Biology subjects

Villanea, F. A.

Publications and source records attributed to Villanea, F. A..

6 recordsLinked to original sources

bioRxiv2026

Shared genetic foundation of the DHEAS pathway indicate similar extended childhoods in Neanderthals and modern humans

Adrenarche, the pre-pubertal rise in adrenal androgens, particularly dehydroepiandrosterone (DHEA) and its sulfated form DHEAS, is a critical driver of middle childhood cognitive and social development in modern humans. Compared to other apes, modern human adrenarche is more prolonged, with higher DHEAS levels. Whether this uniquely prolonged human adrenarche is a derived trait of Homo sapiens or has deeper hominin roots remains unresolved. Here, we examine the Neanderthal genetic variation in five key DHEAS biosynthesis genes (HSD3B2, CYP17A1, POR, CYB5A, SULT2A1). We also examine archaic introgression in these genes by comparing high-coverage Neanderthal genomes with globally diverse modern human sequences from the 1000 Genomes Project. We identify 29 Neanderthal-derived single nucleotide variants across these genes. Key steroidogenic genes in the biosynthesis pathway show no evidence of introgression, consistent with selection on pleiotropic regulators of steroidogenesis. In contrast, accessory genes carried introgressed Neanderthal haplotypes at moderate frequencies in non-African human populations, indicating Neanderthal variants are compatible with the human DHEAS synthesis pathway. All Neanderthal-specific variants were in non-coding regions, with three variants associated with reduced enzyme efficiency or DHEAS production in adults. Additionally, for all 29 positions, the modern human major allele is ancestral, and there is no evidence for a suite of novel adrenarche-extending variants. We conclude that the genetic foundation for extended adrenarche is shared between Homo sapiens and Neanderthals, and may have deeper hominin roots. Any phenotypic variation in adrenarche between modern humans and Neanderthals is more likely attributable to differential gene expression than to divergence in protein-coding sequences.

genomics↗

bioRxiv2023

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

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. We find diagnostic variants for the Denisovan-like MUC19 haplotype at high frequencies in admixed Latin American individuals, and at highest frequency in 23 ancient Indigenous American individuals, all predating population admixture with Europeans and Africans. We find that the Denisovan-like MUC19 haplotype is under positive selection and carries a higher copy number of a 30 base-pair variable number tandem repeat, and that copy numbers of this repeat are exceedingly high in American populations. Finally, some Neanderthals carry the Denisovan-like MUC19 haplotype, and that it was likely introgressed into human populations through Neanderthal introgression rather than Denisovan introgression. One-Sentence SummaryModern humans and Neanderthals carry a Denisovan variant of the MUC19 gene, which is under positive selection in populations of Indigenous American ancestry.

evolutionary biology↗

bioRxiv2022

Demographic history and genetic structure in pre-Hispanic Central Mexico

Aridoamerica and Mesoamerica are two distinct cultural areas that hosted numerous pre-Hispanic civilizations between 2,500 BCE and 1,521 CE. The division between these regions shifted southward due to severe droughts ca. 1,100 years ago, allegedly driving demographic changes and population replacement in some sites in central Mexico. Here, we present shotgun genome-wide data from 12 individuals and 26 mitochondrial genomes from eight pre-Hispanic archaeological sites across Mexico, including two at the shifting border of Aridoamerica and Mesoamerica. We find population continuity spanning the climate change episode and a broad preservation of the genetic structure across present-day Mexico for the last 2,300 years. Lastly, we identify a contribution to pre-Hispanic populations of northern and central Mexico from an ancient unsampled ghost population.

genomics↗

bioRxiv2021

On the Apportionment of Archaic Human Diversity

The apportionment of human genetic diversity within and between populations has been measured to understand human relatedness and demographic history. Likewise, the distribution of archaic ancestry in modern populations can be leveraged to better understand the interaction between our species and its archaic relatives, and the impact of natural selection on archaic segments of the human genome. Resolving these interactions can be difficult, as archaic variants in modern populations have also been shaped by genetic drift, bottlenecks, and gene flow. Here, we investigate the apportionment of archaic variation in Eurasian populations. We find that archaic genome coverage at the individual- and population-level present unique patterns in modern human population: South Asians have an elevated count of population-unique archaic SNPs, and Europeans and East Asians have a higher degree of archaic SNP sharing, indicating that population demography and archaic admixture events had distinct effects in these populations. We confirm previous observations that East Asians have more Neanderthal ancestry than Europeans at an individual level, but surprisingly Europeans have more Neandertal ancestry at a population level. In comparing these results to our simulated models, we conclude that these patterns likely reflect a complex series of interactions between modern humans and archaic populations.

genomics↗

bioRxiv2020

ABO genetic variation in Neanderthals and Denisovans

1Variation at the ABO locus was one of the earliest sources of data in the study of human population identity and history, and to this day remains widely genotyped due to its importance in blood and tissue transfusions. Here, we look at ABO blood type variants in our archaic relatives: Neanderthals and Denisovans. Our goal is to understand the genetic landscape of the ABO gene in archaic humans, and how it relates to modern human ABO variation. We found two derived Neanderthal variants of the O allele in the Siberian Neanderthals (O1 and O2), one of these variants is shared with an European Neanderthal, who is a heterozygote for this O1 variant and a rare cis-AB variant. The Denisovan individual is heterozygous for two ancestral variant of the O1 allele, similar to variants found widely in modern humans. Perhaps more surprisingly, the O2 allele variant found in Siberian Neanderthals can be found at low frequencies in modern Europeans and Southeast Asians, and the O1 allele variant found in Siberian and European Neanderthal is also found at very low frequency in modern East Asians. Our genetic distance analyses suggest both alleles survive in modern humans due to inbreeding with Neanderthals. We find that the sequence backgrounds of the surviving Neanderthal-like O alleles in modern humans retain a higher sequence divergence than other surviving Neanderthal genome fragments, supporting a view of balancing selection operating in the Neanderthal ABO alleles by retaining highly diverse haplotypes compared to portions of the genome evolving neutrally.

genomics↗

bioRxiv2018

Spectrum of Neandertal introgression across modern-day humans indicates multiple episodes of human-Neandertal interbreeding

1Neandertals and anatomically modern humans overlapped geographically for a period of over 30,000 years following human migration out of Africa. During this period, Neandertals and humans interbred, as evidenced by Neandertal portions of the genome carried by non-African individuals today. A key observation is that the proportion of Neandertal ancestry is [~]12-20% higher in East Asian individuals relative to European individuals. Here, we explore various demographic models that could explain this observation. These include distinguishing between a single admixture event and multiple Neandertal contributions to either population, and the hypothesis that reduced Neandertal ancestry in modern Europeans resulted from more recent admixture with a ghost population that lacked a Neandertal ancestry component (the \"dilution\" hypothesis). In order to summarize the asymmetric pattern of Neandertal allele frequencies, we compile the joint fragment frequency spectrum (FFS) of European and East Asian Neandertal fragments and compare it to both analytical theory and data simulated under various models of admixture. Using maximum likelihood and machine learning, we found that a simple model of a single admixture does not fit the empirical data, and instead favor a model of multiple episodes of gene flow into both European and East Asian populations. These findings indicate more long-term, complex interaction between humans and Neandertals than previously appreciated.

evolutionary biology↗