Zoology Department Seminar: The mutational process in primate spermatogenesis inferred from HiFi long read sequencing of testis and sperm samples

Speaker: Prof Mikkel Heide Schierup, Aarhus University

Title: The mutational process in primate spermatogenesis inferred from HiFi long read sequencing of testis and sperm samples

Abstract: Eighty per cent of de novo mutations passed on from parents to offspring occur in the male germline. We used PacBio HiFi long-read sequencing to identify mutations in testis and sperm samples from nine primate species: human, chimpanzee, bonobo, gorilla, orangutan, gibbon, baboon, macaque, and marmoset. Based on high-quality scores and auxiliary information from PacBio sequencing, we can confidently identify mutations, short indels, and evidence for genetic exchange (recombination and gene conversion). Furthermore, we developed a likelihood-based approach to classify sequencing reads into cell types based on their CpG methylation patterns, allowing most testis reads to be classified as either germline or somatic. In human sperm samples, we find the mutation rate, mutation spectrum and paternal age effect expected from trio studies. In other primate sperm samples, we find changes to both the spectrum and the rate, providing insights into the evolution of germline mutations. The mutational spectrum of germline mutations in the testis reflects that of the sperm but reveals more non-synonymous changes, suggesting natural selection against mutations in the testis. The somatic mutation rate in the testis is about twice that of the germline. By calling recombination in the same samples, we identify simple crossovers and gene conversions. The gene conversion tract lengths are short (40-100 bp) across species. However, we also observe complex gene conversions across all species. We interpret these as resulting from homologous repair before meiosis, and they typically move several SNVs between haplotypes over 10 kb. Intersecting recombination calling with de novo mutation calling, we directly observe a mutagenic effect of recombination, with the rate of complex gene conversion higher than that of simple gene conversions and crossovers.

Our Departmental Seminars run weekly on Thursdays during term time. They cover recent research on a wide variety of topics from evolutionary genetics through behavioural ecology to ecology and natural history.  

Everyone in Zoology is invited, and Part II undergraduate zoologists are particularly encouraged to attend.  Please click here for a list of all of this term's seminars.