fixed PNPLA3 allele associated with fatty liver, whereas allele frequencies in modern human populations are variable even in the oldest samples. Our observation might underscore the advantage of fat storage in cold climate and particularly for Neanderthal under ice age conditions. The absent signals of natural selection during modern human history does not support the thrifty gene hypothesis in case of PNPLA3 p.I148M.},
}

Animals
Humans
*Acyltransferases/genetics
*Alleles
DNA, Ancient/analysis
*Fatty Liver/genetics
Gene Frequency
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
*Neanderthals/genetics
*Phospholipases A2, Calcium-Independent/genetics

@article {pmid38454744,
year = {2024},
author = {Pantoja-Pérez, A and Arsuaga, JL},
title = {The Cranium I: Neurocranium.},
journal = {Anatomical record (Hoboken, N.J. : 2007)},
volume = {307},
number = {7},
pages = {2278-2324},
doi = {10.1002/ar.25413},
pmid = {38454744},
issn = {1932-8494},
support = {PID2021-122355NB-C31//MCIN/AEI/10.13039/501100011033 and "ERDF A way of making Europe"/ ; PGC2018-093925-B-C31//MCIN/AEI/10.13039/501100011033 and "ERDF A way of making Europe"/ ; 949330//European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program/ ; //CaixaBank-Fundación Atapuerca/ ; },
mesh = {Animals ; *Skull/anatomy & histology ; *Neanderthals/anatomy & histology ; Male ; Female ; *Fossils ; Humans ; *Biological Evolution ; },
abstract = {The Sima de los Huesos (SH) site has provided a significant collection of hominin remains, including numerous cranial fragments, which have contributed to our understanding of the MP human population. The taxonomic classification of the SH hominins remains a topic of debate, with some studies suggesting a close relationship to Neandertals based on nuclear DNA analysis. The cranial morphology of the SH specimens exhibits a mix of Neandertal-like features and primitive traits observed in earlier Homo populations, providing insights into the evolutionary pattern of the Neanderthal lineage. This study focuses on the neurocranial traits of the SH population and describes three previously undescribed cranial individuals. The SH cranial collection now comprises 20 nearly complete crania, representing approximately two-thirds of the estimated population size. The analysis of the SH population reveals variations in robustness, frontal torus development, sagittal keeling, and occipital torus morphology, which may be related to sexual dimorphism and ontogenetic factors. The suprainiac region exhibits notable ontogenetic changes, while suture obliteration patterns do not strictly correlate with dental age. Metric measurements, particularly cranial breadths, highlight significant intrapopulation variation within the SH sample. Compared with other Middle Pleistocene (MP) hominins, the SH cranial vault displays archaic characteristics but differs from Homo erectus and Neandertals. The SH individuals have relatively short and tall cranial vaults, distinguishing them from other MP fossils. These findings contribute to our understanding of the MP human populations and their evolutionary trajectories.},
}

Animals
*Skull/anatomy & histology
*Neanderthals/anatomy & histology
Male
Female
*Fossils
Humans
*Biological Evolution

@article {pmid38450997,
year = {2024},
author = {Gómez-Olivencia, A and Arsuaga, JL},
title = {The Sima de los Huesos thorax and lumbar spine: Selected traits and state-of-the-art.},
journal = {Anatomical record (Hoboken, N.J. : 2007)},
volume = {307},
number = {7},
pages = {2465-2490},
doi = {10.1002/ar.25414},
pmid = {38450997},
issn = {1932-8494},
support = {PGC2018-093925-B-C33//Ministerio de Ciencia, Innovación y Universidades/ ; PID2021-122355NB-C31//Ministerio de Ciencia, Innovación y Universidades/ ; RYC-2017-22558//Ramón y Cajal fellowship/ ; //Fundación Atapuerca/ ; //Junta de Castilla y León/ ; },
mesh = {*Lumbar Vertebrae/anatomy & histology ; Animals ; *Fossils/anatomy & histology ; Humans ; *Thoracic Vertebrae/anatomy & histology ; *Neanderthals/anatomy & histology ; *Biological Evolution ; *Thorax/anatomy & histology ; Ribs/anatomy & histology ; Hominidae/anatomy & histology ; },
abstract = {Information on the evolution of the thorax and lumbar spine in the genus Homo is hampered by a limited fossil record due to the inherent fragility of vertebrae and ribs. Neandertals show significant metric and morphological differences in these two anatomical regions, when compared to Homo sapiens. Thus, the important fossil record from the Middle Pleistocene site of Sima de los Huesos (SH) not only offers important information on the evolution of these anatomical regions within the Neandertal lineage but also provides important clues to understand the evolution of these regions at the genus level. We present the current knowledge of the costal skeleton, and the thoracic and lumbar spine anatomy of the hominins found in Sima de los Huesos compared to that of Neandertals and modern humans. The current SH fossil record comprises 738 vertebral specimens representing a minimum of 70 cervical, 95 thoracic and 47 lumbar vertebrae, 652 rib fragments representing a minimum of 118 ribs, and 26 sternal fragments representing 4 sterna. The SH hominins exhibit a morphological pattern in their thorax and lumbar spine more similar to that of Neandertals than to that of H. sapiens, which is consistent with the phylogenetic position of these hominins. However, there are some differences between the SH hominins and Neandertals in these anatomical regions, primarily in the orientation of the lumbar transverse processes and in the robusticity of the second ribs. The presence of some but not all of the suite of Neandertal-derived features is consistent with the pattern found in the cranium and other postcranial regions of this population.},
}

*Lumbar Vertebrae/anatomy & histology
Animals
*Fossils/anatomy & histology
Humans
*Thoracic Vertebrae/anatomy & histology
*Neanderthals/anatomy & histology
*Biological Evolution
*Thorax/anatomy & histology
Ribs/anatomy & histology
Hominidae/anatomy & histology

@article {pmid38420653,
year = {2024},
author = {Hernaiz-García, M and Zanolli, C and Martín-Francés, L and Mazurier, A and Benazzi, S and Sarig, R and Fu, J and Kullmer, O and Fiorenza, L},
title = {Masticatory habits of the adult Neanderthal individual BD 1 from La Chaise-de-Vouthon (France).},
journal = {American journal of biological anthropology},
volume = {184},
number = {1},
pages = {e24926},
doi = {10.1002/ajpa.24926},
pmid = {38420653},
issn = {2692-7691},
support = {//Biomedicine Discovery Scholarship from Monash University/ ; DP190100465//Australian Research Council/ ; },
mesh = {Adult ; Humans ; Animals ; *Neanderthals ; *Tooth ; *Tooth Wear ; France ; Habits ; },
abstract = {OBJECTIVES: The analysis of dental wear provides a useful approach for dietary and cultural habit reconstructions of past human populations. The analysis of macrowear patterns can also be used to better understand the individual chewing behavior and to investigate the biomechanical responses during different biting scenarios. The aim of this study is to evaluate the diet and chewing performance of the adult Neanderthal Bourgeois-Delaunay 1 (BD 1) and to investigate the relationship between wear and cementum deposition under mechanical demands.

MATERIALS AND METHODS: The macrowear pattern of BD 1 was analyzed using the occlusal fingerprint analysis method. We propose a new method for the bilateral measurement of the cementum volume along both buccal and lingual sides of the molar root.

RESULTS: BD 1's anterior dentition is more affected by wear compared to the posterior one. The macrowear pattern suggest a normal chewing behavior and a mixed-diet coming from temperate environments. The teeth on the left side of the mandible display greater levels of wear, as well as the buccal side of the molar crowns. The cementum analysis shows higher buccal volume along the molar roots.

DISCUSSION: BD1 could have been preferably chewing on the left side of the mandible. The exploitation of various food resources suggested by the macrowear analysis is compatible with the environmental reconstructions. Finally, the greater wear on the buccal side of the molar occlusal surface and the greater volume of cementum in that side of the molar roots offers a preliminary understanding about the potential correlation between dental wear and cementum deposition.},
}

Adult
Humans
Animals
*Neanderthals
*Tooth
*Tooth Wear
France
Habits

@article {pmid38405782,
year = {2024},
author = {Kerdoncuff, E and Skov, L and Patterson, N and Zhao, W and Lueng, YY and Schellenberg, GD and Smith, JA and Dey, S and Ganna, A and Dey, AB and Kardia, SLR and Lee, J and Moorjani, P},
title = {50,000 years of Evolutionary History of India: Insights from ~2,700 Whole Genome Sequences.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {38405782},
issn = {2692-8205},
support = {R01 AG051125/AG/NIA NIH HHS/United States ; R35 GM142978/GM/NIGMS NIH HHS/United States ; RF1 AG055273/AG/NIA NIH HHS/United States ; },
abstract = {India has been underrepresented in whole genome sequencing studies. We generated 2,762 high coverage genomes from India-including individuals from most geographic regions, speakers of all major languages, and tribal and caste groups-providing a comprehensive survey of genetic variation in India. With these data, we reconstruct the evolutionary history of India through space and time at fine scales. We show that most Indians derive ancestry from three ancestral groups related to ancient Iranian farmers, Eurasian Steppe pastoralists and South Asian hunter-gatherers. We uncover a common source of Iranian-related ancestry from early Neolithic cultures of Central Asia into the ancestors of Ancestral South Indians (ASI), Ancestral North Indians (ANI), Austro-asiatic-related and East Asian-related groups in India. Following these admixtures, India experienced a major demographic shift towards endogamy, resulting in extensive homozygosity and identity-by-descent sharing among individuals. At deep time scales, Indians derive around 1-2% of their ancestry from gene flow from archaic hominins, Neanderthals and Denisovans. By assembling the surviving fragments of archaic ancestry in modern Indians, we recover ~1.5 Gb (or 50%) of the introgressing Neanderthal and ~0.6 Gb (or 20%) of the introgressing Denisovan genomes, more than any other previous archaic ancestry study. Moreover, Indians have the largest variation in Neanderthal ancestry, as well as the highest amount of population-specific Neanderthal segments among worldwide groups. Finally, we demonstrate that most of the genetic variation in Indians stems from a single major migration out of Africa that occurred around 50,000 years ago, with minimal contribution from earlier migration waves. Together, these analyses provide a detailed view of the population history of India and underscore the value of expanding genomic surveys to diverse groups outside Europe.},
}

@article {pmid38380556,
year = {2024},
author = {Pablos, A and Arsuaga, JL},
title = {Metatarsals and foot phalanges from the Sima de los Huesos Middle Pleistocene site (Atapuerca, Burgos, Spain).},
journal = {Anatomical record (Hoboken, N.J. : 2007)},
volume = {307},
number = {7},
pages = {2665-2707},
doi = {10.1002/ar.25412},
pmid = {38380556},
issn = {1932-8494},
support = {PGC2018-093925-B-C33//Ministerio de Ciencia e Innovación/ ; PGC2018-093925-B-C31//Ministerio de Ciencia e Innovación/ ; PID2021-122355NB-C31//MCIN/ ; 949330//H2020 European Research Council/ ; EMERGIA20_00403//EMERGIA/ ; //Junta de Castilla y León/ ; },
mesh = {Animals ; *Fossils/anatomy & histology ; Spain ; *Metatarsal Bones/anatomy & histology ; Humans ; *Hominidae/anatomy & histology/physiology ; Biological Evolution ; Neanderthals/anatomy & histology ; Toe Phalanges/anatomy & histology ; },
abstract = {This study provides a complete, updated and illustrated inventory, as well as a comprehensive study, of the metatarsals and foot phalanges (forefoot) recovered from the Middle Pleistocene site of Sima de los Huesos (SH, Atapuerca, Spain) in comparison to other Homo comparative samples, both extant and fossils. This current updated review has established a minimum number of individuals (MNI) of 17, which represent 58.6% of the 29 dental individuals identified within the SH sample. An exclusive or autoapomorphic combination of traits can be recognized within the SH hominin foot sample. A few traits appear primitive or plesiomorphic when compared with earlier Homo individuals and other recent modern humans. There are other metrical and morphological traits that SH hominins and Neandertals have in common that sometimes represent shared derived traits in this evolutionary line, most of which are probably related to robusticity. Furthermore, some exclusive autoapomorphic traits are observed in the SH sample: a very broad first metatarsal, long and broad hallucal proximal foot phalanges and possibly extremely robust lateral distal foot phalanges compared to those of Neandertals and modern humans. In these last traits, the SH metatarsals and pedal phalanges are even more robust than in Neandertals. They are herein named as "hyper-Neandertal" traits, which could suggest a slight gracilization process in this evolutionary line, at least in the hallux toe. Finally, some paleobiological inferences are made in relation to body size (stature and body mass) and some associations are proposed within the SH sample.},
}

Animals
*Fossils/anatomy & histology
Spain
*Metatarsal Bones/anatomy & histology
Humans
*Hominidae/anatomy & histology/physiology
Biological Evolution
Neanderthals/anatomy & histology
Toe Phalanges/anatomy & histology

@article {pmid38379413,
year = {2024},
author = {Cerrito, P and Nava, A and Radovčić, D and Borić, D and Cerrito, L and Basdeo, T and Ruggiero, G and Frayer, DW and Kao, AP and Bondioli, L and Mancini, L and Bromage, TG},
title = {Correction: 'Dental cementum virtual histology of Neanderthal teeth from Krapina (Croatia, 130-120 kyr): an informed estimate of age, sex and adult stressors' (2022), by Cerrito et al.},
journal = {Journal of the Royal Society, Interface},
volume = {21},
number = {211},
pages = {20240069},
doi = {10.1098/rsif.2024.0069},
pmid = {38379413},
issn = {1742-5662},
}

@article {pmid38377343,
year = {2024},
author = {Liu, S and Luo, H and Zhang, P and Li, Y and Hao, D and Zhang, S and Song, T and Xu, T and He, S},
title = {Adaptive Selection of Cis-regulatory Elements in the Han Chinese.},
journal = {Molecular biology and evolution},
volume = {41},
number = {3},
pages = {},
pmid = {38377343},
issn = {1537-1719},
support = {XDB38040300//Chinese Academy of Sciences/ ; 2021YFF0703701//National Key R&D Program of China/ ; 91940306//National Natural Science Foundation of China/ ; 2019FY100102//MOST, China/ ; 2022M713311//China Postdoctoral Science Foundation/ ; //National Genomics Data Center, China/ ; },
mesh = {Humans ; Animals ; *Diabetes Mellitus, Type 2/genetics ; Selection, Genetic ; Regulatory Sequences, Nucleic Acid ; Promoter Regions, Genetic ; *Neanderthals/genetics ; China ; Enhancer Elements, Genetic ; },
abstract = {Cis-regulatory elements have an important role in human adaptation to the living environment. However, the lag in population genomic cohort studies and epigenomic studies, hinders the research in the adaptive analysis of cis-regulatory elements in human populations. In this study, we collected 4,013 unrelated individuals and performed a comprehensive analysis of adaptive selection of genome-wide cis-regulatory elements in the Han Chinese. In total, 12.34% of genomic regions are under the influence of adaptive selection, where 1.00% of enhancers and 2.06% of promoters are under positive selection, and 0.06% of enhancers and 0.02% of promoters are under balancing selection. Gene ontology enrichment analysis of these cis-regulatory elements under adaptive selection reveals that many positive selections in the Han Chinese occur in pathways involved in cell-cell adhesion processes, and many balancing selections are related to immune processes. Two classes of adaptive cis-regulatory elements related to cell adhesion were in-depth analyzed, one is the adaptive enhancers derived from neanderthal introgression, leads to lower hyaluronidase level in skin, and brings better performance on UV-radiation resistance to the Han Chinese. Another one is the cis-regulatory elements regulating wound healing, and the results suggest the positive selection inhibits coagulation and promotes angiogenesis and wound healing in the Han Chinese. Finally, we found that many pathogenic alleles, such as risky alleles of type 2 diabetes or schizophrenia, remain in the population due to the hitchhiking effect of positive selections. Our findings will help deepen our understanding of the adaptive evolution of genome regulation in the Han Chinese.},
}

Humans
Animals
*Diabetes Mellitus, Type 2/genetics
Selection, Genetic
Regulatory Sequences, Nucleic Acid
Promoter Regions, Genetic
*Neanderthals/genetics
China
Enhancer Elements, Genetic

@article {pmid38367960,
year = {2024},
author = {Voinescu, CD and Mozere, M and Genovese, G and Downie, ML and Gupta, S and Gale, DP and Bockenhauer, D and Kleta, R and Arcos-Burgos, M and Stanescu, HC},
title = {A Neanderthal haplotype introgressed into the human genome confers protection against membranous nephropathy.},
journal = {Kidney international},
volume = {105},
number = {4},
pages = {791-798},
doi = {10.1016/j.kint.2024.01.017},
pmid = {38367960},
issn = {1523-1755},
mesh = {Humans ; Animals ; *Neanderthals/genetics ; Haplotypes ; *Glomerulonephritis, Membranous/genetics ; Genome, Human ; Genome-Wide Association Study ; Receptors, Phospholipase A2/genetics ; },
abstract = {Class 2 HLA and PLA2R1 alleles are exceptionally strong genetic risk factors for membranous nephropathy (MN), leading, through an unknown mechanism, to a targeted autoimmune response. Introgressed archaic haplotypes (introduced from an archaic human genome into the modern human genome) might influence phenotypes through gene dysregulation. Here, we investigated the genomic region surrounding the PLA2R1 gene. We reconstructed the phylogeny of Neanderthal and modern haplotypes in this region and calculated the probability of the observed clustering being the result of introgression or common descent. We imputed variants for the participants in our previous genome-wide association study and we compared the distribution of Neanderthal variants between MN cases and controls. The region associated with the lead MN risk locus in the PLA2R1 gene was confirmed and showed that, within a 507 kb region enriched in introgressed sequence, a stringently defined 105 kb haplotype, intersecting the coding regions for PLA2R1 and ITGB6, is inherited from Neanderthals. Thus, introgressed Neanderthal haplotypes overlapping PLA2R1 are differentially represented in MN cases and controls, with enrichment In controls suggesting a protective effect.},
}

Humans
Animals
*Neanderthals/genetics
Haplotypes
*Glomerulonephritis, Membranous/genetics
Genome, Human
Genome-Wide Association Study
Receptors, Phospholipase A2/genetics

@article {pmid38345759,
year = {2024},
author = {Yaghmouri, M and Izadi, P},
title = {Role of the Neanderthal Genome in Genetic Susceptibility to COVID-19: 3p21.31 Locus in the Spotlight.},
journal = {Biochemical genetics},
volume = {62},
number = {6},
pages = {4239-4263},
pmid = {38345759},
issn = {1573-4927},
mesh = {*Neanderthals/genetics ; Animals ; Humans ; *COVID-19/genetics ; *Genetic Predisposition to Disease ; *SARS-CoV-2 ; *Chromosomes, Human, Pair 3/genetics ; Genome-Wide Association Study ; },
abstract = {Since the outbreak of COVID-19, genome-wide association studies have tried to discover the role of genetic predisposition in the clinical variability of this viral infection. The findings of various investigations have led to several loci for COVID-19 genetic susceptibility. Among candidate regions, the 3p21.31 locus has been in the spotlight among scientists, as it can increase the risk of severe COVID-19 by almost two fold. In addition to its substantial association with COVID-19 severity, this locus is related to some common diseases, such as diabetes, malignancies, and coronary artery disease. This locus also harbors evolutionary traces of Neanderthal genomes, which is believed to be the underlying reason for its association with COVID-19 severity. Additionally, the inheritance of this locus from Neanderthals seems to be under positive selection. This review aims to summarize a collection of evidence on the 3p21.31 locus and its impact on COVID-19 outcomes by focusing on the risk variants originated from the Neanderthal genome. Moreover, we discuss candidate genes at this locus and the possible mechanisms by which they influence the progression of COVID-19 symptoms. Better insights into human genetic susceptibility to newly emerging diseases such as COVID-19 and its evolutionary origin can provide fundamentals for risk assessment of different populations as well as the development of personalized prevention and treatments based on genomic medicine.},
}

*Neanderthals/genetics
Animals
Humans
*COVID-19/genetics
*Genetic Predisposition to Disease
*SARS-CoV-2
*Chromosomes, Human, Pair 3/genetics
Genome-Wide Association Study

@article {pmid38293167,
year = {2024},
author = {Janivara, R and Hazra, U and Pfennig, A and Harlemon, M and Kim, MS and Eaaswarkhanth, M and Chen, WC and Ogunbiyi, A and Kachambwa, P and Petersen, LN and Jalloh, M and Mensah, JE and Adjei, AA and Adusei, B and Joffe, M and Gueye, SM and Aisuodionoe-Shadrach, OI and Fernandez, PW and Rohan, TE and Andrews, C and Rebbeck, TR and Adebiyi, AO and Agalliu, I and Lachance, J},
title = {Uncovering the genetic architecture and evolutionary roots of androgenetic alopecia in African men.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {38293167},
issn = {2692-8205},
support = {R35 GM133727/GM/NIGMS NIH HHS/United States ; U01 CA184374/CA/NCI NIH HHS/United States ; U01 CA257328/CA/NCI NIH HHS/United States ; },
abstract = {Androgenetic alopecia is a highly heritable trait. However, much of our understanding about the genetics of male pattern baldness comes from individuals of European descent. Here, we examined a novel dataset comprising 2,136 men from Ghana, Nigeria, Senegal, and South Africa that were genotyped using a custom array. We first tested how genetic predictions of baldness generalize from Europe to Africa, finding that polygenic scores from European GWAS yielded AUC statistics that ranged from 0.513 to 0.546, indicating that genetic predictions of baldness in African populations performed notably worse than in European populations. Subsequently, we conducted the first African GWAS of androgenetic alopecia, focusing on self-reported baldness patterns at age 45. After correcting for present age, population structure, and study site, we identified 266 moderately significant associations, 51 of which were independent (p-value < 10[-5], r[2] < 0.2). Most baldness associations were autosomal, and the X chromosomes does not appear to have a large impact on baldness in African men. Finally, we examined the evolutionary causes of continental differences in genetic architecture. Although Neanderthal alleles have previously been associated with skin and hair phenotypes, we did not find evidence that European-ascertained baldness hits were enriched for signatures of ancient introgression. Most loci that are associated with androgenetic alopecia are evolving neutrally. However, multiple baldness-associated SNPs near the EDA2R and AR genes have large allele frequency differences between continents. Collectively, our findings illustrate how evolutionary history contributes to the limited portability of genetic predictions across ancestries.},
}

@article {pmid38269094,
year = {2024},
author = {Jambrina-Enríquez, M and Mallol, C and Herrera Herrera, AV and Gonzalez-Urquijo, J and Lazuen, T},
title = {Microstratigraphic, lipid biomarker and stable isotope study of a middle Palaeolithic combustion feature from Axlor, Spain.},
journal = {iScience},
volume = {27},
number = {1},
pages = {108755},
pmid = {38269094},
issn = {2589-0042},
abstract = {Archaeological research has increasingly focused on studying combustion features as valuable sources of information regarding past technological and cultural aspects. The use of microstratigraphic and biomolecular techniques enables the identification of combustion residues and substrate components, and infer about past fire-related activities and the environments. Our study conducted on a combustion feature (Level N, ∼100 Ka) at the Axlor cave, a Middle Paleolithic site in northern Iberia, exemplifies the interdisciplinary approach to combustion features. Micromorphological features revealed depositional activities associated with occupations such as hearth rake-out and trampling. Through molecular (n-alkanes, n-alcohols, and n-fatty acids) and isotopic analysis (δ[13]C16:0 and δ[13]C18:0), we infer the good preservation of organic matter, the contributions of non-ruminant fats, and the dead-wood gathering strategies by Neanderthal groups. By combining microstratigraphic and biomolecular approaches, our study significantly contributes to the advancement of our current understanding of Neanderthal pyrotechnology.},
}

@article {pmid38262226,
year = {2024},
author = {Bailey, SE and Davies, TW and Imbrasas, MD and Lazuen, T and Hublin, JJ and González-Urquijo, J},
title = {New Neanderthal remains from Axlor cave (Dima, Biscay, northern Iberian Peninsula).},
journal = {Journal of human evolution},
volume = {187},
number = {},
pages = {103483},
doi = {10.1016/j.jhevol.2023.103483},
pmid = {38262226},
issn = {1095-8606},
mesh = {Animals ; *Neanderthals ; Europe ; Fossils ; Caves ; Archaeology ; },
}

Animals
*Neanderthals
Europe
Fossils
Caves
Archaeology

@article {pmid38213708,
year = {2023},
author = {Borodko, DD and Zhenilo, SV and Sharko, FS},
title = {Search for differentially methylated regions in ancient and modern genomes.},
journal = {Vavilovskii zhurnal genetiki i selektsii},
volume = {27},
number = {7},
pages = {820-828},
doi = {10.18699/VJGB-23-95},
pmid = {38213708},
issn = {2500-0462},
abstract = {Currently, active research is focused on investigating the mechanisms that regulate the development of various pathologies and their evolutionary dynamics. Epigenetic mechanisms, such as DNA methylation, play a significant role in evolutionary processes, as their changes have a faster impact on the phenotype compared to mutagenesis. In this study, we attempted to develop an algorithm for identifying differentially methylated regions associated with metabolic syndrome, which have undergone methylation changes in humans during the transition from a hunter-gatherer to a sedentary lifestyle. The application of existing whole-genome bisulfite sequencing methods is limited for ancient samples due to their low quality and fragmentation, and the approach to obtaining DNA methylation profiles differs significantly between ancient hunter-gatherer samples and modern tissues. In this study, we validated DamMet, an algorithm for reconstructing ancient methylomes. Application of DamMet to Neanderthal and Denisovan genomes showed a moderate level of correlation with previously published methylation profiles and demonstrated an underestimation of methylation levels in the reconstructed profiles by an average of 15-20 %. Additionally, we developed a new Python-based algorithm that allows for the comparison of methylomes in ancient and modern samples, despite the absence of methylation profiles in modern bone tissue within the context of obesity. This analysis involves a two-step data processing approach, where the first step involves the identification and filtration of tissue-specific methylation regions, and the second step focuses on the direct search for differentially methylated regions in specific areas associated with the researcher's target condition. By applying this algorithm to test data, we identified 38 differentially methylated regions associated with obesity, the majority of which were located in promoter regions. The pipeline demonstrated sufficient efficiency in detecting these regions. These results confirm the feasibility of reconstructing DNA methylation profiles in ancient samples and comparing them with modern methylomes. Furthermore, possibilities for further methodological development and the implementation of a new step for studying differentially methylated positions associated with evolutionary processes are discussed.},
}

@article {pmid38166646,
year = {2024},
author = {Levinstein Hallak, K and Rosset, S},
title = {Dating ancient splits in phylogenetic trees, with application to the human-Neanderthal split.},
journal = {BMC genomic data},
volume = {25},
number = {1},
pages = {4},
pmid = {38166646},
issn = {2730-6844},
support = {2180/20//Israeli Science Foundation grant/ ; },
mesh = {Animals ; Humans ; *Neanderthals/genetics ; Phylogeny ; Pan troglodytes/genetics ; Bayes Theorem ; *Hominidae/genetics ; DNA, Mitochondrial/genetics ; },
abstract = {BACKGROUND: We tackle the problem of estimating species TMRCAs (Time to Most Recent Common Ancestor), given a genome sequence from each species and a large known phylogenetic tree with a known structure (typically from one of the species). The number of transitions at each site from the first sequence to the other is assumed to be Poisson distributed, and only the parity of the number of transitions is observed. The detailed phylogenetic tree contains information about the transition rates in each site. We use this formulation to develop and analyze multiple estimators of the species' TMRCA. To test our methods, we use mtDNA substitution statistics from the well-established Phylotree as a baseline for data simulation such that the substitution rate per site mimics the real-world observed rates.

RESULTS: We evaluate our methods using simulated data and compare them to the Bayesian optimizing software BEAST2, showing that our proposed estimators are accurate for a wide range of TMRCAs and significantly outperform BEAST2. We then apply the proposed estimators on Neanderthal, Denisovan, and Chimpanzee mtDNA genomes to better estimate their TMRCA with modern humans and find that their TMRCA is substantially later, compared to values cited recently in the literature.

CONCLUSIONS: Our methods utilize the transition statistics from the entire known human mtDNA phylogenetic tree (Phylotree), eliminating the requirement to reconstruct a tree encompassing the specific sequences of interest. Moreover, they demonstrate notable improvement in both running speed and accuracy compared to BEAST2, particularly for earlier TMRCAs like the human-Chimpanzee split. Our results date the human - Neanderthal TMRCA to be [Formula: see text] years ago, considerably later than values cited in other recent studies.},
}

Animals
Humans
*Neanderthals/genetics
Phylogeny
Pan troglodytes/genetics
Bayes Theorem
*Hominidae/genetics
DNA, Mitochondrial/genetics

@article {pmid38113553,
year = {2024},
author = {Palancar, CA and Bastir, M and Rosas, A and Dugailly, PM and Schlager, S and Beyer, B},
title = {Modern human atlas ranges of motion and Neanderthal estimations.},
journal = {Journal of human evolution},
volume = {187},
number = {},
pages = {103482},
doi = {10.1016/j.jhevol.2023.103482},
pmid = {38113553},
issn = {1095-8606},
mesh = {Humans ; Animals ; *Neanderthals ; Cervical Vertebrae ; Range of Motion, Articular ; Rotation ; Biomechanical Phenomena ; },
}

Humans
Animals
*Neanderthals
Cervical Vertebrae
Range of Motion, Articular
Rotation
Biomechanical Phenomena

@article {pmid38110796,
year = {2024},
author = {Zhao, H and Liu, LL and Sun, J and Jin, L and Xie, HB and Li, JB and Xu, H and Wu, DD and Zhuang, XL and Peng, MS and Guo, YJ and Qian, WZ and Otecko, NO and Sun, WJ and Qu, LH and He, J and Chen, ZL and Liu, R and Chen, CS and Zhang, YP},
title = {A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression.},
journal = {Science China. Life sciences},
volume = {67},
number = {4},
pages = {765-777},
pmid = {38110796},
issn = {1869-1889},
mesh = {Humans ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; *Gene Expression Regulation, Neoplastic ; Introns ; },
abstract = {Human-specific insertions play important roles in human phenotypes and diseases. Here we reported a 446-bp insertion (Insert-446) in intron 11 of the TBC1D8B gene, located on chromosome X, and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5. Interestingly, Insert-446 was present in the human Neanderthal and Denisovans genomes, and was fixed in humans after human-chimpanzee divergence. We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques. In addition, over-expression TBC1D8B promoted cell proliferation and migration through "a dual finger" catalytic mechanism (Arg538 and Gln573) in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo. Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells. Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene. These findings provide a significant insight into the effects of human-specific insertions on evolution.},
}

Humans
Cell Line, Tumor
Cell Movement/genetics
Cell Proliferation/genetics
*Gene Expression Regulation, Neoplastic
Introns

@article {pmid38051947,
year = {2023},
author = {Wroblewski, TH and Witt, KE and Lee, SB and Malhi, RS and Peede, D and Huerta-Sánchez, E and Villanea, FA and Claw, KG},
title = {Pharmacogenetic Variation in Neanderthals and Denisovans and Implications for Human Health and Response to Medications.},
journal = {Genome biology and evolution},
volume = {15},
number = {12},
pages = {},
pmid = {38051947},
issn = {1759-6653},
support = {1R35GM128946-01/NH/NIH HHS/United States ; R35 HG011319/HG/NHGRI NIH HHS/United States ; R35 GM128946/GM/NIGMS NIH HHS/United States ; R35HG011319/HG/NHGRI NIH HHS/United States ; T32 GM128596/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Humans ; *Neanderthals/genetics ; Pharmacogenetics ; Genome, Human ; *Hominidae/genetics ; Biological Evolution ; },
abstract = {Modern humans carry both Neanderthal and Denisovan (archaic) genome elements that are part of the human gene pool and affect the life and health of living individuals. The impact of archaic DNA may be particularly evident in pharmacogenes-genes responsible for the processing of exogenous substances such as food, pollutants, and medications-as these can relate to changing environmental effects, and beneficial variants may have been retained as modern humans encountered new environments. However, the health implications and contribution of archaic ancestry in pharmacogenes of modern humans remain understudied. Here, we explore 11 key cytochrome P450 genes (CYP450) involved in 75% of all drug metabolizing reactions in three Neanderthal and one Denisovan individuals and examine archaic introgression in modern human populations. We infer the metabolizing efficiency of these 11 CYP450 genes in archaic individuals and find important predicted phenotypic differences relative to modern human variants. We identify several single nucleotide variants shared between archaic and modern humans in each gene, including some potentially function-altering mutations in archaic CYP450 genes, which may result in altered metabolism in living people carrying these variants. We also identified several variants in the archaic CYP450 genes that are novel and unique to archaic humans as well as one gene, CYP2B6, that shows evidence for a gene duplication found only in Neanderthals and modern Africans. Finally, we highlight CYP2A6, CYP2C9, and CYP2J2, genes which show evidence for archaic introgression into modern humans and posit evolutionary hypotheses that explain their allele frequencies in modern populations.},
}

Animals
Humans
*Neanderthals/genetics
Pharmacogenetics
Genome, Human
*Hominidae/genetics
Biological Evolution

@article {pmid38048457,
year = {2023},
author = {Gaudzinski-Windheuser, S and Kindler, L and Roebroeks, W},
title = {Widespread evidence for elephant exploitation by Last Interglacial Neanderthals on the North European plain.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {120},
number = {50},
pages = {e2309427120},
pmid = {38048457},
issn = {1091-6490},
support = {K283/2019//IPF | Leibniz-Gemeinschaft (LG)/ ; GA 683/7-1//Deutsche Forschungsgemeinschaft (DFG)/ ; Zielgerade//Gutenberg Forschungskolleg (GRC)/ ; 28-548//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)/ ; },
mesh = {Male ; Animals ; *Elephants ; *Neanderthals ; Mammals ; Germany ; *Tooth ; Fossils ; },
abstract = {Neanderthals hunted and butchered straight-tusked elephants, the largest terrestrial mammals of the Pleistocene, in a lake landscape on the North European plain, 125,000 years ago, as recently shown by a study of the Last Interglacial elephant assemblage from Neumark-Nord (Germany). With evidence for a remarkable focus on adult males and on their extended utilization, the data from this location are thus far without parallel in the archaeological record. Given their relevance for our knowledge of the Neanderthal niche, we investigated whether the Neumark-Nord subsistence practices were more than a local phenomenon, possibly determined by local characteristics. Analyzing elephant remains from two other Last Interglacial archaeological sites on the North European plain, Gröbern and Taubach, we identified in both assemblages similar butchering patterns as at Neumark-Nord, demonstrating that extended elephant exploitation was a widespread Neanderthal practice during the (early part of the) Last Interglacial. The substantial efforts needed to process these animals, weighing up to 13 metric tons, and the large amounts of food generated suggest that Neanderthals either had ways of storing vast amounts of meat and fat and/or temporarily aggregated in larger groups than commonly acknowledged. The data do not allow us to rule out one of the two explanations, and furthermore both factors, short-term larger group sizes as well as some form of food preservation, may have played a role. What the data do show is that exploitation of large straight-tusked elephants was a widespread and recurring phenomenon amongst Last Interglacial Neanderthals on the North European plain.},
}

Male
Animals
*Elephants
*Neanderthals
Mammals
Germany
*Tooth
Fossils

@article {pmid38020913,
year = {2023},
author = {Agata, A and Ohtsuka, S and Noji, R and Gotoh, H and Ono, K and Nomura, T},
title = {A Neanderthal/Denisovan GLI3 variant contributes to anatomical variations in mice.},
journal = {Frontiers in cell and developmental biology},
volume = {11},
number = {},
pages = {1247361},
pmid = {38020913},
issn = {2296-634X},
abstract = {Changes in genomic structures underlie phenotypic diversification in organisms. Amino acid-changing mutations affect pleiotropic functions of proteins, although little is known about how mutated proteins are adapted in existing developmental programs. Here we investigate the biological effects of a variant of the GLI3 transcription factor (GLI3[R1537C]) carried in Neanderthals and Denisovans, which are extinct hominins close to modern humans. R1537C does not compromise protein stability or GLI3 activator-dependent transcriptional activities. In contrast, R1537C affects the regulation of downstream target genes associated with developmental processes. Furthermore, genome-edited mice carrying the Neanderthal/Denisovan GLI3 mutation exhibited various alterations in skeletal morphology. Our data suggest that an extinct hominin-type GLI3 contributes to species-specific anatomical variations, which were tolerated by relaxed constraint in developmental programs during human evolution.},
}

@article {pmid38012927,
year = {2023},
author = {Lee, OY and Wu, HHT and Besra, GS and Minnikin, DE and Jaeger, HY and Maixner, F and Zink, A and Gasparik, M and Pap, I and Bereczki, Z and Pálfi, G},
title = {Sensitive lipid biomarker detection for tuberculosis in late Neanderthal skeletons from Subalyuk Cave, Hungary.},
journal = {Tuberculosis (Edinburgh, Scotland)},
volume = {143S},
number = {},
pages = {102420},
doi = {10.1016/j.tube.2023.102420},
pmid = {38012927},
issn = {1873-281X},
mesh = {Adult ; Child ; Humans ; Female ; Child, Preschool ; Animals ; *Neanderthals/genetics ; Hungary ; *Mycobacterium tuberculosis/genetics ; DNA, Bacterial/genetics ; *Tuberculosis/diagnosis ; Skeleton/chemistry ; Biomarkers/analysis ; Lipids/analysis ; },
abstract = {Skeletal remains of two Neanderthal individuals, a 25-35 year-old woman and a 3-4 year-old child, were discovered in a Subalyuk Cave in North-Eastern Hungary. Radiocarbon dating of the female and child remains revealed an age of 39,732-39,076 and 36,117-35,387 cal BP, respectively. Paleopathological studies of these Neanderthal remains revealed probable evidence of skeletal mycobacterial infection, including in the sacrum of the adult specimen and the endocranial surface of the child's skull. Application of PCR amplification to the juvenile cranium and a vertebra gave a positive result (IS6110) for tuberculosis, backed up by spoligotyping. Lipid biomarker analyses of the same two specimens revealed definitive signals for C32 mycoserosates, a very characteristic component of the Mycobacterium tuberculosis complex (MTBC). A vertebra from the adult provided weak evidence for mycocerosate biomarkers. The correlation of probable skeletal lesions with characteristic amplified DNA fragments and a proven lipid biomarker points to the presence of tuberculosis in these Neanderthals. In particular, the closely similar biomarker profiles, for two distinct juvenile cranial and vertebral bones, strengthen this diagnosis.},
}

Adult
Child
Humans
Female
Child, Preschool
Animals
*Neanderthals/genetics
Hungary
*Mycobacterium tuberculosis/genetics
DNA, Bacterial/genetics
*Tuberculosis/diagnosis
Skeleton/chemistry
Biomarkers/analysis
Lipids/analysis

@article {pmid38012926,
year = {2023},
author = {Pálfi, G and Molnár, E and Bereczki, Z and Coqueugniot, H and Dutour, O and Tillier, AM and Rosendahl, W and Sklánitz, A and Mester, Z and Gasparik, M and Maixner, F and Zink, A and Minnikin, DE and Pap, I},
title = {Re-examination of the Subalyuk Neanderthal remains uncovers signs of probable TB infection (Subalyuk Cave, Hungary).},
journal = {Tuberculosis (Edinburgh, Scotland)},
volume = {143S},
number = {},
pages = {102419},
doi = {10.1016/j.tube.2023.102419},
pmid = {38012926},
issn = {1873-281X},
mesh = {Young Adult ; Humans ; Female ; Child, Preschool ; Animals ; *Mycobacterium tuberculosis ; *Neanderthals ; Hungary ; *Tuberculosis ; Bone and Bones ; Paleopathology/methods ; },
abstract = {In 1932, skeletal remains of two Neanderthal individuals, a young adult female and a 3-4-year-old child, were discovered in Subalyuk Cave in Northern Hungary [1,2]. Results of the anthropological examination were published some years after this important discovery. Methodological progress encouraged re-examination of the material during the last few years. Radiocarbon dating revealed a chronological age of 39,732-39,076 cal. BP for the adult female and 36,117-35,387 cal. BP for the child [3]. Morphological paleopathological studies of these Neanderthal remains uncovered distinct evidence of skeletal infections. Alterations of the adult individual's sacrum suggest probable early-stage sacroiliitis, while several vertebral bodies indicate superficial osseous remodelling of infectious origin. Traces of pathological lesions were observed on the endocranial surface of the child's skull, reflecting a reaction of meningeal tissues, a consequence of a probable TB-related meningeal infectious process. Results of recent paleomicrobiological examinations - lipid biomarker and aDNA studies - support the morphological diagnosis of probable TB infections [4].},
}

Young Adult
Humans
Female
Child, Preschool
Animals
*Mycobacterium tuberculosis
*Neanderthals
Hungary
*Tuberculosis
Bone and Bones
Paleopathology/methods

@article {pmid37992125,
year = {2023},
author = {Di Santo, LN and Quilodrán, CS and Currat, M},
title = {Temporal Variation in Introgressed Segments' Length Statistics Computed from a Limited Number of Ancient Genomes Sheds Light on Past Admixture Pulses.},
journal = {Molecular biology and evolution},
volume = {40},
number = {12},
pages = {},
pmid = {37992125},
issn = {1537-1719},
mesh = {Animals ; *Genomics ; Paleontology ; *Neanderthals/genetics ; Genome ; Biological Evolution ; },
abstract = {Hybridization is recognized as an important evolutionary force, but identifying and timing admixture events between divergent lineages remain a major aim of evolutionary biology. While this has traditionally been done using inferential tools on contemporary genomes, the latest advances in paleogenomics have provided a growing wealth of temporally distributed genomic data. Here, we used individual-based simulations to generate chromosome-level genomic data for a 2-population system and described temporal neutral introgression patterns under a single- and 2-pulse admixture model. We computed 6 summary statistics aiming to inform the timing and number of admixture pulses between interbreeding entities: lengths of introgressed sequences and their variance within genomes, as well as genome-wide introgression proportions and related measures. The first 2 statistics could confidently be used to infer interlineage hybridization history, peaking at the beginning and shortly after an admixture pulse. Temporal variation in introgression proportions and related statistics provided more limited insights, particularly when considering their application to ancient genomes still scant in number. Lastly, we computed these statistics on Homo sapiens paleogenomes and successfully inferred the hybridization pulse from Neanderthal that occurred approximately 40 to 60 kya. The scarce number of genomes dating from this period prevented more precise inferences, but the accumulation of paleogenomic data opens promising perspectives as our approach only requires a limited number of ancient genomes.},
}

Animals
*Genomics
Paleontology
*Neanderthals/genetics
Genome
Biological Evolution

@article {pmid37989099,
year = {2023},
author = {Ragsdale, AP},
title = {Human evolution: Neanderthal footprints in African genomes.},
journal = {Current biology : CB},
volume = {33},
number = {22},
pages = {R1197-R1200},
doi = {10.1016/j.cub.2023.10.005},
pmid = {37989099},
issn = {1879-0445},
mesh = {Animals ; Humans ; Alleles ; *Evolution, Molecular ; Gene Flow ; *Genome, Human ; Genomics ; *Neanderthals/genetics ; Selection, Genetic ; African People ; },
abstract = {Human and Neanderthal populations met and mixed on multiple occasions over evolutionary time, resulting in the exchange of genetic material. New genomic analyses of diverse African populations reveal a history of bidirectional gene flow and selection acting on introgressed alleles.},
}

Animals
Humans
Alleles
*Evolution, Molecular
Gene Flow
*Genome, Human
Genomics
*Neanderthals/genetics
Selection, Genetic
African People

@article {pmid37977419,
year = {2023},
author = {Urnikyte, A and Masiulyte, A and Pranckeniene, L and Kučinskas, V},
title = {Disentangling archaic introgression and genomic signatures of selection at human immunity genes.},
journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases},
volume = {116},
number = {},
pages = {105528},
doi = {10.1016/j.meegid.2023.105528},
pmid = {37977419},
issn = {1567-7257},
mesh = {Humans ; Animals ; Evolution, Molecular ; *Neanderthals/genetics ; Genomics ; Genome, Human ; *Communicable Diseases/genetics ; Selection, Genetic ; },
abstract = {Pathogens and infectious diseases have imposed exceptionally strong selective pressure on ancient and modern human genomes and contributed to the current variation in many genes. There is evidence that modern humans acquired immune variants through interbreeding with ancient hominins, but the impact of such variants on human traits is not fully understood. The main objectives of this research were to infer the genetic signatures of positive selection that may be involved in adaptation to infectious diseases and to investigate the function of Neanderthal alleles identified within a set of 50 Lithuanian genomes. Introgressed regions were identified using the machine learning tool ArchIE. Recent positive selection signatures were analysed using iHS. We detected high-scoring signals of positive selection at innate immunity genes (EMB, PARP8, HLAC, and CDSN) and evaluated their interactions with the structural proteins of pathogens. Interactions with human immunodeficiency virus (HIV) 1 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were identified. Overall, genomic regions introgressed from Neanderthals were shown to be enriched in genes related to immunity, keratinocyte differentiation, and sensory perception.},
}

Humans
Animals
Evolution, Molecular
*Neanderthals/genetics
Genomics
Genome, Human
*Communicable Diseases/genetics
Selection, Genetic

@article {pmid37925533,
year = {2023},
author = {Raja, A and Kuiper, JJW},
title = {Evolutionary immuno-genetics of endoplasmic reticulum aminopeptidase II (ERAP2).},
journal = {Genes and immunity},
volume = {24},
number = {6},
pages = {295-302},
pmid = {37925533},
issn = {1476-5470},
support = {954992//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (H2020 Excellent Science - Marie Skłodowska-Curie Actions)/ ; },
mesh = {Humans ; *Aminopeptidases/genetics/immunology ; Autoimmune Diseases/genetics/immunology ; *Endoplasmic Reticulum/enzymology ; Haplotypes ; Minor Histocompatibility Antigens/genetics ; *Evolution, Molecular ; *Adaptive Immunity/genetics ; },
abstract = {Endoplasmic reticulum aminopeptidase 2 (ERAP2) is a proteolytic enzyme involved in adaptive immunity. The ERAP2 gene is highly polymorphic and encodes haplotypes that confer resistance against lethal infectious diseases, but also increase the risk for autoimmune disorders. Identifying how ERAP2 influences susceptibility to these traits requires an understanding of the selective pressures that shaped and maintained allelic variation throughout human evolution. Our review discusses the genetic regulation of haplotypes and diversity in naturally occurring ERAP2 allotypes in the global population. We outline how these ERAP2 haplotypes evolved during human history and highlight the presence of Neanderthal DNA sequences in ERAP2 of modern humans. Recent evidence suggests that human adaptation during the last ~10,000 years and historic pandemics left a significant mark on the ERAP2 gene that determines susceptibility to infectious and inflammatory diseases today.},
}

Humans
*Aminopeptidases/genetics/immunology
Autoimmune Diseases/genetics/immunology
*Endoplasmic Reticulum/enzymology
Haplotypes
Minor Histocompatibility Antigens/genetics
*Evolution, Molecular
*Adaptive Immunity/genetics

@article {pmid37851812,
year = {2023},
author = {Quilodrán, CS and Rio, J and Tsoupas, A and Currat, M},
title = {Past human expansions shaped the spatial pattern of Neanderthal ancestry.},
journal = {Science advances},
volume = {9},
number = {42},
pages = {eadg9817},
pmid = {37851812},
issn = {2375-2548},
mesh = {Animals ; Humans ; Africa ; Asian People ; Hominidae/genetics ; *Neanderthals/genetics ; *Phylogeography ; European People/genetics ; *Genetic Introgression/genetics ; },
abstract = {The worldwide expansion of modern humans (Homo sapiens) started before the extinction of Neanderthals (Homo neanderthalensis). Both species coexisted and interbred, leading to slightly higher introgression in East Asians than in Europeans. This distinct ancestry level has been argued to result from selection, but range expansions of modern humans could provide an alternative explanation. This hypothesis would lead to spatial introgression gradients, increasing with distance from the expansion source. We investigate the presence of Neanderthal introgression gradients after past human expansions by analyzing Eurasian paleogenomes. We show that the out-of-Africa expansion resulted in spatial gradients of Neanderthal ancestry that persisted through time. While keeping the same gradient orientation, the expansion of early Neolithic farmers contributed decisively to reducing the Neanderthal introgression in European populations compared to Asian populations. This is because Neolithic farmers carried less Neanderthal DNA than preceding Paleolithic hunter-gatherers. This study shows that inferences about past human population dynamics can be made from the spatiotemporal variation in archaic introgression.},
}

Animals
Humans
Africa
Asian People
Hominidae/genetics
*Neanderthals/genetics
*Phylogeography
European People/genetics
*Genetic Introgression/genetics

@article {pmid37846608,
year = {2024},
author = {Chen, Y and Yu, XY and Xu, SJ and Shi, XQ and Zhang, XX and Sun, C},
title = {An indel introduced by Neanderthal introgression, rs3835124:ATTTATT > ATT, might contribute to prostate cancer risk by regulating PDK1 expression.},
journal = {Annals of human genetics},
volume = {88},
number = {2},
pages = {126-137},
doi = {10.1111/ahg.12533},
pmid = {37846608},
issn = {1469-1809},
support = {//National Natural Science Foundation of China/ ; //Fundamental Research Funds for the Central Universities/ ; },
mesh = {Humans ; Animals ; *Neanderthals/genetics ; Genome-Wide Association Study ; Genetics, Population ; Phylogeny ; Haplotypes ; Genome, Human ; *Neoplasms/genetics ; },
abstract = {INTRODUCTION: Prostate cancer is one of the most common cancer types in males and rs12621278:A > G has been suggested to be associated with this disease by previous genome-wide association studies. One thousand genomes project data analysis indicated that rs12621278:A > G is within two long-core haplotypes. However, the origin, causal variant(s), and molecular function of these haplotypes were remaining unclear.

MATERIALS AND METHODS: Population genetics analysis and functional genomics work was performed for this locus.

RESULTS: Phylogeny analysis verified that the rare haplotype is derived from Neanderthal introgression. Genome annotation suggested that three genetic variants in the core haplotypes, rs116108611:G > A, rs139972066:AAAAAAAA > AAAAAAAAA, and rs3835124:ATTTATT > ATT, are located in functional regions. Luciferase assay indicated that rs139972066:AAAAAAAA > AAAAAAAAA and rs116108611:G > A are not able to alter ITGA6 (integrin alpha 6) and ITGA6 antisense RNA 1 expression, respectively. In contrast, rs3835124:ATTTATT > ATT can significantly influence PDK1 (pyruvate dehydrogenase kinase 1) expression, which was verified by expression quantitative trait locus analysis. This genetic variant can alter transcription factor cut like homeobox 1 interaction efficiency. The introgressed haplotype was observed to be subject to positive selection in East Asian populations. The molecular function of the haplotype suggested that Neanderthal should be with lower PDK1 expression and further different energy homeostasis from modern human.

CONCLUSION: This study provided new insight into the contribution of Neanderthal introgression to human phenotypes.},
}

Humans
Animals
*Neanderthals/genetics
Genome-Wide Association Study
Genetics, Population
Phylogeny
Haplotypes
Genome, Human
*Neoplasms/genetics

@article {pmid37837965,
year = {2023},
author = {Harris, DN and Platt, A and Hansen, MEB and Fan, S and McQuillan, MA and Nyambo, T and Mpoloka, SW and Mokone, GG and Belay, G and Fokunang, C and Njamnshi, AK and Tishkoff, SA},
title = {Diverse African genomes reveal selection on ancient modern human introgressions in Neanderthals.},
journal = {Current biology : CB},
volume = {33},
number = {22},
pages = {4905-4916.e5},
pmid = {37837965},
issn = {1879-0445},
support = {R01 AR076241/AR/NIAMS NIH HHS/United States ; R35 GM134957/GM/NIGMS NIH HHS/United States ; T32 DK007314/DK/NIDDK NIH HHS/United States ; },
mesh = {Humans ; Animals ; *Neanderthals/genetics ; Genome, Human ; Gene Flow ; Genomics ; Africa South of the Sahara ; },
abstract = {Comparisons of Neanderthal genomes to anatomically modern human (AMH) genomes show a history of Neanderthal-to-AMH introgression stemming from interbreeding after the migration of AMHs from Africa to Eurasia. All non-sub-Saharan African AMHs have genomic regions genetically similar to Neanderthals that descend from this introgression. Regions of the genome with Neanderthal similarities have also been identified in sub-Saharan African populations, but their origins have been unclear. To better understand how these regions are distributed across sub-Saharan Africa, the source of their origin, and what their distribution within the genome tells us about early AMH and Neanderthal evolution, we analyzed a dataset of high-coverage, whole-genome sequences from 180 individuals from 12 diverse sub-Saharan African populations. In sub-Saharan African populations with non-sub-Saharan African ancestry, as much as 1% of their genomes can be attributed to Neanderthal sequence introduced by recent migration, and subsequent admixture, of AMH populations originating from the Levant and North Africa. However, most Neanderthal homologous regions in sub-Saharan African populations originate from migration of AMH populations from Africa to Eurasia ∼250 kya, and subsequent admixture with Neanderthals, resulting in ∼6% AMH ancestry in Neanderthals. These results indicate that there have been multiple migration events of AMHs out of Africa and that Neanderthal and AMH gene flow has been bi-directional. Observing that genomic regions where AMHs show a depletion of Neanderthal introgression are also regions where Neanderthal genomes show a depletion of AMH introgression points to deleterious interactions between introgressed variants and background genomes in both groups-a hallmark of incipient speciation.},
}

Humans
Animals
*Neanderthals/genetics
Genome, Human
Gene Flow
Genomics
Africa South of the Sahara

@article {pmid37828055,
year = {2023},
author = {Russo, G and Milks, A and Leder, D and Koddenberg, T and Starkovich, BM and Duval, M and Zhao, JX and Darga, R and Rosendahl, W and Terberger, T},
title = {First direct evidence of lion hunting and the early use of a lion pelt by Neanderthals.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {16405},
pmid = {37828055},
issn = {2045-2322},
mesh = {Animals ; Humans ; *Neanderthals ; *Lions ; Hunting ; Archaeology ; *Hominidae ; *Panthera ; Fossils ; },
abstract = {During the Upper Paleolithic, lions become an important theme in Paleolithic art and are more frequent in anthropogenic faunal assemblages. However, the relationship between hominins and lions in earlier periods is poorly known and primarily interpreted as interspecies competition. Here we present new evidence for Neanderthal-cave lion interactions during the Middle Paleolithic. We report new evidence of hunting lesions on the 48,000 old cave lion skeleton found at Siegsdorf (Germany) that attest to the earliest direct instance of a large predator kill in human history. A comparative analysis of a partial puncture to a rib suggests that the fatal stab was delivered with a wooden thrusting spear. We also present the discovery of distal lion phalanges at least 190,000 old from Einhornhöhle (Germany), representing the earliest example of the use of cave lion skin by Neanderthals in Central Europe. Our study provides novel evidence on a new dimension of Neanderthal behavioral complexity.},
}

Animals
Humans
*Neanderthals
*Lions
Hunting
Archaeology
*Hominidae
*Panthera
Fossils

@article {pmid37816865,
year = {2023},
author = {Faux, P and Ding, L and Ramirez-Aristeguieta, LM and Chacón-Duque, JC and Comini, M and Mendoza-Revilla, J and Fuentes-Guajardo, M and Jaramillo, C and Arias, W and Hurtado, M and Villegas, V and Granja, V and Barquera, R and Everardo-Martínez, P and Quinto-Sánchez, M and Gómez-Valdés, J and Villamil-Ramírez, H and Silva de Cerqueira, CC and Hünemeier, T and Ramallo, V and Gonzalez-José, R and Schüler-Faccini, L and Bortolini, MC and Acuña-Alonzo, V and Canizales-Quinteros, S and Poletti, G and Gallo, C and Rothhammer, F and Rojas, W and Schmid, AB and Adhikari, K and Bennett, DL and Ruiz-Linares, A},
title = {Neanderthal introgression in SCN9A impacts mechanical pain sensitivity.},
journal = {Communications biology},
volume = {6},
number = {1},
pages = {958},
pmid = {37816865},
issn = {2399-3642},
support = {MR/W002388/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; 223149/Z/21/Z/WT_/Wellcome Trust/United Kingdom ; 222101/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; MR/T020113/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; /VAC_/Versus Arthritis/United Kingdom ; BB/I021213/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {Humans ; Animals ; *Pain Threshold ; *Neanderthals/genetics ; Pain/genetics ; NAV1.7 Voltage-Gated Sodium Channel/genetics ; Nociception ; },
abstract = {The Nav1.7 voltage-gated sodium channel plays a key role in nociception. Three functional variants in the SCN9A gene (encoding M932L, V991L, and D1908G in Nav1.7), have recently been identified as stemming from Neanderthal introgression and to associate with pain symptomatology in UK BioBank data. In 1000 genomes data, these variants are absent in Europeans but common in Latin Americans. Analysing high-density genotype data from 7594 Latin Americans, we characterized Neanderthal introgression in SCN9A. We find that tracts of introgression occur on a Native American genomic background, have an average length of ~123 kb and overlap the M932L, V991L, and D1908G coding positions. Furthermore, we measured experimentally six pain thresholds in 1623 healthy Colombians. We found that Neanderthal ancestry in SCN9A is significantly associated with a lower mechanical pain threshold after sensitization with mustard oil and evidence of additivity of effects across Nav1.7 variants. Our findings support the reported association of Neanderthal Nav1.7 variants with clinical pain, define a specific sensory modality affected by archaic introgression in SCN9A and are consistent with independent effects of the Neanderthal variants on Nav1.7 function.},
}

Humans
Animals
*Pain Threshold
*Neanderthals/genetics
Pain/genetics
NAV1.7 Voltage-Gated Sodium Channel/genetics
Nociception

@article {pmid37808839,
year = {2024},
author = {Villanea, FA and Peede, D and Kaufman, EJ and Añorve-Garibay, V and Chevy, ET and Villa-Islas, V and Witt, KE and Zeloni, R and Marnetto, D and Moorjani, P and Jay, F and Valdmanis, PN and Ávila-Arcos, MC and Huerta-Sánchez, E},
title = {The MUC19 gene in Denisovans, Neanderthals, and Modern Humans: An Evolutionary History of Recurrent Introgression and Natural Selection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.09.25.559202},
pmid = {37808839},
issn = {2692-8205},
support = {R35 GM142978/GM/NIGMS NIH HHS/United States ; },
abstract = {UNLABELLED: We study the gene MUC19, for which modern humans carry a Denisovan-like haplotype. MUC19 is a mucin, a glycoprotein that forms gels with various biological functions. We find the diagnostic variants for the Denisovan-like MUC19 haplotype at high frequencies in admixed Latin American individuals among global populations, and at highest frequency in 23 ancient Indigenous American individuals, all predating population admixture with Europeans and Africans. We find that the Denisovan-like MUC19 haplotype carries a higher copy number of a 30 base-pair variable number tandem repeat, and that copy numbers of this repeat are exceedingly high in American populations and are under positive selection. This study provides the first example of positive selection acting on archaic alleles at coding sites and VNTRs. Finally, we find that some Neanderthals carry the Denisovan-like MUC19 haplotype, and that it was likely introgressed into human populations through Neanderthal introgression rather than Denisovan introgression.

ONE-SENTENCE SUMMARY: Modern humans and Neanderthals carry a Denisovan variant of the MUC19 gene, which is under positive selection in populations of Indigenous American ancestry.},
}

@article {pmid37794824,
year = {2024},
author = {Carretero, JM and Rodríguez, L and García-González, R and Arsuaga, JL},
title = {Main morphological characteristics and sexual dimorphism of hominin adult femora from the Sima de los Huesos Middle Pleistocene site (Sierra de Atapuerca, Spain).},
journal = {Anatomical record (Hoboken, N.J. : 2007)},
volume = {307},
number = {7},
pages = {2575-2605},
doi = {10.1002/ar.25331},
pmid = {37794824},
issn = {1932-8494},
support = {PID2021-122355NB-C31//Ministerio de Ciencia, Innovación y Universidades/ ; //MCIN/AEI// ; //Junta de Castilla y León/ ; //Fundación Atapuerca/ ; },
mesh = {Animals ; *Femur/anatomy & histology ; Female ; *Sex Characteristics ; Male ; *Fossils/anatomy & histology ; Spain ; *Hominidae/anatomy & histology ; Neanderthals/anatomy & histology ; Biological Evolution ; Humans ; },
abstract = {The excellent fossil record from Sima de los Huesos (SH) includes three well-known complete adult femora and several partial specimens that have not yet been published in detail. This fossil record provides an opportunity to analyze the morphology of European pre-Neandertal adult femur and its variation with different evolution patterns. Currently, there are a minimum of five adult individuals (males or females). In this study, we compiled previously published basic anatomical and biometric characteristics of SH adult femora, emphasizing the most relevant features compared to other recent and fossil hominins. The SH femora exhibited a primitive morphological pattern common to all non-Homo sapiens femora, as well as most of the Neandertal traits. Therefore, the complete Upper Pleistocene Neandertal pattern was well-established in Middle Pleistocene ancestors long before the proper Neandertals appeared. Additionally, we highlight that the SH and Neandertal femora share some morphological traits and proportions with modern humans that hold sexual significance in our species, regardless of size. Keeping this in mind, we discussed the sex determination of the complete SH specimens and re-evaluated sex allocation in two of them.},
}

Animals
*Femur/anatomy & histology
Female
*Sex Characteristics
Male
*Fossils/anatomy & histology
Spain
*Hominidae/anatomy & histology
Neanderthals/anatomy & histology
Biological Evolution
Humans

@article {pmid37790518,
year = {2023},
author = {Yee, SW and Ferrández-Peral, L and Alentorn, P and Fontsere, C and Ceylan, M and Koleske, ML and Handin, N and Artegoitia, VM and Lara, G and Chien, HC and Zhou, X and Dainat, J and Zalevsky, A and Sali, A and Brand, CM and Capra, JA and Artursson, P and Newman, JW and Marques-Bonet, T and Giacomini, KM},
title = {Illuminating the Function of the Orphan Transporter, SLC22A10 in Humans and Other Primates.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {37790518},
issn = {2693-5015},
support = {R01 GM117163/GM/NIGMS NIH HHS/United States ; R01 GM139875/GM/NIGMS NIH HHS/United States ; },
abstract = {SLC22A10 is classified as an orphan transporter with unknown substrates and function. Here we describe the discovery of the substrate specificity and functional characteristics of SLC22A10. The human SLC22A10 tagged with green fluorescent protein was found to be absent from the plasma membrane, in contrast to the SLC22A10 orthologs found in great apes. Estradiol-17β-glucuronide accumulated in cells expressing great ape SLC22A10 orthologs (over 4-fold, p<0.001). In contrast, human SLC22A10 displayed no uptake function. Sequence alignments revealed two amino acid differences including a proline at position 220 of the human SLC22A10 and a leucine at the same position of great ape orthologs. Site-directed mutagenesis yielding the human SLC22A10-P220L produced a protein with excellent plasma membrane localization and associated uptake function. Neanderthal and Denisovan genomes show human-like sequences at proline 220 position, corroborating that SLC22A10 were rendered nonfunctional during hominin evolution after the divergence from the pan lineage (chimpanzees and bonobos). These findings demonstrate that human SLC22A10 is a unitary pseudogene and was inactivated by a missense mutation that is fixed in humans, whereas orthologs in great apes transport sex steroid conjugates.},
}

@article {pmid37747127,
year = {2023},
author = {Hui, J and Balzeau, A},
title = {The diploic venous system in Homo neanderthalensis and fossil Homo sapiens: A study using high-resolution computed tomography.},
journal = {American journal of biological anthropology},
volume = {182},
number = {3},
pages = {412-427},
doi = {10.1002/ajpa.24843},
pmid = {37747127},
issn = {2692-7691},
support = {ANR-20-CE27-0009//Agence Nationale de la Recherche/ ; //China Scholarship Council/ ; },
abstract = {OBJECTIVES: The diploic venous system has been hypothesized to be related to human brain evolution, though its evolutionary trajectory and physiological functions remain largely unclear. This study examines the characteristics of the diploic venous channels (DCs) in a selection of well-preserved Homo neanderthalensis and Upper Paleolithic Homo sapiens crania, searching for the differences between the two taxa and exploring the associations between brain anatomy and DCs.

MATERIALS AND METHODS: Five H. neanderthalensis and four H. sapiens fossil specimens from Western Europe were analyzed. Based on Micro-CT scanning and 3D reconstruction, the distribution pattern and draining orifices of the DCs were inspected qualitatively. The size of the DCs was quantified by volume calculation, and the degree of complexity was quantified by fractal analyses.

RESULTS: High-resolution data show the details of the DC structures not documented in previous studies. H. neanderthalensis and H. sapiens specimens share substantial similarities in the DCs. The noticeable differences between the two samples manifest in the connecting points surrounding the frontal sinuses, parietal foramina, and asterional area.

DISCUSSION: This study provides a better understanding of the anatomy of the DCs in H. neanderthalensis and H. sapiens. The connection patterns of the DCs have potential utility in distinguishing between the two taxa and in the phylogenetic and taxonomic discussion of the Neandertal-like specimens with controversial taxonomic status.},
}

@article {pmid37738342,
year = {2023},
author = {Vidal-Cordasco, M and Terlato, G and Ocio, D and Marín-Arroyo, AB},
title = {Neanderthal coexistence with Homo sapiens in Europe was affected by herbivore carrying capacity.},
journal = {Science advances},
volume = {9},
number = {38},
pages = {eadi4099},
pmid = {37738342},
issn = {2375-2548},
mesh = {Humans ; Animals ; *Neanderthals ; Herbivory ; Bayes Theorem ; Conservation of Natural Resources ; Ecosystem ; Europe ; },
abstract = {It has been proposed that climate change and the arrival of modern humans in Europe affected the disappearance of Neanderthals due to their impact on trophic resources; however, it has remained challenging to quantify the effect of these factors. By using Bayesian age models to derive the chronology of the European Middle to Upper Paleolithic transition, followed by a dynamic vegetation model that provides the Net Primary Productivity, and a macroecological model to compute herbivore abundance, we show that in continental regions where the ecosystem productivity was low or unstable, Neanderthals disappeared before or just after the arrival of Homo sapiens. In contrast, regions with high and stable productivity witnessed a prolonged coexistence between both species. The temporal overlap between Neanderthals and H. sapiens is significantly correlated with the carrying capacity of small- and medium-sized herbivores. These results suggest that herbivore abundance released the trophic pressure of the secondary consumers guild, which affected the coexistence likelihood between both human species.},
}

Humans
Animals
*Neanderthals
Herbivory
Bayes Theorem
Conservation of Natural Resources
Ecosystem
Europe

@article {pmid37737280,
year = {2023},
author = {Fajardo, S and Kozowyk, PRB and Langejans, GHJ},
title = {Measuring ancient technological complexity and its cognitive implications using Petri nets.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {14961},
pmid = {37737280},
issn = {2045-2322},
mesh = {Humans ; Animals ; *Neanderthals ; Archaeology ; Benchmarking ; Cognition ; Receptor Protein-Tyrosine Kinases ; Technology ; },
abstract = {We implement a method from computer sciences to address a challenge in Paleolithic archaeology: how to infer cognition differences from material culture. Archaeological material culture is linked to cognition, and more complex ancient technologies are assumed to have required complex cognition. We present an application of Petri net analysis to compare Neanderthal tar production technologies and tie the results to cognitive requirements. We applied three complexity metrics, each relying on their own unique definitions of complexity, to the modeled production processes. Based on the results, we propose that Neanderthal technical cognition may have been analogous to that of contemporary modern humans. This method also enables us to distinguish the high-order cognitive functions combining traits like planning, inhibitory control, and learning that were likely required by different ancient technological processes. The Petri net approach can contribute to our understanding of technology and cognitive evolution as it can be used on different materials and technologies, across time and species.},
}

Humans
Animals
*Neanderthals
Archaeology
Benchmarking
Cognition
Receptor Protein-Tyrosine Kinases
Technology

@article {pmid37713634,
year = {2023},
author = {Ge, X and Lu, Y and Chen, S and Gao, Y and Ma, L and Liu, L and Liu, J and Ma, X and Kang, L and Xu, S},
title = {Genetic Origins and Adaptive Evolution of the Deng People on the Tibetan Plateau.},
journal = {Molecular biology and evolution},
volume = {40},
number = {10},
pages = {},
pmid = {37713634},
issn = {1537-1719},
mesh = {Adaptor Proteins, Signal Transducing ; Tibet ; East Asian People ; *Asian People/genetics ; Haplotypes ; Humans ; Altitude ; },
abstract = {The Tibetan Plateau is populated by diverse ethnic groups, but most of them are underrepresented in genomics studies compared with the Tibetans (TIB). Here, to gain further insight into the genetic diversity and evolutionary history of the people living in the Tibetan Plateau, we sequenced 54 whole genomes of the Deng people with high coverage (30-60×) and analyzed the data together with that of TIB and Sherpas, as well as 968 ancient Asian genomes and available archaic and modern human data. We identified 17.74 million novel single-nucleotide variants from the newly sequenced genomes, although the Deng people showed reduced genomic diversity and a relatively small effective population size. Compared with the other Tibetan highlander groups which are highly admixed, the Deng people are dominated by a sole ancestry that could be traced to some ancient northern East Asian populations. The divergence between Deng and Tibetan people (∼4,700-7,200 years) was more recent than that between highlanders and the Han Chinese (Deng-HAN, ∼9,000-14,000 years; TIB-HAN, 7,200-10,000 years). Adaptive genetic variants (AGVs) identified in the Deng are only partially shared with those previously reported in the TIB like HLA-DQB1, whereas others like KLHL12 were not reported in TIB. In contrast, the top candidate genes harboring AGVs as previously identified in TIB, like EPAS1 and EGLN1, do not show strong positive selection signals in Deng. Interestingly, Deng also showed a different archaic introgression scenario from that observed in the TIB. Our results suggest that convergent adaptation might be prevalent on the Tibetan Plateau.},
}

Adaptor Proteins, Signal Transducing
Tibet
East Asian People
*Asian People/genetics
Haplotypes
Humans
Altitude

@article {pmid37679497,
year = {2023},
author = {Kozowyk, PRB and Fajardo, S and Langejans, GHJ},
title = {Scaling Palaeolithic tar production processes exponentially increases behavioural complexity.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {14709},
pmid = {37679497},
issn = {2045-2322},
mesh = {Humans ; Animals ; *Neanderthals ; Cognition ; Archaeology ; Commerce ; Food Handling ; Tars ; },
abstract = {Technological processes, reconstructed from the archaeological record, are used to study the evolution of behaviour and cognition of Neanderthals and early modern humans. In comparisons, technologies that are more complex infer more complex behaviour and cognition. The manufacture of birch bark tar adhesives is regarded as particularly telling and often features in debates about Neanderthal cognition. One method of tar production, the 'condensation technique', demonstrates a pathway for Neanderthals to have discovered birch bark tar. However, to improve on the relatively low yield, and to turn tar into a perennial innovation, this method likely needed to be scaled up. Yet, it is currently unknown how scaling Palaeolithic technological processes influences their complexity. We used Petri net models and the Extended Cyclomatic Metric to measure system complexity of birch tar production with a single and three concurrent condensation assemblies. Our results show that changing the number of concurrent tar production assemblies substantially increases the measured complexity. This has potential implications on the behavioural and cognitive capacities required by Neanderthals, such as an increase in cooperation or inhibition control.},
}

Humans
Animals
*Neanderthals
Cognition
Archaeology
Commerce
Food Handling
Tars

@article {pmid37675658,
year = {2024},
author = {Mester, Z and Coqueugniot, H and Tillier, AM and Rosendahl, W and Friedrich, R and Zink, A and Maixner, F and Dutour, O and Bereczki, Z and Gasparik, M and Pap, I and Pálfi, G},
title = {First direct dating of the Late Neanderthal remains from Subalyuk Cave in Northern Hungary.},
journal = {Anthropologischer Anzeiger; Bericht uber die biologisch-anthropologische Literatur},
volume = {81},
number = {2},
pages = {169-181},
doi = {10.1127/anthranz/2023/1716},
pmid = {37675658},
issn = {0003-5548},
mesh = {Animals ; Child ; Humans ; *Neanderthals ; Hungary ; Fossils ; *Hominidae ; Europe ; Archaeology ; Radiometric Dating ; },
abstract = {The Subalyuk hominin remains were uncovered in 1932 in a cave of the same name in the Bükk Mountains, near the village of Cserépfalu in Borsod-Abaúj-Zemplén County, Northern Hungary. The remains represent two individuals, an adult and a young child who have been described in a few publications since their discovery, providing substantial anthropological data and general assessments of their Neanderthal affiliation. They were associated with Late Mousterian industry. Thus, the Bükk Mountains gain importance in the discussion concerning the contribution of East Central European sites to the debate on the peopling history of Europe during the Late Middle to Early Upper Palaeolithic transition. In this paper, we summarize the archaeological and chronological context of the two individuals, and publish the first direct dating results that place them among the Last Neanderthals of Central Europe.},
}

Animals
Child
Humans
*Neanderthals
Hungary
Fossils
*Hominidae
Europe
Archaeology
Radiometric Dating

@article {pmid37660151,
year = {2023},
author = {Glunčić, M and Vlahović, I and Rosandić, M and Paar, V},
title = {Tandem NBPF 3mer HORs (Olduvai triplets) in Neanderthal and two novel HOR tandem arrays in human chromosome 1 T2T-CHM13 assembly.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {14420},
pmid = {37660151},
issn = {2045-2322},
mesh = {Humans ; Animals ; *Neanderthals/genetics ; Chromosomes, Human ; Chromosomes, Human, Pair 1 ; *Neuroblastoma ; Family ; Pan troglodytes ; },
abstract = {It is known that the ~ 1.6 kb Neuroblastoma BreakPoint Family (NBPF) repeats are human specific and contributing to cognitive capabilities, with increasing frequency in higher order repeat 3mer HORs (Olduvai triplets). From chimpanzee to modern human there is a discontinuous jump from 0 to ~ 50 tandemly organized 3mer HORs. Here we investigate the structure of NBPF 3mer HORs in the Neanderthal genome assembly of Pääbo et al., comparing it to the results obtained for human hg38.p14 chromosome 1. Our findings reveal corresponding NBPF 3mer HOR arrays in Neanderthals with slightly different monomer structures and numbers of HOR copies compared to humans. Additionally, we compute the NBPF 3mer HOR pattern for the complete telomere-to-telomere human genome assembly (T2T-CHM13) by Miga et al., identifying two novel tandem arrays of NBPF 3mer HOR repeats with 5 and 9 NBPF 3mer HOR copies. We hypothesize that these arrays correspond to novel NBPF genes (here referred to as NBPFA1 and NBPFA2). Further improving the quality of the Neanderthal genome using T2T-CHM13 as a reference would be of great interest in determining the presence of such distant novel NBPF genes in the Neanderthal genome and enhancing our understanding of human evolution.},
}

Humans
Animals
*Neanderthals/genetics
Chromosomes, Human
Chromosomes, Human, Pair 1
*Neuroblastoma
Family
Pan troglodytes

@article {pmid37659139,
year = {2023},
author = {Fiorenza, L and Habashi, W and Moggi-Cecchi, J and Benazzi, S and Sarig, R},
title = {Relationship between interproximal and occlusal wear in Australopithecus africanus and Neanderthal molars.},
journal = {Journal of human evolution},
volume = {183},
number = {},
pages = {103423},
doi = {10.1016/j.jhevol.2023.103423},
pmid = {37659139},
issn = {1095-8606},
mesh = {Humans ; Animals ; *Tooth Attrition ; *Neanderthals ; Molar ; *Tooth ; *Hominidae ; Fossils ; *Tooth Wear ; },
}

Humans
Animals
*Tooth Attrition
*Neanderthals
Molar
*Tooth
*Hominidae
Fossils
*Tooth Wear

@article {pmid37609337,
year = {2023},
author = {Yee, SW and Ferrández-Peral, L and Alentorn, P and Fontsere, C and Ceylan, M and Koleske, ML and Handin, N and Artegoitia, VM and Lara, G and Chien, HC and Zhou, X and Dainat, J and Zalevsky, A and Sali, A and Brand, CM and Capra, JA and Artursson, P and Newman, JW and Marques-Bonet, T and Giacomini, KM},
title = {Illuminating the Function of the Orphan Transporter, SLC22A10 in Humans and Other Primates.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37609337},
issn = {2692-8205},
support = {R01 GM117163/GM/NIGMS NIH HHS/United States ; R01 GM139875/GM/NIGMS NIH HHS/United States ; },
abstract = {SLC22A10 is classified as an orphan transporter with unknown substrates and function. Here we describe the discovery of the substrate specificity and functional characteristics of SLC22A10. The human SLC22A10 tagged with green fluorescent protein was found to be absent from the plasma membrane, in contrast to the SLC22A10 orthologs found in great apes. Estradiol-17β-glucuronide accumulated in cells expressing great ape SLC22A10 orthologs (over 4-fold, p<0.001). In contrast, human SLC22A10 displayed no uptake function. Sequence alignments revealed two amino acid differences including a proline at position 220 of the human SLC22A10 and a leucine at the same position of great ape orthologs. Site-directed mutagenesis yielding the human SLC22A10-P220L produced a protein with excellent plasma membrane localization and associated uptake function. Neanderthal and Denisovan genomes show human-like sequences at proline 220 position, corroborating that SLC22A10 were rendered nonfunctional during hominin evolution after the divergence from the pan lineage (chimpanzees and bonobos). These findings demonstrate that human SLC22A10 is a unitary pseudogene and was inactivated by a missense mutation that is fixed in humans, whereas orthologs in great apes transport sex steroid conjugates.},
}

@article {pmid37574541,
year = {2023},
author = {Piccardi, M and Gentiluomo, M and Bertoncini, S and Pezzilli, R and Erőss, B and Bunduc, S and Uzunoglu, FG and Talar-Wojnarowska, R and Vanagas, T and Sperti, C and Oliverius, M and Aoki, MN and Ermini, S and Hussein, T and Boggi, U and Jamroziak, K and Maiello, E and Morelli, L and Vodickova, L and Di Franco, G and Landi, S and Szentesi, A and Lovecek, M and Puzzono, M and Tavano, F and van Laarhoven, HWM and Zerbi, A and Mohelnikova-Duchonova, B and Stocker, H and Costello, E and Capurso, G and Ginocchi, L and Lawlor, RT and Vanella, G and Bazzocchi, F and Izbicki, JR and Latiano, A and Bueno-de-Mesquita, B and Ponz de Leon Pisani, R and Schöttker, B and Soucek, P and Hegyi, P and Gazouli, M and Hackert, T and Kupcinskas, J and Poskiene, L and Tacelli, M and Roth, S and Carrara, S and Perri, F and Hlavac, V and Theodoropoulos, GE and Busch, OR and Mambrini, A and van Eijck, CHJ and Arcidiacono, P and Scarpa, A and Pasquali, C and Basso, D and Lucchesi, M and Milanetto, AC and Neoptolemos, JP and Cavestro, GM and Janciauskas, D and Chen, X and Chammas, R and Goetz, M and Brenner, H and Archibugi, L and Dannemann, M and Canzian, F and Tofanelli, S and Campa, D},
title = {Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians.},
journal = {Biological research},
volume = {56},
number = {1},
pages = {46},
pmid = {37574541},
issn = {0717-6287},
support = {26881/CRUK_/Cancer Research UK/United Kingdom ; C7690/A26881/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Humans ; Animals ; *Neanderthals/genetics ; *Diabetes Mellitus, Type 2 ; Polymorphism, Single Nucleotide ; *Carcinoma, Pancreatic Ductal/genetics ; *Pancreatic Neoplasms/genetics ; },
abstract = {BACKGROUND: The genomes of present-day non-Africans are composed of 1-3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50-60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations.

RESULTS: The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19-1.54, P = 3.59 × 10[-6]), with a P-value close to a threshold that takes into account multiple testing.

CONCLUSIONS: Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.},
}

Humans
Animals
*Neanderthals/genetics
*Diabetes Mellitus, Type 2
Polymorphism, Single Nucleotide
*Carcinoma, Pancreatic Ductal/genetics
*Pancreatic Neoplasms/genetics