Biology subjects

Webster, T. H.

Publications and source records attributed to Webster, T. H..

13 recordsLinked to original sources

bioRxiv2026

Human ancestors interbred with two distinct populations of distant relatives

Ancient DNA has shown that a distantly-related "superarchaic" population interbred first with the ancestors of Neanderthals and Denisovans and later with Denisovans themselves. Other work has shown that a superarchaic population interbred with the African ancestors of all modern humans. But it is not yet clear whether these events involved the same superarchaic population. Here, we use the distribution of derived alleles among populations to evaluate hypotheses about superarchaics and their relationship to other hominins of the Pleistocene and Holocene. We find evidence for at least two distinct superarchaic populations. The one contributing to archaic Eurasian populations (Denisovans and Neanderthal-Denisovan ancestors) diverged earlier from the human lineage than did the one contributing to early moderns in Africa. This latter superarchaic contributed a large fraction--about 20%--to the ancestry of modern humans. These findings reveal previously unrecognized structure among hominin populations in the Pleistocene. Significance statementGenetic data have shown that all human populations are mixtures. Since the last ice age, the populations mixing have been relatively close relatives--separated by a few tens of thousands of years or less. Earlier in the Pleistocene, there was mixing between more distantly-related populations, with separation times in excess of a million years. Here, we document admixture events involving two distinct populations, each of which had separated from the human lineage well over a million years ago. One of these was apparently Eurasian, because it mixed with archaic Eurasian populations. The other was apparently African, because it mixed with the African ancestors of modern humans. This latter event was remarkable, because the distant relative contributed such a large fraction--about 20%--to the ancestry of modern humans. These results show that during the Pleistocene, the earth was home to hominin populations far more distantly related than any pair of modern human populations, with separation times similar to that of bonobos and chimpanzees. These distantly-related pairs existed not only on separate continents, but also within the African continent. And in spite of the large differences between them, these populations were able to interbreed.

evolutionary biology↗

bioRxiv2023

Sequence-based machine learning reveals 3D genome differences between bonobos and chimpanzees

Phenotypic divergence between closely related species, including bonobos and chimpanzees (genus Pan), is largely driven by variation in gene regulation. The 3D structure of the genome mediates gene expression; however, genome folding differences in Pan are not well understood. Here, we apply machine learning to predict genome-wide 3D genome contact maps from DNA sequence for 56 bonobos and chimpanzees, encompassing all five extant lineages. We use a pairwise approach to estimate 3D divergence between individuals from the resulting contact maps in 4,420 1 Mb genomic windows. While most pairs were similar,[~] 17% were predicted to be substantially divergent in genome folding. The most dissimilar maps were largely driven by single individuals with rare variants that pro-duce unique 3D genome folding in a region. We also identified 89 genomic windows where bonobo and chimpanzee contact maps substantially diverged, including several windows harboring genes associated with traits implicated in Pan phenotypic divergence. We used in silico mutagenesis to identify 51 3D-modifying variants in these bonobo-chimpanzee diver-gent windows, finding that 34 or 66.67% induce genome folding changes via CTCF binding motif disruption. Our results reveal 3D genome variation at the population-level and identify genomic regions where changes in 3D folding may contribute to phenotypic differences in our closest living relatives.

genomics↗

bioRxiv2023

Incomplete dosage balance and dosage compensation in the ZZ/ZW Gila monster (Heloderma suspectum) revealed by de novo genome assembly

Reptiles exhibit a variety of modes of sex determination, including both temperature-dependent and genetic mechanisms. Among those species with genetic sex determination, sex chromosomes of varying heterogamety (XX/XY and ZZ/ZW) have been observed with different degrees of differentiation. Karyotype studies have demonstrated that Gila monsters (Heloderma suspectum) have ZZ/ZW sex determination and this system is likely homologous to the ZZ/ZW system in the Komodo dragon (Varanus komodoensis), but little else is known about their sex chromosomes. Here, we report the assembly and analysis of the Gila monster genome. We generated a de novo draft genome assembly for a male using 10X Genomics technology. We further generated and analyzed short-read whole genome sequencing and whole transcriptome sequencing data for three males and three females. By comparing female and male genomic data, we identified four putative Z-chromosome scaffolds. These putative Z-chromosome scaffolds are homologous to Z-linked scaffolds identified in the Komodo dragon. Further, by analyzing RNAseq data, we observed evidence of incomplete dosage compensation between the Gila monster Z chromosome and autosomes and a lack of balance in Z-linked expression between the sexes. In particular, we observe lower expression of the Z in females (ZW) than males (ZZ) on a global basis, though we find evidence suggesting local gene-by-gene compensation. This pattern has been observed in most other ZZ/ZW systems studied to date and may represent a general pattern for female heterogamety in vertebrates.

evolutionary biology↗

bioRxiv2022

Estimating Pan evolutionary history from nucleotide site patterns

Introgression appears increasingly ubiquitous in the evolutionary history of various taxa, including humans. However, accurately estimating introgression is difficult, particularly when 1) there are many parameters, 2) multiple models fit the data well, and 3) parameters are not simultaneously estimated. Here, we use the software Legofit to investigate the evolutionary history of bonobos (Pan paniscus) and chimpanzees (P. troglodytes) using whole genome sequences. This approach 1) ignores within-population variation, reducing the number of parameters requiring estimation, 2) allows for model selection, and 3) simultaneously estimates all parameters. We tabulated site patterns from the autosomes of 71 bonobos and chimpanzees representing all five extant Pan lineages. We then compared previously proposed demographic models and estimated parameters using a deterministic approach. We further considered sex bias in Pan evolutionary history by analyzing the site patterns from the X chromosome. Introgression from bonobos into the ancestor of eastern and central chimpanzees and from western into eastern chimpanzees best explained the autosomal site patterns. This second event was substantial with an estimated 0.21 admixture proportion. Estimates of effective population size and most divergence dates are consistent with previous findings; however, we observe a deeper divergence within chimpanzees at 987 ka. Finally, we identify male-biased reproduction in Pan evolutionary history and suggest that western to eastern chimpanzee introgression was driven by western males mating with eastern females.

genomics↗

bioRxiv2021

Signatures of adaptive evolution in platyrrhine primate genomes

The family Cebidae (capuchin and squirrel monkeys) form a remarkable platyrrhine clade exhibiting among the largest primate encephalisation quotients. Each cebid lineage is characterised by notable lineage-specific traits, with capuchins showing striking similarities to Hominidae including high sensorimotor intelligence with tool use, advanced cognitive abilities, and behavioural flexibility. Here, we take a comparative genomics approach, analysing five cebid branches including successive lineages, to infer a stepwise timeline for cebid adaptive evolution. We uncover candidate targets of selection across various periods of cebid evolution that may underlie the emergence of lineage-specific traits. Our analyses highlight shifting and sustained selective pressures on genes related to brain development, longevity, reproduction, and morphology, including evidence for cumulative and diversifying neurobiological adaptations over cebid evolutionary history. In addition to generating a new, high-quality reference genome assembly for robust capuchins, our results lend to a better understanding of the adaptive diversification of this distinctive primate clade.

genomics↗

bioRxiv2021

Genomic and demographic processes differentially influence genetic variation across the X chromosome

Mutation, recombination, selection, and demography affect genetic variation across the genome. Increased mutation and recombination both lead to increases in genetic diversity in a region-specific manner, while complex demographic patterns shape patterns of diversity on a more global scale. The X chromosome is particularly interesting because it contains several distinct regions that are subject to different combinations and strengths of these processes, notably the pseudoautosomal regions (PARs) and the X-transposed region (XTR). The X chromosome thus can serve as a unique model for studying how genetic and demographic forces act in different contexts to shape patterns of observed variation. Here we investigate diversity, divergence, and linkage disequilibrium in each region of the X chromosome using genomic data from 26 human populations. We find that both diversity and substitution rate are consistently elevated in PAR1 and the XTR compared to the rest of the X chromosome. In contrast, linkage disequilibrium is lowest in PAR1 and highest on the non-recombining X chromosome, with the XTR falling in between, suggesting that the XTR (usually included in the non-recombining X) may need to be considered separately in future studies. We also observed strong population-specific effects on genetic diversity; not only does genetic variation differ on the X and autosomes among populations, but the effects of linked selection on the X relative to autosomes have been shaped by population-specific history. The substantial variation in patterns of variation across these regions provides insight into the unique evolutionary history contained within the X chromosome. Significance StatementDemography and selection affect the X chromosome differently from non-sex chromosomes. However, the X chromosome can be subdivided into multiple distinct regions that facilitate even more fine-scaled assessment of these processes. Here we study regions of the human X chromosome in 26 populations to find evidence that recombination may be mutagenic in humans and that the X-transposed region may undergo recombination. Further we observe that the effects of selection and demography act differently on the X chromosome relative to the autosomes across human populations. Together, our results highlight profound regional differences across the X chromosome, simultaneously making it an ideal system for exploring the action of evolutionary forces as well as necessitating its careful consideration and treatment in genomic analyses.

genetics↗

bioRxiv2020

Soft sweeps predominate recent positive selection in bonobos (Pan paniscus) and chimpanzees (Pan troglodytes)

Two modes of positive selection have been recognized: 1) hard sweeps that result in the rapid fixation of a beneficial allele typically from a de novo mutation and 2) soft sweeps that are characterized by intermediate frequencies of at least two haplotypes that stem from standing genetic variation or recurrent de novo mutations. While many populations exhibit both hard and soft sweeps throughout the genome, there is increasing evidence that soft sweeps, rather than hard sweeps, are the predominant mode of adaptation in many species, including humans. Here, we use a supervised machine learning approach to assess the extent of completed hard and soft sweeps in the closest living relatives of humans: bonobos and chimpanzees (genus Pan). We trained convolutional neural network classifiers using simulated data and applied these classifiers to population genomic data for 71 individuals representing all five extant Pan lineages, of which we successfully analyzed 60 individuals from four lineages. We found that recent adaptation in Pan is largely the result of soft sweeps, ranging from 73.1 to 97.7% of all identified sweeps. While few hard sweeps were shared among lineages, we found that between 19 and 267 soft sweep windows were shared by at least two lineages. We also identify novel candidate genes subject to recent positive selection. This study emphasizes the importance of shifts in the physical and social environment, rather than novel mutation, in shaping recent adaptations in bonobos and chimpanzees.

genomics↗

bioRxiv2020

High-throughput phenotyping methods for quantifying hair fiber morphology

Quantifying the continuous variation in human scalp hair morphology is of interest to anthropologists, geneticists, dermatologists and forensic scientists, but existing methods for studying hair form are time-consuming and not widely used. Here, we present a high-throughput sample preparation protocol for the imaging of both longitudinal (curvature) and cross-sectional scalp hair morphology. Additionally, we describe and validate a new Python package designed to process longitudinal and cross-sectional hair images, segment them, and provide measurements of interest. Lastly, we apply our methods to an admixed African-European sample (n=140), demonstrating the benefit of quantifying hair morphology over qualitative classification or racial categories, and providing evidence against the long-held belief that cross-sectional morphology predicts curvature.

bioinformatics↗

bioRxiv2020

Urine as a high-quality source of host genomic DNA from wild populations

The ability to generate genomic data from wild animal populations has the potential to give unprecedented insight into the population history and dynamics of species in their natural habitats. However, in the case of many species, it is impossible legally, ethically, or logistically to obtain tissues samples of high-quality necessary for genomic analyses. In this study we evaluate the success of multiple sources of genetic material (feces, urine, dentin, and dental calculus) and several capture methods (shotgun, whole-genome, exome) in generating genome-scale data in wild eastern chimpanzees (Pan troglodytes schweinfurthii) from Gombe National Park, Tanzania. We found that urine harbors significantly more host DNA than other sources, leading to broader and deeper coverage across the genome. Urine also exhibited a lower rate of allelic dropout. We found exome sequencing to be far more successful than both shotgun sequencing and whole-genome capture at generating usable data from low-quality samples such as feces and dental calculus. These results highlight urine as a promising and untapped source of DNA that can be noninvasively collected from wild populations of many species.

genomics↗

bioRxiv2019

Genetic relatedness cannot explain social bonds in black-and-white ruffed lemurs (Varecia variegata).

Fission-fusion social dynamics are common among a number of vertebrate taxa, and yet the factors shaping these variable associations among subgroup members have not been widely addressed. Associations may occur simply because of shared habitat preferences; however, social ties may also be influenced by genetic relatedness (kinship) or social attraction. Here, we investigate the association patterns of wild black-and-white ruffed lemurs, Varecia variegata, in Ranomafana National Park, Madagascar using behavioural, spatial (home range), and genetic data from twenty-four individually identified animals. We collected 40,840 records of group composition over a 17-month period and from this calculated pairwise association indices. We also used ranging coordinates and genetic samples to estimate patterns of spatial overlap and kinship, and then related these measures to patterns of affiliation. From these analyses, we found that dyadic ruffed lemur social associations were generally sparse and weak; that home range overlap was minimal; and that average relatedness within the community was low. We found no evidence that kinship was related to patterns of either spatial overlap or social association; instead, associations were primarily driven by space use. Moreover, social preferences were unrelated to kinship. While home range overlap explained most of the variation seen in social association, some variation remains unaccounted for, suggesting that other social, ecological, and biological factors such as shared resource defense or communal breeding might also play a role in social attraction. Our results further highlight the need to consider individual space use and nuances of species behavior when investigating social preference and social association more generally.

animal behavior and cognition↗

bioRxiv2019

Comparing the selective landscape of TLR7 and TLR8 across primates reveals unique sites under positive selection in Alouatta

Among primates, susceptibility to yellow fever (YFV), a single-stranded (ss) RNA virus, ranges from complete resistance to high susceptibility. Howler monkeys (genus Alouatta) are the most susceptible to YFV. In order to identify Alouatta-specific genetic factors that may be responsible for their susceptibility, we collected skin samples from howler monkey museum specimens of the species A. caraya and A. guariba clamitans. We compared the rate of nonsynonymous to synonymous (dN/dS) changes of Toll-like receptor (TLR) 7 and TLR8, the two genes responsible for detecting all ssRNA viruses, across the Primate order. Overall, we found that the TLR7 gene is under stronger purifying selection in howler monkeys compared to other New World and Old World primates, but TLR8 is under the same selective pressure. When we evaluated dN/dS at each codon, we found six codons under positive selection in Alouatta TLR8 and two codons under positive selection in TLR7. The changes in TLR7 are unique to A. guariba clamitans and are found in functionally important regions likely to affect detection of ssRNA viruses by TLR7/TLR8, as well as downstream signaling. These amino acid differences in A. guariba clamitans may play a role in YFV susceptibility. These results have implications for identifying genetic factors affecting YFV susceptibility in primates.

evolutionary biology↗

bioRxiv2018

Successful exome capture and sequencing in lemurs using human baits

ObjectivesWe assessed the efficacy of exome capture in lemurs using commercially available human baits.\n\nMaterials and MethodsWe used two human kits (Nimblegen SeqCap EZ Exome Probes v2.0; IDT xGen Exome Research Panel v1.0) to capture and sequence the exomes of wild Verreauxs sifakas (Propithecus verreauxi, n = 8), a lemur species distantly related to humans. For comparison, we also captured exomes of a primate species more closely related to humans (Macaca mulatta, n= 4). We mapped reads to both the human reference assembly and the most closely related reference for each species before calling variants. We used measures of mapping quality and read coverage to compare capture success.\n\nResultsWe observed high and comparable mapping qualities for both species when mapped to their respective nearest-relative reference genomes. When investigating breadth of coverage, we found greater capture success in macaques than sifakas using both nearest-relative and human assemblies. Exome capture in sifakas was still highly successful with more than 90% of annotated coding sequence in the sifaka reference genome captured, and 80% sequenced to a depth greater than 7x using Nimblegen baits. However, this success depended on probe design: the use of IDT probes resulted in substantially less callable sequence at low-to-moderate depths.\n\nDiscussionOverall, we demonstrate successful exome capture in lemurs using human baits, though success differed between kits tested. These results indicate that exome capture is an effective and economical genomic method of broad utility to evolutionary primatologists working across the entire primate order.

genomics↗

bioRxiv2018

Identifying, understanding, and correcting technical biases on the sex chromosomes in next-generation sequencing data

Mammalian X and Y chromosomes share a common evolutionary origin and retain regions of high sequence similarity. This sequence homology can cause the mismapping of short sequencing reads derived from the sex chromosomes and affect variant calling and other downstream analyses. Understanding and correcting this problem is critical for medical genomics and population genomic inference. Here, we characterize how sequence homology can affect analyses on the sex chromosomes and present XYalign, a new tool that: (1) facilitates the inference of sex chromosome complement from next-generation sequencing data; (2) corrects erroneous read mapping on the sex chromosomes; and (3) tabulates and visualizes important metrics for quality control such as mapping quality, sequencing depth, and allele balance. We show how these metrics can be used to identify XX and XY individuals across diverse sequencing experiments, including low and high coverage whole genome sequencing, and exome sequencing. We also show that XYalign corrects mismapped reads on the sex chromosomes, resulting in more accurate variant calling. Finally, we discuss how the flexibility of the XYalign framework can be leveraged for other use cases including the identification of aneuploidy on the autosomes. XYalign is available open source under the GNU General Public License (version 3).

bioinformatics↗