Biology subjects

Kuhlwilm, M.

Publications and source records attributed to Kuhlwilm, M..

3 recordsLinked to original sources

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↗