Viewport Size Code:
Login | Create New Account


About | Classical Genetics | Timelines | What's New | What's Hot

About | Classical Genetics | Timelines | What's New | What's Hot


Bibliography Options Menu

Hide Abstracts   |   Hide Additional Links
Long bibliographies are displayed in blocks of 100 citations at a time. At the end of each block there is an option to load the next block.

Bibliography on: Neanderthals

The Electronic Scholarly Publishing Project: Providing world-wide, free access to classic scientific papers and other scholarly materials, since 1993.


ESP: PubMed Auto Bibliography 25 Jun 2024 at 01:56 Created: 


Wikipedia: Neanderthals or Neandertals — named for the Neandertal region in Germany — were a species or subspecies of archaic human, in the genus Homo. Neanderthals became extinct around 40,000 years ago. They were closely related to modern humans, sharing 99.7% of DNA. Remains left by Neanderthals include bone and stone tools, which are found in Eurasia, from Western Europe to Central and Northern Asia. Neanderthals are generally classified by paleontologists as the species Homo neanderthalensis, having separated from the Homo sapiens lineage 600,000 years ago, but a minority consider them to be a subspecies of Homo sapiens (Homo sapiens neanderthalensis). Several cultural assemblages have been linked to the Neanderthals in Europe. The earliest, the Mousterian stone tool culture, dates to about 160,000 years ago. Late Mousterian artifacts were found in Gorham's Cave on the south-facing coast of Gibraltar. Compared to Homo sapiens, Neanderthals had a lower surface-to-volume ratio, with shorter legs and a bigger body, in conformance with Bergmann's rule, as an energy-loss reduction adaptation to life in a high-latitude (i.e. seasonally cold) climate. Their average cranial capacity was notably larger than typical for modern humans: 1600 cm3 vs. 1250-1400 cm3. The Neanderthal genome project published papers in 2010 and 2014 stating that Neanderthals contributed to the DNA of modern humans, including most humans outside sub-Saharan Africa, as well as a few populations in sub-Saharan Africa, through interbreeding, likely between 50,000 and 60,000 years ago.

Created with PubMed® Query: ( Neanderthal OR Neandertal ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2024-06-18
CmpDate: 2024-06-18

Yermakovich D, André M, Brucato N, et al (2024)

Denisovan admixture facilitated environmental adaptation in Papua New Guinean populations.

Proceedings of the National Academy of Sciences of the United States of America, 121(26):e2405889121.

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.

RevDate: 2024-06-07

Callaway E (2024)

These Neanderthal fire pits offer an extraordinarily precise snapshot of ancient life.

RevDate: 2024-05-29

Krämer K (2024)

Daily briefing: Neanderthals and humans made babies - briefly.

RevDate: 2024-06-03
CmpDate: 2024-05-28

Roca-Ayats N, Maceda I, Bruque CD, et al (2024)

Evolutionary and functional analyses of LRP5 in archaic and extant modern humans.

Human genomics, 18(1):53.

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.

RevDate: 2024-06-03

Iasi LNM, Chintalapati M, Skov L, et al (2024)

Neandertal ancestry through time: Insights from genomes of ancient and present-day humans.

bioRxiv : the preprint server for biology.

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.

RevDate: 2024-05-26
CmpDate: 2024-05-23

Limmer LS, Santon M, McGrath K, et al (2024)

Differences in childhood stress between Neanderthals and early modern humans as reflected by dental enamel growth disruptions.

Scientific reports, 14(1):11293.

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.

RevDate: 2024-06-03
CmpDate: 2024-05-23

Yee SW, Ferrández-Peral L, Alentorn-Moron P, et al (2024)

Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates.

Nature communications, 15(1):4380.

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.

RevDate: 2024-05-24

Gennai J (2024)

The Mousterian in North-Western Tuscany: new data from the Piano di Mommio sites.

Open research Europe, 4:37.

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 region, 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: By enhancing our knowledge of Neanderthal presence in this region through this interdisciplinary approach, this study contributes to a better understanding of the Mousterian culture and the broader narrative of human prehistory in Italy. It underscores the importance of integrating historical field data with modern archaeological techniques to advance our understanding of human history.

RevDate: 2024-05-25
CmpDate: 2024-05-22

Marinelli F, Moncel MH, C Lemorini (2024)

The use of bones as tools in Late Lower Paleolithic of Central Italy.

Scientific reports, 14(1):11666.

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.

RevDate: 2024-05-21
CmpDate: 2024-05-21

Hubáček JA, Šedová L, Hellerová V, et al (2024)

Increased prevalence of the COVID-19 associated Neanderthal mutations in the Central European Roma population.

Annals of human biology, 51(1):2341727.

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.

RevDate: 2024-05-17

Pauly R, Johnson L, Feltus FA, et al (2024)

Enrichment of a subset of Neanderthal polymorphisms in autistic probands and siblings.

Molecular psychiatry [Epub ahead of print].

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.

RevDate: 2024-06-05
CmpDate: 2024-05-13

Helmbrecht N, Lackner M, Maricic T, et al (2024)

The modern human aryl hydrocarbon receptor is more active when ancestralized by genome editing.

Proceedings of the National Academy of Sciences of the United States of America, 121(22):e2402159121.

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.

RevDate: 2024-05-12

Ghasidian E, Kafash A, Kehl M, et al (2024)

Correction: Modelling Neanderthals' dispersal routes from Caucasus towards east.

PloS one, 19(5):e0303722.

[This corrects the article DOI: 10.1371/journal.pone.0281978.].

RevDate: 2024-05-10

Schmidt P, C Tennie (2024)

Problems with two recent Petri net analyses of Neanderthal adhesive technology.

Scientific reports, 14(1):10481.

RevDate: 2024-05-10

Fajardo S, Kozowyk PRB, GHJ Langejans (2024)

Reply to: Problems with two recent Petri net analyses of Neanderthal adhesive technology.

Scientific reports, 14(1):10489.

RevDate: 2024-04-29

Mansueto A, DJ Good (2024)

Conservation of a Chromosome 8 Inversion and Exon Mutations Confirm Common Gulonolactone Oxidase Gene Evolution Among Primates, Including H. Neanderthalensis.

Journal of molecular evolution [Epub ahead of print].

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.

RevDate: 2024-05-23
CmpDate: 2024-04-25

Yousfi FZE, Haroun AE, Nebhani C, et al (2024)

Prevalence of the protective OAS1 rs10774671-G allele against severe COVID-19 in Moroccans: implications for a North African Neanderthal connection.

Archives of virology, 169(5):109.

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.

RevDate: 2024-04-25

Chen S, Tang D, Deng L, et al (2024)

Asian-European differentiation of schizophrenia-associated genes driven by admixture and natural selection.

iScience, 27(5):109560.

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.

RevDate: 2024-04-25
CmpDate: 2024-04-15

Ferreira RC, Rodrigues CR, Broach JR, et al (2024)

Convergent Mutations and Single Nucleotide Variants in Mitochondrial Genomes of Modern Humans and Neanderthals.

International journal of molecular sciences, 25(7):.

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.

RevDate: 2024-05-11
CmpDate: 2024-05-03

Funato N, Heliövaara A, C Boeckx (2024)

A regulatory variant impacting TBX1 expression contributes to basicranial morphology in Homo sapiens.

American journal of human genetics, 111(5):939-953.

Changes in gene regulatory elements play critical roles in human phenotypic divergence. However, identifying the base-pair changes responsible for the distinctive morphology of Homo sapiens remains challenging. Here, we report a noncoding single-nucleotide polymorphism (SNP), rs41298798, as a potential causal variant contributing to the morphology of the skull base and vertebral structures found in Homo sapiens. Screening for differentially regulated genes between Homo sapiens and extinct relatives revealed 13 candidate genes associated with basicranial development, with TBX1, implicated in DiGeorge syndrome, playing a pivotal role. Epigenetic markers and in silico analyses prioritized rs41298798 within a TBX1 intron for functional validation. CRISPR editing revealed that the 41-base-pair region surrounding rs41298798 modulates gene expression at 22q11.21. The derived allele of rs41298798 acts as an allele-specific enhancer mediated by E2F1, resulting in increased TBX1 expression levels compared to the ancestral allele. Tbx1-knockout mice exhibited skull base and vertebral abnormalities similar to those seen in DiGeorge syndrome. Phenotypic differences associated with TBX1 deficiency are observed between Homo sapiens and Neanderthals (Homo neanderthalensis). In conclusion, the regulatory divergence of TBX1 contributes to the formation of skull base and vertebral structures found in Homo sapiens.

RevDate: 2024-04-08
CmpDate: 2024-04-08

Zhao B, Li J, Sinha S, et al (2024)

Pathogenic variants in human DNA damage repair genes mostly arose in recent human history.

BMC cancer, 24(1):415.

BACKGROUND: Genome stability is maintained by the DNA damage repair (DDR) system composed of multiple DNA repair pathways of hundreds of genes. Germline pathogenic variation (PV) in DDR genes damages function of the affected DDR genes, leading to genome instability and high risk of diseases, in particular, cancer. Knowing evolutionary origin of the PVs in human DDR genes is essential to understand the etiology of human diseases. However, answer to the issue remains largely elusive. In this study, we analyzed evolutionary origin for the PVs in human DDR genes.

METHODS: We identified 169 DDR genes by referring to various databases and identified PVs in the DDR genes of modern humans from ClinVar database. We performed a phylogenetic analysis to analyze the conservation of human DDR PVs in 100 vertebrates through cross-species genomic data comparison using the phyloFit program of the PHAST package and visualized the results using the GraphPad Prism software and the ggplot module. We identified DDR PVs from over 5000 ancient humans developed a database to host the DDR PVs ( Using the PV data, we performed a molecular archeological analysis to compare the DDR PVs between modern humans and ancient humans. We analyzed evolution selection of DDR genes across 20 vertebrates using the CodeML in PAML for phylogenetic analysis.

RESULTS: Our phylogenic analysis ruled out cross-species conservation as the origin of human DDR PVs. Our archeological approach identified rich DDR PVs shared between modern and ancient humans, which were mostly dated within the last 5000 years. We also observed similar pattern of quantitative PV distribution between modern and ancient humans. We further detected a set of ATM, BRCA2 and CHEK2 PVs shared between human and Neanderthals.

CONCLUSIONS: Our study reveals that human DDR PVs mostly arose in recent human history. We propose that human high cancer risk caused by DDR PVs can be a by-product of human evolution.

RevDate: 2024-05-06
CmpDate: 2024-04-08

Curry A (2024)

Rare wooden artifacts show the smarts of early Neanderthals.

Science (New York, N.Y.), 384(6691):13-14.

Complex tools from 300,000-year-old deposit at Schöningen in Germany point to a "wood age".

RevDate: 2024-04-05
CmpDate: 2024-04-04

Yaworsky PM, Nielsen ES, TK Nielsen (2024)

The Neanderthal niche space of Western Eurasia 145 ka to 30 ka ago.

Scientific reports, 14(1):7788.

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.

RevDate: 2024-04-01

Aneli S, Ceccatelli Berti C, Gilea AI, et al (2024)

Functional characterization of archaic-specific variants in mitonuclear genes: insights from comparative analysis in S. cerevisiae.

Human molecular genetics pii:7638486 [Epub ahead of print].

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.

RevDate: 2024-05-08
CmpDate: 2024-04-08

Rmoutilová R, Brůžek J, Gómez-Olivencia A, et al (2024)

Sex estimation of the adult Neandertal Regourdou 1 (Montignac, France): Implications for sexing human fossil remains.

Journal of human evolution, 189:103470.

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.

RevDate: 2024-03-27
CmpDate: 2024-03-18

Groh JS, G Coop (2024)

The temporal and genomic scale of selection following hybridization.

Proceedings of the National Academy of Sciences of the United States of America, 121(12):e2309168121.

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.

RevDate: 2024-03-13

Pablos A, JL Arsuaga (2024)

Tarsals from the Sima de los Huesos Middle Pleistocene site (Atapuerca, Burgos, Spain).

Anatomical record (Hoboken, N.J. : 2007) [Epub ahead of print].

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.

RevDate: 2024-03-15
CmpDate: 2024-03-14

Riga A, Profico A, Mori T, et al (2024)

The Middle Pleistocene human metatarsal from Sedia del Diavolo (Rome, Italy).

Scientific reports, 14(1):6024.

The peopling of Europe during the Middle Pleistocene is a debated topic among paleoanthropologists. Some authors suggest the coexistence of multiple human lineages in this period, while others propose a single evolving lineage from Homo heidelbergensis to Homo neanderthalensis. The recent reassessment of the stratigraphy at the Sedia del Diavolo (SdD) site (Latium, Italy), now dated to the beginning of marine isotope stage (MIS) 8, calls for a revision of the human fossils from the site. In this paper, we present the morphometric, biomechanical and palaeopathological study of the second right metatarsal SdD2, to both re-evaluate its taxonomical affinities and possibly determine the levels of physical activity experienced by the individual during lifetime. Results demonstrate the persistence of archaic features in SdD2 suggesting new insights into the technology and hunting strategies adopted by Homo between MIS 9 and MIS 8.

RevDate: 2024-05-08
CmpDate: 2024-04-08

Najafzadeh A, Hernaiz-García M, Benazzi S, et al (2024)

Finite element analysis of Neanderthal and early Homo sapiens maxillary central incisor.

Journal of human evolution, 189:103512.

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.

RevDate: 2024-05-10
CmpDate: 2024-05-10

Geier A, Trost J, Wang K, et al (2024)

PNPLA3 fatty liver allele was fixed in Neanderthals and segregates neutrally in humans.

Gut, 73(6):1008-1014 pii:gutjnl-2023-331594.

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.

RevDate: 2024-03-08

Pantoja-Pérez A, JL Arsuaga (2024)

The Cranium I: Neurocranium.

Anatomical record (Hoboken, N.J. : 2007) [Epub ahead of print].

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.

RevDate: 2024-03-07

Gómez-Olivencia A, JL Arsuaga (2024)

The Sima de los Huesos thorax and lumbar spine: Selected traits and state-of-the-art.

Anatomical record (Hoboken, N.J. : 2007) [Epub ahead of print].

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.

RevDate: 2024-03-04
CmpDate: 2024-03-04

Nowell A (2024)

Knowing the NeanderthalThe Naked Neanderthal: A New Understanding of the Human Creature Ludovic Slimak Pegasus, 2024. 208 pp.

Science (New York, N.Y.), 383(6686):956.

An archaeologist seeks to strip away modern misconceptions about our extinct relatives.

RevDate: 2024-04-12
CmpDate: 2024-04-12

Hernaiz-García M, Zanolli C, Martín-Francés L, et al (2024)

Masticatory habits of the adult Neanderthal individual BD 1 from La Chaise-de-Vouthon (France).

American journal of biological anthropology, 184(1):e24926.

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.

RevDate: 2024-03-11

Kerdoncuff E, Skov L, Patterson N, et al (2024)

50,000 years of Evolutionary History of India: Insights from ~2,700 Whole Genome Sequences.

bioRxiv : the preprint server for biology.

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.

RevDate: 2024-02-24
CmpDate: 2024-02-23

Schmidt P, Iovita R, Charrié-Duhaut A, et al (2024)

Ochre-based compound adhesives at the Mousterian type-site document complex cognition and high investment.

Science advances, 10(8):eadl0822.

Ancient adhesives used in multicomponent tools may be among our best material evidences of cultural evolution and cognitive processes in early humans. African Homo sapiens is known to have made compound adhesives from naturally sticky substances and ochre, a technical behavior proposed to mark the advent of elaborate cognitive processes in our species. Foragers of the European Middle Paleolithic also used glues, but evidence of ochre-based compound adhesives is unknown. Here, we present evidence of this kind. Bitumen was mixed with high loads of goethite ochre to make compound adhesives at the type-site of the Mousterian, Le Moustier (France). Ochre loads were so high that they lowered the adhesive's performance in classical hafting situations where stone implements are glued to handles. However, when used as handheld grips on cutting or scraping tools, a behavior known from Neanderthals, high-ochre adhesives present a real benefit, improving their solidity and rigidity. Our findings help understand the implications of Pleistocene adhesive making.

RevDate: 2024-02-21

Pablos A, JL Arsuaga (2024)

Metatarsals and foot phalanges from the Sima de los Huesos Middle Pleistocene site (Atapuerca, Burgos, Spain).

Anatomical record (Hoboken, N.J. : 2007) [Epub ahead of print].

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.

RevDate: 2024-02-23

Cerrito P, Nava A, Radovčić D, et al (2024)

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 of the Royal Society, Interface, 21(211):20240069.

RevDate: 2024-03-31
CmpDate: 2024-03-28

Liu S, Luo H, Zhang P, et al (2024)

Adaptive Selection of Cis-regulatory Elements in the Han Chinese.

Molecular biology and evolution, 41(3):.

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.

RevDate: 2024-02-20

Yousefi M, Jouladeh-Roudbar A, A Kafash (2024)

Mapping endemic freshwater fish richness to identify high-priority areas for conservation: An ecoregion approach.

Ecology and evolution, 14(2):e10970.

Freshwater ecosystems are experiencing accelerating global biodiversity loss. Thus, knowing where these unique ecosystems' species richness reaches a peak can facilitate their conservation planning. By hosting more than 290 freshwater fishes, Iran is a major freshwater fish hotspot in the Middle East. Considering the accelerating rate of biodiversity loss, there is an urgent need to identify species-rich areas and understand the mechanisms driving biodiversity distribution. In this study, we gathered distribution records of all endemic freshwater fishes of Iran (85 species) to develop their richness map and determine the most critical drivers of their richness patterns from an ecoregion approach. We performed a generalized linear model (GLM) with quasi-Poisson distribution to identify contemporary and historical determinants of endemic freshwater fish richness. We also quantified endemic fish similarity among the 15 freshwater ecoregions of Iran. Results showed that endemic freshwater fish richness is highest in the Zagros Mountains while a moderate level of richness was observed between Zagros and Alborz Mountains. High, moderate, and low richness of endemic freshwater fish match with Upper Tigris & Euphrates, Namak, and Kavir & Lut Deserts ecoregions respectively. Kura - South Caspian Drainages and Caspian Highlands were the most similar ecoregions and Orumiyeh was the most unique ecoregion according to endemic fish presence. Precipitation and precipitation change velocity since the Last Glacial Maximum were the most important predictors of endemic freshwater fish richness. Areas identified to have the highest species richness have high priority for the conservation of freshwater fish in Iran, therefore, should be considered in future protected areas development.

RevDate: 2024-02-20
CmpDate: 2024-02-20

Dehay C, WB Huttner (2024)

Development and evolution of the primate neocortex from a progenitor cell perspective.

Development (Cambridge, England), 151(4):.

The generation of neurons in the developing neocortex is a major determinant of neocortex size. Crucially, the increase in cortical neuron numbers in the primate lineage, notably in the upper-layer neurons, contributes to increased cognitive abilities. Here, we review major evolutionary changes affecting the apical progenitors in the ventricular zone and focus on the key germinal zone constituting the foundation of neocortical neurogenesis in primates, the outer subventricular zone (OSVZ). We summarize characteristic features of the OSVZ and its key stem cell type, the basal (or outer) radial glia. Next, we concentrate on primate-specific and human-specific genes, expressed in OSVZ-progenitors, the ability of which to amplify these progenitors by targeting the regulation of the cell cycle ultimately underlies the evolutionary increase in upper-layer neurons. Finally, we address likely differences in neocortical development between present-day humans and Neanderthals that are based on human-specific amino acid substitutions in proteins operating in cortical progenitors.

RevDate: 2024-03-25
CmpDate: 2024-03-25

Voinescu CD, Mozere M, Genovese G, et al (2024)

A Neanderthal haplotype introgressed into the human genome confers protection against membranous nephropathy.

Kidney international, 105(4):791-798.

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.

RevDate: 2024-03-08
CmpDate: 2024-03-04

Zeberg H, Jakobsson M, S Pääbo (2024)

The genetic changes that shaped Neandertals, Denisovans, and modern humans.

Cell, 187(5):1047-1058.

Modern human ancestors diverged from the ancestors of Neandertals and Denisovans about 600,000 years ago. Until about 40,000 years ago, these three groups existed in parallel, occasionally met, and exchanged genes. A critical question is why modern humans, and not the other two groups, survived, became numerous, and developed complex cultures. Here, we discuss genetic differences among the groups and some of their functional consequences. As more present-day genome sequences become available from diverse groups, we predict that very few, if any, differences will distinguish all modern humans from all Neandertals and Denisovans. We propose that the genetic basis of what constitutes a modern human is best thought of as a combination of genetic features, where perhaps none of them is present in each and every present-day individual.

RevDate: 2024-02-12

Yaghmouri M, P Izadi (2024)

Role of the Neanderthal Genome in Genetic Susceptibility to COVID-19: 3p21.31 Locus in the Spotlight.

Biochemical genetics [Epub ahead of print].

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.

RevDate: 2024-02-05

Russo G, Milks A, Leder D, et al (2024)

Author Correction: First direct evidence of lion hunting and the early use of a lion pelt by Neanderthals.

Scientific reports, 14(1):2772 pii:10.1038/s41598-024-52963-y.

RevDate: 2024-02-08
CmpDate: 2024-02-08

Curry A (2024)

In Europe, an early, cold dawn for modern humans.

Science (New York, N.Y.), 383(6682):468-469.

Moderns made mysterious ice age artifacts-implying overlap with Neanderthals.

RevDate: 2024-03-21
CmpDate: 2024-03-13

Pederzani S, Britton K, Trost M, et al (2024)

Stable isotopes show Homo sapiens dispersed into cold steppes ~45,000 years ago at Ilsenhöhle in Ranis, Germany.

Nature ecology & evolution, 8(3):578-588.

The spread of Homo sapiens into new habitats across Eurasia ~45,000 years ago and the concurrent disappearance of Neanderthals represents a critical evolutionary turnover in our species' history. 'Transitional' technocomplexes, such as the Lincombian-Ranisian-Jerzmanowician (LRJ), characterize the European record during this period but their makers and evolutionary significance have long remained unclear. New evidence from Ilsenhöhle in Ranis, Germany, now provides a secure connection of the LRJ to H. sapiens remains dated to ~45,000 years ago, making it one of the earliest forays of our species to central Europe. Using many stable isotope records of climate produced from 16 serially sampled equid teeth spanning ~12,500 years of LRJ and Upper Palaeolithic human occupation at Ranis, we review the ability of early humans to adapt to different climate and habitat conditions. Results show that cold climates prevailed across LRJ occupations, with a temperature decrease culminating in a pronounced cold excursion at ~45,000-43,000 cal BP. Directly dated H. sapiens remains confirm that humans used the site even during this very cold phase. Together with recent evidence from the Initial Upper Palaeolithic, this demonstrates that humans operated in severe cold conditions during many distinct early dispersals into Europe and suggests pronounced adaptability.

RevDate: 2024-03-13
CmpDate: 2024-02-15

Mylopotamitaki D, Weiss M, Fewlass H, et al (2024)

Homo sapiens reached the higher latitudes of Europe by 45,000 years ago.

Nature, 626(7998):341-346.

The Middle to Upper Palaeolithic transition in Europe is associated with the regional disappearance of Neanderthals and the spread of Homo sapiens. Late Neanderthals persisted in western Europe several millennia after the occurrence of H. sapiens in eastern Europe[1]. Local hybridization between the two groups occurred[2], but not on all occasions[3]. Archaeological evidence also indicates the presence of several technocomplexes during this transition, complicating our understanding and the association of behavioural adaptations with specific hominin groups[4]. One such technocomplex for which the makers are unknown is the Lincombian-Ranisian-Jerzmanowician (LRJ), which has been described in northwestern and central Europe[5-8]. Here we present the morphological and proteomic taxonomic identification, mitochondrial DNA analysis and direct radiocarbon dating of human remains directly associated with an LRJ assemblage at the site Ilsenhöhle in Ranis (Germany). These human remains are among the earliest directly dated Upper Palaeolithic H. sapiens remains in Eurasia. We show that early H. sapiens associated with the LRJ were present in central and northwestern Europe long before the extinction of late Neanderthals in southwestern Europe. Our results strengthen the notion of a patchwork of distinct human populations and technocomplexes present in Europe during this transitional period.

RevDate: 2024-02-05

Janivara R, Hazra U, Pfennig A, et al (2024)

Uncovering the genetic architecture and evolutionary roots of androgenetic alopecia in African men.

bioRxiv : the preprint server for biology.

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.

RevDate: 2024-01-26

Jambrina-Enríquez M, Mallol C, Herrera Herrera AV, et al (2024)

Microstratigraphic, lipid biomarker and stable isotope study of a middle Palaeolithic combustion feature from Axlor, Spain.

iScience, 27(1):108755.

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.

RevDate: 2024-05-08
CmpDate: 2024-02-14

Bailey SE, Davies TW, Imbrasas MD, et al (2024)

New Neanderthal remains from Axlor cave (Dima, Biscay, northern Iberian Peninsula).

Journal of human evolution, 187:103483.

RevDate: 2024-01-28

Massé L, d'Incau E, Souron A, et al (2024)

Unraveling the Life History of Past Populations through Hypercementosis: Insights into Cementum Apposition Patterns and Possible Etiologies Using Micro-CT and Confocal Microscopy.

Biology, 13(1):.

The "teeth-as-tools" hypothesis posits that Neanderthals used their anterior teeth as a tool or a third hand for non-dietary purposes. These non- or para-masticatory activities (e.g., tool-making or food preparation prior to ingestion) have also been described in other past and extant human populations, and other Primates. Cementum is the mineralized tissue that covers the tooth root surface and anchors it to the alveolar bone. Under certain conditions (e.g., mechanical stress, infection), its production becomes excessive (i.e., beyond the physiological state) and is called 'hypercementosis'. Several studies in dental anthropology have established a correlation between the teeth-as-tools and hypercementosis. The present work aims to characterize the different patterns of cementum apposition on archeological teeth and discuss their supposed etiology. Using microtomography and confocal microscopy, the patterns of cementum apposition (i.e., thickness, location, and surface characteristics) were analyzed in 35 hypercementotic teeth (Sains-en-Gohelle, France; 7th-17th c. A.D.). Four groups were identified with distinct hypercementosis patterns: (1) impacted, (2) infected, (3) hypofunctional, and (4) hyperfunctional teeth. Characterizing hypercementosis can contribute to documenting the oral health status (paleopathology) and/or masticatory activity of individuals, even from isolated teeth. This has implications for the study of fossil hominins, particularly Neanderthals, known for their use of anterior teeth as tools and frequent and substantial occurrence of hypercementosis.

RevDate: 2024-01-12

Borodko DD, Zhenilo SV, FS Sharko (2023)

Search for differentially methylated regions in ancient and modern genomes.

Vavilovskii zhurnal genetiki i selektsii, 27(7):820-828.

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.

RevDate: 2024-04-26
CmpDate: 2024-02-22

Huttner WB, Heide M, Mora-Bermúdez F, et al (2024)

Neocortical neurogenesis in development and evolution-Human-specific features.

The Journal of comparative neurology, 532(2):e25576.

In this review, we focus on human-specific features of neocortical neurogenesis in development and evolution. Two distinct topics will be addressed. In the first section, we discuss the expansion of the neocortex during human evolution and concentrate on the human-specific gene ARHGAP11B. We review the ability of ARHGAP11B to amplify basal progenitors and to expand a primate neocortex. We discuss the contribution of ARHGAP11B to neocortex expansion during human evolution and its potential implications for neurodevelopmental disorders and brain tumors. We then review the action of ARHGAP11B in mitochondria as a regulator of basal progenitor metabolism, and how it promotes glutaminolysis and basal progenitor proliferation. Finally, we discuss the increase in cognitive performance due to the ARHGAP11B-induced neocortical expansion. In the second section, we focus on neocortical development in modern humans versus Neanderthals. Specifically, we discuss two recent findings pointing to differences in neocortical neurogenesis between these two hominins that are due to a small number of amino acid substitutions in certain key proteins. One set of such proteins are the kinetochore-associated proteins KIF18a and KNL1, where three modern human-specific amino acid substitutions underlie the prolongation of metaphase during apical progenitor mitosis. This prolongation in turn is associated with an increased fidelity of chromosome segregation to the apical progenitor progeny during modern human neocortical development, with implications for the proper formation of radial units. Another such key protein is transketolase-like 1 (TKTL1), where a single modern human-specific amino acid substitution endows TKTL1 with the ability to amplify basal radial glia, resulting in an increase in upper-layer neuron generation. TKTL1's ability is based on its action in the pentose phosphate pathway, resulting in increased fatty acid synthesis. The data imply greater neurogenesis during neocortical development in modern humans than Neanderthals due to TKTL1, in particular in the developing frontal lobe.

RevDate: 2024-01-08
CmpDate: 2024-01-05

Levinstein Hallak K, S Rosset (2024)

Dating ancient splits in phylogenetic trees, with application to the human-Neanderthal split.

BMC genomic data, 25(1):4.

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.

RevDate: 2024-05-08
CmpDate: 2024-02-14

Palancar CA, Bastir M, Rosas A, et al (2024)

Modern human atlas ranges of motion and Neanderthal estimations.

Journal of human evolution, 187:103482.

RevDate: 2024-04-10
CmpDate: 2024-04-08

Zhao H, Liu LL, Sun J, et al (2024)

A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression.

Science China. Life sciences, 67(4):765-777.

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.

RevDate: 2024-01-31
CmpDate: 2023-12-16

Velazquez-Arcelay K, Colbran LL, McArthur E, et al (2023)

Archaic Introgression Shaped Human Circadian Traits.

Genome biology and evolution, 15(12):.

When the ancestors of modern Eurasians migrated out of Africa and interbred with Eurasian archaic hominins, namely, Neanderthals and Denisovans, DNA of archaic ancestry integrated into the genomes of anatomically modern humans. This process potentially accelerated adaptation to Eurasian environmental factors, including reduced ultraviolet radiation and increased variation in seasonal dynamics. However, whether these groups differed substantially in circadian biology and whether archaic introgression adaptively contributed to human chronotypes remain unknown. Here, we traced the evolution of chronotype based on genomes from archaic hominins and present-day humans. First, we inferred differences in circadian gene sequences, splicing, and regulation between archaic hominins and modern humans. We identified 28 circadian genes containing variants with potential to alter splicing in archaics (e.g., CLOCK, PER2, RORB, and RORC) and 16 circadian genes likely divergently regulated between present-day humans and archaic hominins, including RORA. These differences suggest the potential for introgression to modify circadian gene expression. Testing this hypothesis, we found that introgressed variants are enriched among expression quantitative trait loci for circadian genes. Supporting the functional relevance of these regulatory effects, we found that many introgressed alleles have associations with chronotype. Strikingly, the strongest introgressed effects on chronotype increase morningness, consistent with adaptations to high latitude in other species. Finally, we identified several circadian loci with evidence of adaptive introgression or latitudinal clines in allele frequency. These findings identify differences in circadian gene regulation between modern humans and archaic hominins and support the contribution of introgression via coordinated effects on variation in human chronotype.

RevDate: 2024-05-06
CmpDate: 2024-05-06

Hui J, A Balzeau (2024)

Investigating the relationship between cranial bone thickness and diploic channels: A first comparison between fossil Homo sapiens and Homo neanderthalensis.

Anatomical record (Hoboken, N.J. : 2007), 307(6):2036-2046.

Diploic veins are part of the circulatory system of the head. They transport venous blood and cerebrospinal fluid and are housed in diploic channels (DCs). DCs are highly variable in terms of their position, extension, and size. These parameters were hypothesized to be related to the variations in cranial vault thickness (CVT). For the first time, we analyzed the spatial relationship between CVT and DCs in a sample of eight H. neanderthalensis and H. sapiens cranial fossils. Using micro-CT scanning data, we constructed color maps of the CVT and visually inspected whether the regional thickness variation was associated with the morphology and distribution of the DC branches. The results showed that when regional bone thickness was below a certain threshold, no DCs or scattered small DC branches were present. Larger DC branches appeared only when the thickness exceeded the threshold. However, once the threshold was reached, further increases in thickness no longer resulted in more or larger DCs. This study also found that our sample of H. neanderthalensis and H. sapiens have different distribution patterns in thin areas, which may affect how their DCs connect with different branches of the middle meningeal vessels. This preliminary study provides evidence for the discussion on the interaction between the cranium, brain, and blood vessels. Future research should include more hominin fossils to better document the variation within each species and possible evolutionary trends among hominin lineages.

RevDate: 2024-01-31
CmpDate: 2023-12-20

Wroblewski TH, Witt KE, Lee SB, et al (2023)

Pharmacogenetic Variation in Neanderthals and Denisovans and Implications for Human Health and Response to Medications.

Genome biology and evolution, 15(12):.

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.

RevDate: 2023-12-17
CmpDate: 2023-12-06

Gaudzinski-Windheuser S, Kindler L, W Roebroeks (2023)

Widespread evidence for elephant exploitation by Last Interglacial Neanderthals on the North European plain.

Proceedings of the National Academy of Sciences of the United States of America, 120(50):e2309427120.

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.

RevDate: 2024-05-08
CmpDate: 2024-01-01

Abrams G, Devièse T, Pirson S, et al (2024)

Investigating the co-occurrence of Neanderthals and modern humans in Belgium through direct radiocarbon dating of bone implements.

Journal of human evolution, 186:103471.

RevDate: 2023-12-01

Agata A, Ohtsuka S, Noji R, et al (2023)

A Neanderthal/Denisovan GLI3 variant contributes to anatomical variations in mice.

Frontiers in cell and developmental biology, 11:1247361.

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.

RevDate: 2024-03-28
CmpDate: 2023-11-29

Lee OY, Wu HHT, Besra GS, et al (2023)

Sensitive lipid biomarker detection for tuberculosis in late Neanderthal skeletons from Subalyuk Cave, Hungary.

Tuberculosis (Edinburgh, Scotland), 143S:102420.

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.

RevDate: 2024-03-28
CmpDate: 2023-11-29

Pálfi G, Molnár E, Bereczki Z, et al (2023)

Re-examination of the Subalyuk Neanderthal remains uncovers signs of probable TB infection (Subalyuk Cave, Hungary).

Tuberculosis (Edinburgh, Scotland), 143S:102419.

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].

RevDate: 2023-12-16
CmpDate: 2023-12-16

Di Santo LN, Quilodrán CS, M Currat (2023)

Temporal Variation in Introgressed Segments' Length Statistics Computed from a Limited Number of Ancient Genomes Sheds Light on Past Admixture Pulses.

Molecular biology and evolution, 40(12):.

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.

RevDate: 2024-02-07
CmpDate: 2023-11-27

Ragsdale AP (2023)

Human evolution: Neanderthal footprints in African genomes.

Current biology : CB, 33(22):R1197-R1200.

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.

RevDate: 2023-12-22
CmpDate: 2023-12-22

Urnikyte A, Masiulyte A, Pranckeniene L, et al (2023)

Disentangling archaic introgression and genomic signatures of selection at human immunity genes.

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 116:105528.

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.

RevDate: 2024-01-12
CmpDate: 2024-01-12

Raja A, JJW Kuiper (2023)

Evolutionary immuno-genetics of endoplasmic reticulum aminopeptidase II (ERAP2).

Genes and immunity, 24(6):295-302.

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.

RevDate: 2024-05-08
CmpDate: 2023-11-27

López-Rey JM, García-Martínez D, Martelli S, et al (2023)

Estimation of the upper diaphragm in KNM-WT 15000 (Homo erectus s.l.) and Kebara 2 (Homo neanderthalensis) using a Homo sapiens model.

Journal of human evolution, 185:103442.

RevDate: 2023-11-30
CmpDate: 2023-11-30

Quilodrán CS, Rio J, Tsoupas A, et al (2023)

Past human expansions shaped the spatial pattern of Neanderthal ancestry.

Science advances, 9(42):eadg9817.

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.

RevDate: 2024-02-21
CmpDate: 2024-02-14

Chen Y, Yu XY, Xu SJ, et al (2024)

An indel introduced by Neanderthal introgression, rs3835124:ATTTATT > ATT, might contribute to prostate cancer risk by regulating PDK1 expression.

Annals of human genetics, 88(2):126-137.

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.

RevDate: 2024-02-07
CmpDate: 2023-11-27

Harris DN, Platt A, Hansen MEB, et al (2023)

Diverse African genomes reveal selection on ancient modern human introgressions in Neanderthals.

Current biology : CB, 33(22):4905-4916.e5.

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.

RevDate: 2024-02-04
CmpDate: 2023-11-01

Russo G, Milks A, Leder D, et al (2023)

First direct evidence of lion hunting and the early use of a lion pelt by Neanderthals.

Scientific reports, 13(1):16405.

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.

RevDate: 2023-11-02
CmpDate: 2023-11-01

Angelucci DE, Nabais M, J Zilhão (2023)

Formation processes, fire use, and patterns of human occupation across the Middle Palaeolithic (MIS 5a-5b) of Gruta da Oliveira (Almonda karst system, Torres Novas, Portugal).

PloS one, 18(10):e0292075.

Gruta da Oliveira features a c. 13 m-thick infilling that includes a c. 6.5 m-thick archaeological deposit (the "Middle Palaeolithic sequence" complex), which Bayesian modelling of available dating results places in MIS 5a (layers 7-14) and MIS 5b (layers 15-25), c. 71,000-93,000 years ago. The accumulation primarily consists of sediment washed in from the slope through gravitational processes and surface dynamics. The coarse fraction derives from weathering of the cave's limestone bedrock. Tectonic activity and structural instability caused the erosional retreat of the scarp face, explaining the large, roof-collapsed rock masses found through the stratification. The changes in deposition and diagenesis observed across the archaeological sequence are minor and primarily controlled by local factors and the impact of humans and other biological agents. Pulses of stadial accumulation-reflected in the composition of the assemblages of hunted ungulates, mostly open-country and rocky terrain taxa (rhino, horse, ibex)-alternate with interstadial hiatuses-during which carbonate crusts and flowstone formed. Humans were active at the cave throughout, but occupation was intermittent, which allowed for limited usage by carnivores when people visited less frequently. During the accumulation of layers 15-25 (c. 85,000-93,000 years ago), the carnivore guild was dominated by wolf and lion, while brown bear and lynx predominate in layers 7-14 (c. 71,000-78,000 years ago). In the excavated areas, conditions for residential use were optimal during the accumulation of layers 20-22 (c. 90,000-92,000 years ago) and 14 (c. 76,000-78,000 years ago), which yielded dense, hearth-focused scatters of stone tools and burnt bones. The latter are ubiquitous, adding to the growing body of evidence that Middle Palaeolithic Neandertals used fire in regular, consistent manner. The patterns of site usage revealed at Gruta da Oliveira are no different from those observed 50,000 years later in comparable early Upper Palaeolithic and Solutrean cave sites of central Portugal.

RevDate: 2024-03-06
CmpDate: 2023-11-01

Faux P, Ding L, Ramirez-Aristeguieta LM, et al (2023)

Neanderthal introgression in SCN9A impacts mechanical pain sensitivity.

Communications biology, 6(1):958.

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.

RevDate: 2024-02-10

Villanea FA, Peede D, Kaufman EJ, et al (2023)

The MUC19 gene in Denisovans, Neanderthals, and Modern Humans: An Evolutionary History of Recurrent Introgression and Natural Selection.

bioRxiv : the preprint server for biology.

All humans carry a small fraction of archaic ancestry across the genome, the legacy of gene flow from Neanderthals, Denisovans, and other hominids into the ancestors of modern humans. While the effects of Neanderthal ancestry on human fitness and health have been explored more thoroughly, there are fewer examples of adaptive introgression of Denisovan variants. Here, we study the gene MUC19, for which some modern humans carry a Denisovan-like haplotype. MUC19 is a mucin, a glycoprotein that forms gels with various biological functions, from lubrication to immunity. We find the diagnostic variants for the Denisovan-like MUC19 haplotype at high frequencies in admixed Latin American individuals among global population, and at highest frequency in 23 ancient Indigenous American individuals, all predating population admixture with Europeans and Africans. We find that some Neanderthals--Vindija and Chagyrskaya--carry the Denisovan-like MUC19 haplotype, and that it was likely introgressed into human populations through Neanderthal introgression rather than Denisovan introgression. Finally, we find that the Denisovan-like MUC19 haplotype carries a higher copy number of a 30 base-pair variable number tandem repeat relative to the Human-like haplotype, and that copy numbers of this repeat are exceedingly high in American populations. Our results suggest that the Denisovan-like MUC19 haplotype served as the raw genetic material for positive selection as American populations adapted to novel environments during their movement from Beringia into North and then South America.

RevDate: 2023-10-05

Carretero JM, Rodríguez L, García-González R, et al (2023)

Main morphological characteristics and sexual dimorphism of hominin adult femora from the Sima de los Huesos Middle Pleistocene site (Sierra de Atapuerca, Spain).

Anatomical record (Hoboken, N.J. : 2007) [Epub ahead of print].

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.

RevDate: 2023-10-04

Rodríguez L, García-González R, Arsuaga JL, et al (2023)

Exploring the morphology of adult tibia and fibula from Sima de los Huesos site in sierra de Atapuerca, Burgos, Spain.

Anatomical record (Hoboken, N.J. : 2007) [Epub ahead of print].

The analysis of the locomotor anatomy of Late Pleistocene Homo has largely focused on changes in proximal femur and pelvic morphologies, with much attention centered on the emergence of modern humans. Although much of the focus has been on changes in the proximal femur, some research has also been conducted on tibiae and, to a lesser extent, fibulae. With this in mind, we present one of the largest samples of the same population of human tibiae and fibulae from the Middle Pleistocene to determine their main characteristic traits and establish similarities and differences, primarily with those of Neanderthals and modern humans, but also with other Middle Pleistocene specimens in the fossil record. Through this study, we established that the Middle Pleistocene population from the Sima de los Huesos (Atapuerca, Burgos, Spain) had lower leg long bones similar to those of Neanderthals, although there were some important differences, such as bone length, which this fossil individuals resembled those of modern humans and not to Neanderthals. This fact is related to the crural index and leg length, even though we do not have any true association between femora and tibiae yet, it has implications for establishing locomotor efficiency and climate adaptation.

RevDate: 2024-06-03

Yee SW, Ferrández-Peral L, Alentorn P, et al (2023)

Illuminating the Function of the Orphan Transporter, SLC22A10 in Humans and Other Primates.

Research square.

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.

RevDate: 2023-10-31
CmpDate: 2023-10-31

Zhang Y, Z Li (2023)

Investigating the internal structure of the suprainiac fossa in Xuchang 2.

Journal of human evolution, 184:103440.

RevDate: 2023-10-14

Hui J, A Balzeau (2023)

The diploic venous system in Homo neanderthalensis and fossil Homo sapiens: A study using high-resolution computed tomography.

American journal of biological anthropology, 182(3):412-427.

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.

RevDate: 2023-10-19
CmpDate: 2023-09-25

Vidal-Cordasco M, Terlato G, Ocio D, et al (2023)

Neanderthal coexistence with Homo sapiens in Europe was affected by herbivore carrying capacity.

Science advances, 9(38):eadi4099.

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.

RevDate: 2024-05-09
CmpDate: 2023-09-25

Fajardo S, Kozowyk PRB, GHJ Langejans (2023)

Measuring ancient technological complexity and its cognitive implications using Petri nets.

Scientific reports, 13(1):14961.

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.

RevDate: 2023-09-22

Breno M, Noris M, Rubis N, et al (2023)

A GWAS in the pandemic epicenter highlights the severe COVID-19 risk locus introgressed by Neanderthals.

iScience, 26(10):107629.

Large GWAS indicated that genetic factors influence the response to SARS-CoV-2. However, sex, age, concomitant diseases, differences in ancestry, and uneven exposure to the virus impacted the interpretation of data. We aimed to perform a GWAS of COVID-19 outcome in a homogeneous population who experienced a high exposure to the virus and with a known infection status. We recruited inhabitants of Bergamo province-that in spring 2020 was the epicenter of the SARS-Cov-2 pandemic in Europe-via an online questionnaire followed by personal interviews. Cases and controls were matched by age, sex and risk factors. We genotyped 1195 individuals and replicated the association at the 3p21.31 locus with severity, but with a stronger effect size that further increased in gravely ill patients. Transcriptome-wide association study highlighted eQTLs for LZTFL1 and CCR9. We also identified 17 loci not previously reported, suggestive for an association with either COVID-19 severity or susceptibility.

RevDate: 2024-02-01
CmpDate: 2024-01-24

Peyrégne S, Slon V, J Kelso (2024)

More than a decade of genetic research on the Denisovans.

Nature reviews. Genetics, 25(2):83-103.

Denisovans, a group of now extinct humans who lived in Eastern Eurasia in the Middle and Late Pleistocene, were first identified from DNA sequences just over a decade ago. Only ten fragmentary remains from two sites have been attributed to Denisovans based entirely on molecular information. Nevertheless, there has been great interest in using genetic data to understand Denisovans and their place in human history. From the reconstruction of a single high-quality genome, it has been possible to infer their population history, including events of admixture with other human groups. Additionally, the identification of Denisovan DNA in the genomes of present-day individuals has provided insights into the timing and routes of dispersal of ancient modern humans into Asia and Oceania, as well as the contributions of archaic DNA to the physiology of present-day people. In this Review, we synthesize more than a decade of research on Denisovans, reconcile controversies and summarize insights into their population history and phenotype. We also highlight how our growing knowledge about Denisovans has provided insights into our own evolutionary history.

RevDate: 2023-11-02
CmpDate: 2023-11-02

Ge X, Lu Y, Chen S, et al (2023)

Genetic Origins and Adaptive Evolution of the Deng People on the Tibetan Plateau.

Molecular biology and evolution, 40(10):.

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.

RevDate: 2023-11-18
CmpDate: 2023-09-11

Kozowyk PRB, Baron LI, GHJ Langejans (2023)

Identifying Palaeolithic birch tar production techniques: challenges from an experimental biomolecular approach.

Scientific reports, 13(1):14727.

The intentional production of birch bark tar by European Neanderthals as early as 190,000 years ago plays an important role in discussions about the technological and behavioural complexity of Pleistocene hominins. However, research is hampered because it is currently unknown how Neanderthals were producing birch tar. There are several different techniques that could have been employed, but these differ in their apparent production complexity, time and resource efficiency. Identifying production processes in the archaeological record is therefore paramount for furthering research on the technical behavioural repertoire. Organic biomarkers, identified with Gas Chromatograph-Mass Spectrometry (GC-MS), have been used to identify possible production processes during the Neolithic. Here we test whether these biomarkers can also distinguish Palaeolithic (aceramic) tar production methods. We produced tar using five different methods and analysed their biomolecular composition with GC-MS. Our results show that the biomarkers used to distinguish Neolithic tar production strategies using ceramic technology cannot be reliably used to identify tar production processes using aceramic Palaeolithic techniques. More experimentation is required to produce a larger reference library of different tars for future comparisons. To achieve this, complete GC-MS datasets must also be made publicly available, as we have done with our data.

RevDate: 2024-05-09
CmpDate: 2023-09-11

Kozowyk PRB, Fajardo S, GHJ Langejans (2023)

Scaling Palaeolithic tar production processes exponentially increases behavioural complexity.

Scientific reports, 13(1):14709.

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.

RevDate: 2023-09-30
CmpDate: 2023-09-29

Flegontov P, Işıldak U, Maier R, et al (2023)

Modeling of African population history using f-statistics is biased when applying all previously proposed SNP ascertainment schemes.

PLoS genetics, 19(9):e1010931.

f-statistics have emerged as a first line of analysis for making inferences about demographic history from genome-wide data. Not only are they guaranteed to allow robust tests of the fits of proposed models of population history to data when analyzing full genome sequencing data-that is, all single nucleotide polymorphisms (SNPs) in the individuals being analyzed-but they are also guaranteed to allow robust tests of models for SNPs ascertained as polymorphic in a population that is an outgroup in a phylogenetic sense to all groups being analyzed. True "outgroup ascertainment" is in practice impossible in humans because our species has arisen from a substructured ancestral population that does not descend from a homogeneous ancestral population going back many hundreds of thousands of years into the past. However, initial studies suggested that non-outgroup-ascertainment schemes might produce robust enough results using f-statistics, and that motivated widespread fitting of models to data using non-outgroup-ascertained SNP panels such as the "Affymetrix Human Origins array" which has been genotyped on thousands of modern individuals from hundreds of populations, or the "1240k" in-solution enrichment reagent which has been the source of about 70% of published genome-wide data for ancient humans. In this study, we show that while analyses of population history using such panels work well for studies of relationships among non-African populations and one African outgroup, when co-modeling more than one sub-Saharan African and/or archaic human groups (Neanderthals and Denisovans), fitting of f-statistics to such SNP sets is expected to frequently lead to false rejection of true demographic histories, and failure to reject incorrect models. Analyzing panels of SNPs polymorphic in archaic humans, which has been suggested as a solution for the ascertainment problem, has limited statistical power and retains important biases. However, by carrying out simulations of diverse demographic histories, we show that bias in inferences based on f-statistics can be minimized by ascertaining on variants common in a union of diverse African groups; such ascertainment retains high statistical power while allowing co-analysis of archaic and modern groups.

RevDate: 2024-03-06
CmpDate: 2024-03-06

Mester Z, Coqueugniot H, Tillier AM, et al (2024)

First direct dating of the Late Neanderthal remains from Subalyuk Cave in Northern Hungary.

Anthropologischer Anzeiger; Bericht uber die biologisch-anthropologische Literatur, 81(2):169-181.

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.

RevDate: 2023-11-18
CmpDate: 2023-09-04

Glunčić M, Vlahović I, Rosandić M, et al (2023)

Tandem NBPF 3mer HORs (Olduvai triplets) in Neanderthal and two novel HOR tandem arrays in human chromosome 1 T2T-CHM13 assembly.

Scientific reports, 13(1):14420.

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.

RevDate: 2023-10-25
CmpDate: 2023-10-23

Fiorenza L, Habashi W, Moggi-Cecchi J, et al (2023)

Relationship between interproximal and occlusal wear in Australopithecus africanus and Neanderthal molars.

Journal of human evolution, 183:103423.

RevDate: 2024-06-03

Yee SW, Ferrández-Peral L, Alentorn P, et al (2023)

Illuminating the Function of the Orphan Transporter, SLC22A10 in Humans and Other Primates.

bioRxiv : the preprint server for biology.

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.

RevDate: 2023-09-30
CmpDate: 2023-09-15

Chevy ET, Huerta-Sánchez E, S Ramachandran (2023)

Integrating sex-bias into studies of archaic introgression on chromosome X.

PLoS genetics, 19(8):e1010399.

Evidence of interbreeding between archaic hominins and humans comes from methods that infer the locations of segments of archaic haplotypes, or 'archaic coverage' using the genomes of people living today. As more estimates of archaic coverage have emerged, it has become clear that most of this coverage is found on the autosomes- very little is retained on chromosome X. Here, we summarize published estimates of archaic coverage on autosomes and chromosome X from extant human samples. We find on average 7 times more archaic coverage on autosomes than chromosome X, and identify broad continental patterns in this ratio: greatest in European samples, and least in South Asian samples. We also perform extensive simulation studies to investigate how the amount of archaic coverage, lengths of coverage, and rates of purging of archaic coverage are affected by sex-bias caused by an unequal sex ratio within the archaic introgressors. Our results generally confirm that, with increasing male sex-bias, less archaic coverage is retained on chromosome X. Ours is the first study to explicitly model such sex-bias and its potential role in creating the dearth of archaic coverage on chromosome X.

RevDate: 2024-03-13
CmpDate: 2023-08-16

Piccardi M, Gentiluomo M, Bertoncini S, et al (2023)

Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians.

Biological research, 56(1):46.

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.

RevDate: 2023-09-22
CmpDate: 2023-08-14

Ruan J, Timmermann A, Raia P, et al (2023)

Climate shifts orchestrated hominin interbreeding events across Eurasia.

Science (New York, N.Y.), 381(6658):699-704.

When, where, and how often hominin interbreeding happened is largely unknown. We study the potential for Neanderthal-Denisovan admixture using species distribution models that integrate extensive fossil, archaeological, and genetic data with transient coupled general circulation model simulations of global climate and biomes. Our Pleistocene hindcast of past hominins' habitat suitability reveals pronounced climate-driven zonal shifts in the main overlap region of Denisovans and Neanderthals in central Eurasia. These shifts, which influenced the timing and intensity of potential interbreeding events, can be attributed to the response of climate and vegetation to past variations in atmospheric carbon dioxide and Northern Hemisphere ice-sheet volume. Therefore, glacial-interglacial climate swings likely played an important role in favoring gene flow between archaic humans.

RevDate: 2023-10-21

Garralda MD, Le Cabec A, Maíllo Fernández JM, et al (2023)

Mousterian human fossils from El Castillo cave (Puente Viesgo, Cantabria, Spain).

Journal of anthropological sciences = Rivista di antropologia : JASS, 100:123-142.

El Castillo cave is a well-known site because of its Paleolithic archaeology and parietal rock art. This paper is focused on the human remains found by V. Cabrera in the Mousterian Unit XX assigned to MIS 4 and early MIS 3. The fossils consist of one upper left second premolar (ULP4), one incomplete proximal hand phalanx, and one partial femoral head. The tooth and the phalanx were assigned to adults, whereas the femoral head belonged to an immature individual due to the absence of fusion traces to the metaphyseal surface. The external morphology and metrical characterization of the Castillo-1466 (ULP4) tooth crown was quantified and compared to the variability of other Neanderthal dental remains and a sample of modern human populations. We also quantified its 3D enamel thickness distribution, its roots morphology, as well as the presence of chipping, and their possible relation to masticatory or paramasticatory activities. Castillo-1466 shows crown dimensions compatible with middle-sized Neanderthal teeth, but with a remarkably thicker enamel than other Neanderthal premolars, such as Marillac 13. The femoral head and the hand phalanx fragment are compared to published values for Neanderthals, although both partial fossils lack diagnostic features precluding any clear taxonomic diagnostic. Therefore, their attribution to Neanderthals is assumed based on the dating of the layers in which they were discovered. El Castillo cave Mousterian fossils represent another contribution to the knowledge of the Middle Paleolithic populations of Northern Spain, where different sites along the Cantabrian mountains yielded several human remains assigned to MIS 4 and early MIS 3.

RevDate: 2023-09-14
CmpDate: 2023-09-12

Aquino Y, Bisiaux A, Li Z, et al (2023)

Dissecting human population variation in single-cell responses to SARS-CoV-2.

Nature, 621(7977):120-128.

Humans display substantial interindividual clinical variability after SARS-CoV-2 infection[1-3], the genetic and immunological basis of which has begun to be deciphered[4]. However, the extent and drivers of population differences in immune responses to SARS-CoV-2 remain unclear. Here we report single-cell RNA-sequencing data for peripheral blood mononuclear cells-from 222 healthy donors of diverse ancestries-that were stimulated with SARS-CoV-2 or influenza A virus. We show that SARS-CoV-2 induces weaker, but more heterogeneous, interferon-stimulated gene activity compared with influenza A virus, and a unique pro-inflammatory signature in myeloid cells. Transcriptional responses to viruses display marked population differences, primarily driven by changes in cell abundance including increased lymphoid differentiation associated with latent cytomegalovirus infection. Expression quantitative trait loci and mediation analyses reveal a broad effect of cell composition on population disparities in immune responses, with genetic variants exerting a strong effect on specific loci. Furthermore, we show that natural selection has increased population differences in immune responses, particularly for variants associated with SARS-CoV-2 response in East Asians, and document the cellular and molecular mechanisms by which Neanderthal introgression has altered immune functions, such as the response of myeloid cells to viruses. Finally, colocalization and transcriptome-wide association analyses reveal an overlap between the genetic basis of immune responses to SARS-CoV-2 and COVID-19 severity, providing insights into the factors contributing to current disparities in COVID-19 risk.

RevDate: 2023-10-21

Augoyard M, Zanolli C, Santos F, et al (2023)

Evaluation of age, sex, and ancestry-related variation in cortical bone and dentine volumes in modern humans, and a preliminary assessment of cortical bone-dentine covariation in later Homo.

Journal of anthropological sciences = Rivista di antropologia : JASS, 100:143-169.

Cortical bone and dentine share similarities in their embryological origin, development, and genetic background. Few analyses have combined the study of cortical bone and dentine to quantify their covariation relative to endogenous and exogenous factors. However, knowing how these tissues relate in individuals is of great importance to decipher the factors acting on their evolution, and ultimately to understand the mechanisms responsible for the different patterns of tissue proportions shown in hominins. The aims of this study are to examine age-, sex-, and ancestry-related variation in cortical bone and dentine volumes, and to preliminary assess the possible covariation between these tissues in modern humans and in five composite Neandertals. The modern analytical sample includes 12 immature individuals from France and 49 adults from France and South Africa. Three-dimensional tissue proportions were assessed from microtomographic records of radii and permanent maxillary canines. Results suggest ontogenic differences and a strong sexual dimorphism in cortical bone and dentine developments. The developmental pattern of dentine also seems to vary according to individual's ancestry. We measure a stronger covariation signal between cortical bone and dentine volumes than with any other dental tissue. A more complex covariation pattern is shown when splitting the modern sample by age, sex, and ancestry, as no signal is found in some subsamples while others show a covariation between cortical bone and either crown or radicular dentine. Finally, no difference in cortical bone volume is noticed between the modern young adults and the five young adult composite Neandertals from Marine Isotopic Stages (MIS) 5 and 3. Greater dentine Cortical bone and dentine (co)variation volumes are measured in the MIS 5 chimeric Neandertals whereas a strong interpopulation variation in dentine thickness is noticed in the MIS 3 chimeric Neandertals. Further research on the cortical bonedentine covariation will increase understanding of the impact of endogenous and exogenous factors on the development of the mineralized tissues.


ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

SUPPORT ESP: Click covers to order from Amazon
The ESP project will earn a commission.


The first fossil recognized to be an ancestral human was found in the Neander Valley (thal in German) in 1856. William King suggested Homo neanderthalensis (human from the Neander Valley) as the scientific name for the specimen — hence Neanderthal became the common name by which this early human became known. Now Neanderthal genomes have been sequenced, more is known about their path to extinction, and the existence of Neanderthal culture, including music, has been established. To understand the evolutionary path of the hominid line, one must be familiar with Homo neanderthalensis. These books are highly recommended. R. Robbins

Electronic Scholarly Publishing
961 Red Tail Lane
Bellingham, WA 98226

E-mail: RJR8222 @

Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin and even a collection of poetry — Chicago Poems by Carl Sandburg.


ESP now offers a large collection of user-selected side-by-side timelines (e.g., all science vs. all other categories, or arts and culture vs. world history), designed to provide a comparative context for appreciating world events.


Biographical information about many key scientists (e.g., Walter Sutton).

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )