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Germline mutation rate is elevated in young and old parents in Caenorhabditis remanei

Chen, Hwei Yen LU ; Krieg, Therese ; Mautz, Brian ; Jolly, Cécile ; Scofield, Douglas ; Maklakov, Alexei A. and Immler, Simone (2023) In Evolution letters 7(6). p.478-489
Abstract

The effect of parental age on germline mutation rate across generations is not fully understood. While some studies report a positive linear relationship of mutation rate with increasing age, others suggest that mutation rate varies with age but not in a linear fashion. We investigated the effect of parental age on germline mutations by generating replicated mutation accumulation lines in Caenorhabditis remanei at three parental ages ("Young T1"[Day 1], "Peak T2"[Day 2], and "Old T5"[Day 5] parents). We conducted whole-genome resequencing and variant calling to compare differences in mutation rates after three generations of mutation accumulation. We found that Peak T2 lines had an overall reduced mutation rate compared to Young T1 and... (More)

The effect of parental age on germline mutation rate across generations is not fully understood. While some studies report a positive linear relationship of mutation rate with increasing age, others suggest that mutation rate varies with age but not in a linear fashion. We investigated the effect of parental age on germline mutations by generating replicated mutation accumulation lines in Caenorhabditis remanei at three parental ages ("Young T1"[Day 1], "Peak T2"[Day 2], and "Old T5"[Day 5] parents). We conducted whole-genome resequencing and variant calling to compare differences in mutation rates after three generations of mutation accumulation. We found that Peak T2 lines had an overall reduced mutation rate compared to Young T1 and Old T5 lines, but this pattern of the effect varied depending on the variant impact. Specifically, we found no high-impact variants in Peak T2 lines, and modifiers and up- and downstream gene variants were less frequent in these lines. These results suggest that animals at the peak of reproduction have better DNA maintenance and repair compared to young and old animals. We propose that C. remanei start to reproduce before they optimize their DNA maintenance and repair, trading the benefits of earlier onset of reproduction against offspring mutation load. The increase in offspring mutation load with age likely represents germline senescence.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
age-related mutation rate, germline mutations, mutation accumulation, parental age effects, selection shadow, SNPs
in
Evolution letters
volume
7
issue
6
pages
12 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:38045724
  • scopus:85180334091
ISSN
2056-3744
DOI
10.1093/evlett/qrad052
language
English
LU publication?
yes
id
ef9a5e66-582f-4cf7-9c99-39f9a5899f80
date added to LUP
2024-01-03 12:06:48
date last changed
2024-04-18 09:27:02
@article{ef9a5e66-582f-4cf7-9c99-39f9a5899f80,
  abstract     = {{<p>The effect of parental age on germline mutation rate across generations is not fully understood. While some studies report a positive linear relationship of mutation rate with increasing age, others suggest that mutation rate varies with age but not in a linear fashion. We investigated the effect of parental age on germline mutations by generating replicated mutation accumulation lines in Caenorhabditis remanei at three parental ages ("Young T1"[Day 1], "Peak T2"[Day 2], and "Old T5"[Day 5] parents). We conducted whole-genome resequencing and variant calling to compare differences in mutation rates after three generations of mutation accumulation. We found that Peak T2 lines had an overall reduced mutation rate compared to Young T1 and Old T5 lines, but this pattern of the effect varied depending on the variant impact. Specifically, we found no high-impact variants in Peak T2 lines, and modifiers and up- and downstream gene variants were less frequent in these lines. These results suggest that animals at the peak of reproduction have better DNA maintenance and repair compared to young and old animals. We propose that C. remanei start to reproduce before they optimize their DNA maintenance and repair, trading the benefits of earlier onset of reproduction against offspring mutation load. The increase in offspring mutation load with age likely represents germline senescence.</p>}},
  author       = {{Chen, Hwei Yen and Krieg, Therese and Mautz, Brian and Jolly, Cécile and Scofield, Douglas and Maklakov, Alexei A. and Immler, Simone}},
  issn         = {{2056-3744}},
  keywords     = {{age-related mutation rate; germline mutations; mutation accumulation; parental age effects; selection shadow; SNPs}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{478--489}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Evolution letters}},
  title        = {{Germline mutation rate is elevated in young and old parents in Caenorhabditis remanei}},
  url          = {{http://dx.doi.org/10.1093/evlett/qrad052}},
  doi          = {{10.1093/evlett/qrad052}},
  volume       = {{7}},
  year         = {{2023}},
}