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Transcriptional and mutational signatures of the aging germline

View ORCID ProfileEvan Witt, View ORCID ProfileChristopher B Langer, View ORCID ProfileNicolas Svetec, View ORCID ProfileLi Zhao
doi: https://doi.org/10.1101/2021.11.22.469565
Evan Witt
1Laboratory of Evolutionary Genetics and Genomics, The Rockefeller University, New York, NY 10065, USA
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Christopher B Langer
1Laboratory of Evolutionary Genetics and Genomics, The Rockefeller University, New York, NY 10065, USA
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Nicolas Svetec
1Laboratory of Evolutionary Genetics and Genomics, The Rockefeller University, New York, NY 10065, USA
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Li Zhao
1Laboratory of Evolutionary Genetics and Genomics, The Rockefeller University, New York, NY 10065, USA
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  • For correspondence: lzhao@rockefeller.edu
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Abstract

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 Statement

The authors have declared no competing interest.

Footnotes

  • New data are added. All the analyses are updated.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted August 04, 2022.
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Transcriptional and mutational signatures of the aging germline
Evan Witt, Christopher B Langer, Nicolas Svetec, Li Zhao
bioRxiv 2021.11.22.469565; doi: https://doi.org/10.1101/2021.11.22.469565
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Transcriptional and mutational signatures of the aging germline
Evan Witt, Christopher B Langer, Nicolas Svetec, Li Zhao
bioRxiv 2021.11.22.469565; doi: https://doi.org/10.1101/2021.11.22.469565

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