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SUMMARY:The mutational process in primate spermatogenesis inferred from Hi
 Fi long read sequencing of testis and sperm samples - Mikkel Heide Schieru
 p\, Aarhus University
DTSTART:20260219T130000Z
DTEND:20260219T140000Z
UID:TALK240229@talks.cam.ac.uk
CONTACT:131500
DESCRIPTION:Eighty per cent of de novo mutations passed on from parents to
  offspring occur in the male germline. We used PacBio HiFi long-read seque
 ncing to identify mutations in testis and sperm samples from nine primate 
 species: human\, chimpanzee\, bonobo\, gorilla\, orangutan\, gibbon\, babo
 on\, macaque\, and marmoset. Based on high-quality scores and auxiliary in
 formation 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 cla
 ssify sequencing reads into cell types based on their CpG methylation patt
 erns\, allowing most testis reads to be classified as either germline or s
 omatic. In human sperm samples\, we find the mutation rate\, mutation spec
 trum and paternal age effect expected from trio studies. In other primate 
 sperm samples\, we find changes to both the spectrum and the rate\, provid
 ing insights into the evolution of germline mutations. The mutational spec
 trum of germline mutations in the testis reflects that of the sperm but re
 veals more non-synonymous changes\, suggesting natural selection against m
 utations in the testis. The somatic mutation rate in the testis is about t
 wice that of the germline. By calling recombination in the same samples\, 
 we identify simple crossovers and gene conversions. The gene conversion tr
 act lengths are short (40-100 bp) across species. However\, we also observ
 e complex gene conversions across all species. We interpret these as resul
 ting from homologous repair before meiosis\, and they typically move sever
 al 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.
LOCATION:Part II Lecture Theatre\, Department of Zoology
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