Biology subjects

Kuhlwilm, M.

Publications and source records attributed to Kuhlwilm, M..

25 records · Page 2Linked to original sources

bioRxiv2021

The genetic impact of an Ebola outbreak on a wild gorilla population

BackgroundNumerous Ebola virus outbreaks have occurred in Equatorial Africa over the past decades. Besides human fatalities, gorillas and chimpanzees have also succumbed to the fatal virus. The 2004 outbreak at the Odzala-Kokoua National Park (Republic of Congo) alone caused a severe decline in the resident western lowland gorilla (Gorilla gorilla gorilla) population, with a 95% mortality rate. Here, we explore the immediate genetic impact of the Ebola outbreak in the western lowland gorilla population. ResultsAssociations with survivorship were evaluated by utilizing DNA obtained from fecal samples from 16 gorilla individuals declared missing after the outbreak (non-survivors) and 15 individuals observed before and after the epidemic (survivors). We used a target enrichment approach to capture the sequences of 123 genes previously associated with immunology and Ebola virus resistance and additionally analyzed the gut microbiome which could influence the survival after an infection. Our results indicate no changes in the population genetic diversity before and after the Ebola outbreak, and no significant differences in microbial community composition between survivors and non-survivors. However, and despite the low power for an association analysis, we do detect six nominally significant missense mutations in four genes that might be candidate variants associated with an increased chance of survival. ConclusionThis study offers the first insight to the genetics of a wild great ape population before and after an Ebola outbreak using target capture experiments from fecal samples, and presents a list of candidate loci that may have facilitated their survival.

genomics↗

bioRxiv2021

HuConTest: Testing human contamination in great ape samples

Modern human contamination is a common problem in ancient DNA studies. We provide evidence that this issue is also present in studies in great apes, which are our closest living relatives, for example in non-invasive samples. Here, we present a simple method to detect human contamination in short read sequencing data from different species. We demonstrate its feasibility using blood and tissue samples from these species. This test is particularly useful for more complex samples (such as museum and non-invasive samples) which have smaller amounts of endogenous DNA, as we show here. Significance statementHuman contamination can be a confounding factor in genomic studies, especially in the case of fecal, museum or ancient DNA from great apes. It is important for quality assessment, screening purposes and prioritization to identify and quantify such contamination. The tool presented here is a simple and versatile method for this purpose, and can be applied to a wide range of sample types.

evolutionary biology↗

bioRxiv2021

Fine-grained temporal mapping of derived high-frequency variants supports the mosaic nature of the evolution of Homo sapiens

As our knowledge about the history of the Homo sapiens lineage becomes increasingly complex, large-scale estimations of the time of emergence of derived variants become essential to be able to offer more precise answers to time-sensitive hypotheses concerning human evolution. Using an open repository of genetic variant age estimations recently made available, we offer here a temporal evaluation of various evolutionarily relevant datasets, such as Homo sapiens-specific variants, high-frequency variants found in genetic windows under positive selection, introgressed variants from extinct human species, as well as putative regulatory variants in various brain regions. We find a recurrent bimodal distribution of high-frequency variants, but also evidence for specific enrichments of gene categories in various time windows, which brings into prominence the 300-500k time slice. We also find evidence for very early mutations impacting the facial phenotype, and much more recent molecular events linked to specific brain regions such as the cerebellum or the precuneus. Additionally, we present a case study of an evolutionarily relevant gene, BAZ1B, and its targets, to emphasize the importance of applying temporal data to specific evolutionary questions. Overall, we present a unique resource that informs and complements our previous knowledge of Homo sapiens evolution using publicly available data, and reinforce the case for the mosaic, temporally very extended nature of the evolutionary trajectory of our species.

evolutionary biology↗

bioRxiv2019

Gene regulatory architectures dissect the evolutionary dynamics of regulatory elements in humans and non-human primates

To gain insight into the evolution of the epigenetic regulation of gene expression in primates, we extensively profiled a new panel of human, chimpanzee, gorilla, orangutan, and macaque lymphoblastoid cell lines (LCLs), using ChIP-seq for five histone marks, ATAC-seq and RNA-seq, further complemented with WGS and WGBS. We annotated regulatory elements and integrated chromatin contact maps to define gene regulatory architectures, creating the largest catalog of regulatory elements in primates to date. We report that epigenetic conservation and its correlation with sequence conservation in primates depends on the activity state of the regulatory element. Our gene regulatory architectures reveal the coordination of different types of components and highlight the role of promoters and intragenic enhancers in the regulation of gene expression. We observed that most regulatory changes occur in weakly active intragenic enhancers. Remarkably, novel human-specific intragenic enhancers with weak activities are enriched in human-specific mutations. These elements appear in genes with signals of positive selection, tissue-specific expression and particular functional enrichments, suggesting that the regulatory evolution of these genes may have contributed to human adaptation.

evolutionary biology↗

bioRxiv2018

Selective single molecule sequencing and assembly of a human Y chromosome of African origin

Mammalian Y chromosomes are often neglected from genomic analysis. Due to their inherent assembly difficulties, high repeat content, and large ampliconic regions1, only a handful of species have their Y chromosome properly characterized. To date, just a single human reference quality Y chromosome, of European ancestry, is available due to a lack of accessible methodology2-5. To facilitate the assembly of such complicated genomic territory, we developed a novel strategy to sequence native, unamplified flow sorted DNA on a MinION nanopore sequencing device. Our approach yields a highly continuous and complete assembly of the first human Y chromosome of African origin. It constitutes a significant improvement over comparable previous methods, increasing continuity by more than 800%6, thus allowing a chromosome scale analysis of human Y chromosomes. Sequencing native DNA also allows to take advantage of the nanopore signal data to detect epigenetic modifications in situ7. This approach is in theory generalizable to any species simplifying the assembly of extremely large and repetitive genomes.

genomics↗

bioRxiv2018

Genetic differences between humans and other hominins contribute to the \"human condition\"

Throughout the past decade, studying ancient genomes provided unique insights into human prehistory, and differences between modern humans and other branches like Neanderthals can enrich our understanding of the molecular basis of unique modern human traits. Modern human variation and the interactions between different hominin lineages are now well studied, making it reasonable to go beyond fixed changes and explore changes that are observed at high frequency in present-day humans. Here, we identify 571 genes with non-synonymous changes at high frequency. We suggest that molecular mechanisms in cell division and networks affecting cellular features of neurons were prominently modified by these changes. Complex phenotypes in brain growth trajectory and cognitive traits are likely influenced by these networks and other changes presented here. We propose that at least some of these changes contributed to uniquely human traits, and should be prioritized for experimental validation.

evolutionary biology↗

bioRxiv2018

Mutations in Pan species are shaped by demographic history and harbor lineage-specific functions

Chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) are the closest living relatives of humans, but they show distinct behavioral and physiological differences, particularly regarding female reproduction. Despite their recent rapid decline, the demographic histories of the two species have been different during the past one to two million years, likely having an impact on their genomic diversity. Here, we analyze the inferred functional consequences of genetic variation across 69 individuals, making use of the most complete dataset of genomic variation in the Pan clade to date. We test to which extent the demographic history influences the efficacy of purifying selection in these species. We find that small historical effective population sizes (Ne) correlate not only with small genetic diversity, but also with more homozygous deleterious alleles, and an increased proportion of deleterious changes at low frequencies. Furthermore, we exploit the catalog of deleterious protein-coding changes on each lineage to investigate the putative genetic basis for phenotypic differences between chimpanzees and bonobos. We show that bonobo-specific non-synonymous changes are enriched in genes related to age at menarche in humans, suggesting that the prominent physiological differences in the female reproductive system between chimpanzees and bonobos might be explained, in part, by putatively adaptive changes on the bonobo lineage.

genomics↗