Biology subjects

Kuhlwilm, M.

Publications and source records attributed to Kuhlwilm, M..

At least 19 recordsLinked to original sources

bioRxiv2026

A meta-analysis of ancient and present-day Central Eurasian genome data to revise archaic hominin ancestry

Archaic introgression has shaped the evolutionary history of Eurasian populations, yet Central Eurasian region remains understudied despite being at the crossroads of ancient human migration. Here, we analyzed the whole-genome data of five Central Eurasian (CE) individuals from Early Bronze Age (EBA) and five present-day CE individuals to characterize the archaic introgression landscape. We estimated that archaic introgression from Neanderthal and Denisovan archaic hominins comprises approximately 2.2% of the Central Eurasian genomes. Both amount and chromosomal distribution of archaic introgression remained largely unchanged between the EBA and present-day CE individuals. Putative introgressed fragments matching the Altai Neanderthal and the Altai Denisovan were retrieved. Our results suggest that while the archaic introgression levels seemingly remained stable over the past several thousand years, larger modern CE genomes panels will be required to fully characterize the genomic landscape of archaic ancestry in the region.

genomics↗

bioRxiv2026

sstar2: A Python Package for S*-based Archaic Introgression Detection with Machine Learning

Detecting introgressed genomic fragments from unsampled or extinct source populations remains challenging. The S* statistic is widely used for this purpose, but the original sstar implementation relies on generalized additive models to smooth quantile-specific values precomputed from fixed count bins, requiring simulations with fixed numbers of segregating sites. Here, we present sstar2, a Python update that replaces this procedure with quantile regression to directly estimate S* thresholds at specified null quantiles from simulated genomic windows. We benchmarked sstar2 against the original sstar, linear quantile regression, and random forest quantile regression across three demographic models with both phased and unphased simulated data. sstar2 showed the best overall performance among the evaluated methods, with the most pronounced improvement under a challenging demographic model of ghost introgression in bonobos. These results show that sstar2 improves S* threshold calibration while making S*-based introgression analyses more flexible and compatible with modern simulation workflows.

bioinformatics↗

bioRxiv2026

GAISHI: A Python Package for Detecting Ghost Introgression with Machine Learning

SummaryGhost introgression is a challenging problem in population genetics. Recent studies have explored supervised learning models, namely logistic regression and UNet++, to detect genomic footprints of ghost introgression. However, their applicability is limited because existing implementations are tailored to tasks in their respective publications, but not available as user-friendly software implementations. Here, we present GAISHI, a Python package for identifying ghost introgressed segments and alleles using multiple machine learning algorithms and demonstrate its usage in different introgression scenarios. Availability and implementationGAISHI is available on GitHub under the GNU General Public License v3.0. The source code can be found at https://github.com/xin-huang/gaishi.

bioinformatics↗

bioRxiv2026

Targeted Chromosomal Sequencing of Wild Bonobos Identifies a Genetically Distinct Subpopulation East of the Lomami River

Bonobos (Pan paniscus), an endangered species, have for decades been genetically understudied, partly due to difficulties in obtaining high-quality samples. The study of their genome is important not only for understanding their evolution, but also for improving conservation efforts, including population management, diversity and inbreeding assessment, and tracking rescued individuals to combat illegal wildlife trafficking. Here, we use chromosome 21 target capture data from 156 non-invasively collected faecal samples from wild bonobos to perform a comprehensive analysis of their population structure. We confirm the existence of three previously suggested subpopulations identified here as Western, Central and Eastern bonobos which are defined by natural barriers of gene flow such as the Lomami River. By estimating levels of inbreeding, diversity and differentiation, we find support for isolation of mainly Western and Eastern populations and add information on the dispersal routes of their ancestors. We infer split times and separation of these populations and apply a genetic framework to geolocalize samples of unknown origin, showing that locations of their potential origin can be estimated with a precision of up to a median of [~]50 km. Our study provides valuable insight into the evolution and population structure of bonobos and reveals how rivers act as strong barriers between populations. It also offers resources for conservation efforts and highlights the need to monitor bonobo populations more closely, in particular isolated ones. ImpactBonobos have been difficult to study genetically due to their remote forest habitat and endangered status. Here we used non-invasive sampling and chromosome 21 target capture sequencing to perform the most detailed analysis to date of their population structure. We find three main subpopulations and genetic differentiation influenced by river barriers, especially with populations found on the Eastern side of the Lomami river. This data will be useful for identifying the geographic origin of confiscated samples and thus aid bonobo conservation efforts.

bioinformatics↗

bioRxiv2025

Genetic insights into Iron Age Saka culture: Ancient DNA analysis of the Boz-Barmak burial ground, Kyrgyzstan

The nomadic cultures of the Iron Age played an important role in shaping the genetic and cultural landscape of Eurasian populations. Yet despite its key geographical location, the Central Eurasian region remains underrepresented in ancient DNA studies of humans. We address this gap through genomic analysis of 12 individuals from the Boz-Barmak burial site in Kyrgyzstan associated with Saka pastoralists (4th-2nd centuries BCE), 9 of which yielded low-coverage genomes. Genetic clustering analysis placed these individuals within the genetic variation of ancient and modern Central Eurasian and Siberian populations. We found no evidence of first-degree relatives in a kinship analysis, however a network of second- and third-degree relationships seems to be present. Notably, all male individuals share the same Y-chromosomal haplotype, common in present-day Kyrgyz and Tajik groups, while mitochondrial DNA showed comparably high diversity, with distinct haplogroups observed across the analysed individuals. These findings are in line with archaeological and ethnographic evidence of patrilocality in Early Iron Age Saka, where male lineages remained stable across generations, while female mobility contributed to genetic diversity. Our study complements our understanding of the interplay between kinship, social organization and population history in nomadic cultures.

genomics↗

bioRxiv2025

Genomic Landscapes of Natural Selection in Great Apes

BackgroundGreat apes are a primate clade with unique biological features. The different species and subspecies have adapted to their respective habitats and followed various evolutionary trajectories influencing their diversity. Hence, studying patterns of natural selection across this clade is an important aspect in understanding their biology. ResultsWe analyzed a curated panel of genomic diversity for bonobos, chimpanzees, eastern and western gorillas, and Bornean and Sumatran orangutans to explore their selection landscapes. A genome-wide screen was conducted for recent positive and long-term balancing selection, revealing candidate loci potentially related to sensory and immune systems, environmental pressures such as diet or altitude, and reproductive strategies in these species. In addition, the distribution of fitness effects (DFE) was determined, along with the correlations of DFEs across lineages. ConclusionsWe interpret the potential biological meaning of the landscapes of recent positive and long-term balancing selection in our closest living relatives, revealing novel lineage-specific candidate genes and gene categories, as well as recurrent targets across lineages. Our investigation of the deleterious DFE indicates that most non-synonymous mutations fall into either the nearly neutral or strongly deleterious categories, with high correlations between closely related lineages.

evolutionary biology↗

bioRxiv2025

SAI: A Python Package for Statistics for Adaptive Introgression

Adaptive introgression is an important evolutionary process, yet widely used summary statistics--such as the number of uniquely shared sites and the quantile of the derived allele frequencies in such sites--lack accessible implementations, limiting reproducibility and methodological clarity. Here, we present SAI, a Python package for computing these statistics, and apply it to three datasets. First, using the 1000 Genomes Project data, we replicated previously reported candidate regions and identified additional ones, including a region detected by studies using supervised deep learning. Second, reanalysis of a Lithuanian genome dataset revealed no candidates in the HLA region. Finally, we investigated bonobo introgression into central chimpanzees and identified a candidate region that overlaps a high-frequency Denisovan-introgressed haplotype block reported in modern Papuans--an intriguing co-occurrence across divergent lineages. Discrepancies with prior results highlight the importance of transparent and reproducible analysis workflows, especially as machine learning becomes increasingly prevalent in evolutionary genomics.

evolutionary biology↗

bioRxiv2025

A curated great ape genome diversity panel

Studying the genetic diversity of non-human great apes is important for research questions in evolution as well as human diversity and disease. Genomic data of the three great ape clades (Pan, Gorilla, Pongo) has been published across multiple studies over more than one decade. However, unlike in humans, no comprehensive dataset on great ape diversity is available, due to different scopes of the original studies. Here, we present a curated dataset of 332 high coverage ([≥]12-fold) whole genomes, including 198 chimpanzee, 16 bonobo, 77 gorilla and 41 orangutan individuals sequenced on the Illumina platform. By integrating data from captive individuals, we contextualize them with data from wild individuals. We discuss issues with previously published data leading to removal of individuals due to low sequencing depth, missing data, or occurrence of duplicate individuals. This resource of files in CRAM and gVCF format, as well as segregating sites per clade, will allow researchers to address questions related to human and great ape evolution and diversity in a comparative manner.

genomics↗

bioRxiv2024

Deep genetic substructure within bonobos

Establishing the genetic and geographic structure of populations is fundamental both to understand their evolutionary past and preserve their future, especially for endangered species. Nevertheless, the patterns of genetic population structure are unknown for most endangered species, including some of our closest living relatives. This is the case of bonobos (Pan paniscus) which together with chimpanzees (Pan troglodytes) are humans closest living relatives. Chimpanzees live across equatorial Africa and are classified into four subspecies (Groves, 2001), with some genetic population substructure even within subspecies. Conversely, bonobos live exclusively in the Democratic Republic of Congo and are considered a homogeneous group with low genetic diversity (Fischer et al. 2011) despite some population structure inferred from mtDNA. Nevertheless, mtDNA aside, their genetic structure remains unknown, hampering our understanding of the species and conservation efforts. Placing bonobos genetics in space is however challenging because, being endangered, only non-invasive sampling is possible for wild individuals. Here, we jointly analyse the exomes and mtDNA from 20 wild-born bonobos, the whole-genomes of 10 captive bonobos and the mtDNA of 61 wild individuals. We identify three genetically distinct bonobo groups of inferred Central, Western and Far-Western geographic origin within the bonobo range. We estimate the split time between the central and western populations to [~]145,000 years ago, and genetic differentiation to be in the order of that of the closest chimpanzee subspecies. We identify putative signatures of differential genetic adaptation among populations for genes associated with homeostasis, metabolism and the nervous system. Furthermore, our estimated long-term Ne for Far-West ([~]3,000) is among the lowest estimated for any great ape lineage. Our results highlight the need of attention to bonobo substructure, both in terms of research and conservation. Highlights- We identified three genetically distinct populations of bonobos, inferred as having Central, Western and Far-Western geographic origin within the species range. The estimated split time is [~]145,000 years ago for the Central and Western populations, and [~]60,000 years ago for the two Western populations. - The genetic differentiation between the Central and Far-Western bonobo populations is in the order of that between Central and Eastern chimpanzee subspecies, while the genetic differentiation among Western bonobo populations is similar to that among human groups. - Once substructure is accounted for, we infer a long-term effective population size (Ne) of only [~]3,000 for Far-Western bonobos, genetic isolation and inbreeding.

evolutionary biology↗

bioRxiv2024

Screening great ape museum specimens for DNA viruses

Natural history museum collections harbour a record of wild species from the past centuries, providing a unique opportunity to study animals as well as their infectious agents. Thousands of great ape specimens are kept in these collections, and could become an important resource for studying the evolution of DNA viruses. Their genetic material is likely to be preserved in dry museum specimens, as reported previously for monkeypox virus genomes from historical orangutan specimens. Here, we screened 209 great ape museum specimens for 99 different DNA viruses, using hybridization capture coupled with short-read high-throughput sequencing. We determined the presence of multiple viruses within this dataset from historical specimens and obtained several near-complete viral genomes. In particular, we report high-coverage (>18-fold) hepatitis B virus genomes from one gorilla and two chimpanzee individuals, which are phylogenetically placed within clades infecting the respective host species.

genomics↗

bioRxiv2024

A complete mitochondrial genome of a Roman-era Plasmodium falciparum

Malaria has historically been one of the leading infection-related causes of death in human populations. To this day, it continues to pose a significant public health threat in African countries, particularly among children. Humans are affected by five Plasmodium species, with Plasmodium falciparum being the most lethal. The study of pathogenic DNA from ancient human remains has been vital in understanding the origin, evolution, and virulence of human-infecting pathogens. However, there have been no complete pre-20th century mitochondrial DNA (mtDNA) or genomic sequences of Plasmodium falciparum reported to date. This gap in knowledge makes it difficult to understand the genetic dynamics of this pathogen in the past. The difficulty in identifying ancient malaria cases through bioarchaeology and the infrequent presence of Plasmodium DNA in ancient bones contribute to these limitations. Here, we present the first complete mtDNA genome of P. falciparum recovered from an archaeological skeleton (a 2nd century CE Roman individual from Italy). The study of the 43-fold mtDNA genome supports the hypothesis of an Indian origin for P. falciparum in Europe and provides evidence for the genetic continuity of this lineage over the past 2,000 years. Additionally, our research highlights that extensive sampling may be necessary for malaria screening to gain insights into the evolution of this vector-borne disease from archaeological samples.

genomics↗

bioRxiv2023

Population interconnectivity shapes the distribution and complexity of chimpanzee cumulative culture

While cumulative culture is a hallmark of hominin evolution, its origins can be traced back to our common ancestor with chimpanzees. Here we investigate the evolutionary origins of chimpanzee cumulative culture, and why it remained incipient. To trace cultural transmission among the four chimpanzee subspecies, we compared between-population networks based on genetic markers of recent migration and shared cultural traits. We show that limited levels of interconnectivity favored the emergence of a few instances of cumulative culture in chimpanzees. As in humans, cultural complexification likely happened in steps, with between-community transmission promoting incremental changes and repurposing of technologies. We propose that divergence in social patterns led to increased between-group mobility in Homo, propelling our lineage towards a trajectory of irreversible dependence on cultural exchange and complexification. One-Sentence SummaryPopulation interconnectivity through migration explains the origins of chimpanzee cumulative culture and why it remained incipient

evolutionary biology↗

bioRxiv2023

The landscape of tolerated genetic variation in humans and primates

Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole genome sequencing data for 809 individuals from 233 primate species, and identified 4.3 million common protein-altering variants with orthologs in human. We show that these variants can be inferred to have non-deleterious effects in human based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases. One Sentence SummaryDeep learning classifier trained on 4.3 million common primate missense variants predicts variant pathogenicity in humans.

genomics↗

bioRxiv2023

A global catalog of whole-genome diversity from 233 primate species

The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology, and is urgent given severe threats these species are facing. Here, we present high coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human-specific. This study will open a wide range of research avenues for future primate genomic research. One-Sentence SummaryThe whole genome sequences of 233 primate species provide insight into the determinants of genetic diversity, phylogenomics, and human uniqueness.

genomics↗

bioRxiv2023

Genome-wide coancestry reveals details of ancient and recent male-driven reticulation in baboons

Baboons (genus Papio) are a morphologically and behaviorally diverse clade of catarrhine monkeys that have experienced hybridization between phenotypically and genetically distinct phylogenetic species. We used high coverage whole genome sequences from 225 wild baboons representing 19 geographic localities to investigate population genomics and inter-species gene flow. Our analyses provide an expanded picture of evolutionary reticulation among species and reveal novel patterns of population structure within and among species, including differential admixture among conspecific populations. We describe the first example of a baboon population with a genetic composition that is derived from three distinct lineages. The results reveal processes, both ancient and recent, that produced the observed mismatch between phylogenetic relationships based on matrilineal, patrilineal, and biparental inheritance. We also identified several candidate genes that may contribute to species-specific phenotypes. One-Sentence SummaryGenomic data for 225 baboons reveal novel sites of inter-species gene flow and local effects due to differences in admixture.

evolutionary biology↗

bioRxiv2022

Ghost admixture in eastern gorillas

Archaic admixture has had a significant impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. Within the great apes archaic admixture has been identified in chimpanzees and bonobos, but the possibility of such events has not been explored in other species. Here, we address this question using high-coverage whole genome sequences from all four extant gorilla subspecies, including six newly sequenced eastern gorillas from previously unsampled geographic regions. Using Approximate Bayesian Computation (ABC) with neural networks to model the demographic history of gorillas, we find a signature of admixture from an archaic ghost lineage into the common ancestor of eastern gorillas, but not western gorillas. We infer that up to 3% of the genome of these individuals is introgressed from an archaic lineage that diverged more than 3 million years ago from the common ancestor of all extant gorillas. This introgression event took place before the split of mountain and eastern lowland gorillas, likely more than 40 thousand years ago, and may have influenced perception of bitter taste in eastern gorillas. When comparing the introgression landscapes of gorillas, humans and bonobos, we find a consistent depletion of introgressed fragments on the X chromosome across these species. However, depletion in protein-coding content is not detectable in eastern gorillas, possibly as a consequence of stronger genetic drift in this species.

evolutionary biology↗

bioRxiv2022

sstar: A Python package for detecting archaic introgression from population genetic data with S*

S* is a widely used statistic for detecting archaic admixture from population genetic data. Previous studies used freezing-archer to apply S*, which is only directly applicable to the specific case of Neanderthal and Denisovan introgression in Papuans. Here, we implemented sstar for a more general purpose. Compared with several tools, including SPrime, SkovHMM, and ArchaicSeeker2.0, for detecting introgressed fragments with simulations, our results suggest that sstar is robust to differences in demographic models, including ghost introgression and two-source introgression. We believe sstar will be a useful tool for detecting introgressed fragments in various scenarios and in non-human species.

genomics↗

bioRxiv2022

Differential sensory and immune gene evolution in sea turtles with contrasting demographic and life histories

Sea turtles represent an ancient lineage of marine vertebrates that evolved from terrestrial ancestors over 100 MYA, yet the genomic basis of the unique physiological and ecological traits enabling these species to thrive in diverse marine habitats remains largely unknown. Additionally, many populations have drastically declined due to anthropogenic activities over the past two centuries, and their recovery is a high global conservation priority. We generated and analyzed high-quality reference genomes for the leatherback (Dermochelys coriacea) and green (Chelonia mydas) turtles, representing the two extant sea turtle families. These genomes are highly syntenic and homologous, but localized regions of non-collinearity were associated with higher copy numbers of immune, zinc-finger, and olfactory receptor (OR) genes in green turtles, with ORs related to waterborne odorants greatly expanded in green turtles. Our findings suggest that divergent evolution of these key gene families may underlie immunological and sensory adaptations assisting navigation, occupancy of neritic versus pelagic environments, and diet specialization. Reduced collinearity was especially prevalent in microchromosomes, with greater gene content, heterozygosity, and genetic distances between species, supporting their critical role in vertebrate evolutionary adaptation. Finally, diversity and demographic histories starkly contrasted between species, indicating that leatherback turtles have had a low yet stable effective population size, exhibit extremely low diversity compared to other reptiles, and harbor a higher genetic load compared to green turtles, reinforcing concern over their persistence under future climate scenarios. These genomes provide invaluable resources for advancing our understanding of evolution and conservation best practices in an imperiled vertebrate lineage. Statement of significanceSea turtle populations have undergone recent global declines. We analyzed de novo assembled genomes for both extant sea turtle families through the Vertebrate Genomes Project to inform their conservation and evolutionary biology. These highly conserved genomes were differentiated by localized gene-rich regions of divergence, particularly within microchromosomes, suggesting that these genomic elements play key functional roles in the evolution of sea turtles and possibly other vertebrates. We further demonstrate that dissimilar evolutionary histories impact standing genomic diversity and genetic load, and are critical to consider when using these metrics to assess adaptive potential and extinction risk. Our results also demonstrate how reference genome quality impacts inferences of comparative and conservation genomics analyses that need to be considered in their application.

genomics↗