RT Journal Article
SR Electronic
T1 Transcriptional and mutational signatures of the aging germline
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.22.469565
DO 10.1101/2021.11.22.469565
A1 Evan Witt
A1 Christopher B Langer
A1 Nicolas Svetec
A1 Li Zhao
YR 2022
UL http://biorxiv.org/content/early/2022/08/04/2021.11.22.469565.abstract
AB Aging is a complex biological process that is accompanied by changes in gene expression and mutational load. In many species, including humans, older fathers pass on more paternally-derived de novo mutations; however, the cellular basis and cell types driving this pattern are still unclear. To explore the root causes of this phenomenon, we performed single-cell RNA-sequencing (scRNA-seq) on testes from young and old male Drosophila, as well as genomic sequencing (DNA-seq) on somatic tissues from the same flies. We found that early germ cells from old and young flies enter spermatogenesis with similar mutational loads, but older flies are less able to remove mutations during spermatogenesis. Mutations in old cells may also increase during spermatogenesis. Our data reveal that old and young flies have distinct mutational biases. Many classes of genes show increased post-meiotic expression in the germlines of older flies. Late spermatogenesis-enriched genes have higher dN/dS than early spermatogenesis-enriched genes, supporting the hypothesis that late spermatogenesis is a source of evolutionary innovation. Surprisingly, young fly enriched genes show higher dN/dS than old fly enriched genes. Our results provide novel insights into the role of the germline in de novo mutation.Competing Interest StatementThe authors have declared no competing interest.