The many faces of an aging germline: reduced germline mutation rate at reproductive peak
(2024) Diversity and Evolution in Cell Biology- Abstract
- Germline mutations are the ultimate source of genetic diversity, and germline mutation rate is central to evolutionary biology. However, while germline mutations primarily arise during DNA replication in the parental germline and should accumulate with increasing parental age, studies showed that germline mutation rate does not necessarily track germ cell divisions. This suggests that germline mutation rate is subjected to selection and the relationship between germline mutation rate and parental age is likely to be non-linear. To precisely characterize parental age effect, we measured germline mutation rate in a short-lived worm, Caenorhabditis remanei, using mutation accumulation, and in a long-lived ant, Acromyrmex echinatior, using a... (More)
- Germline mutations are the ultimate source of genetic diversity, and germline mutation rate is central to evolutionary biology. However, while germline mutations primarily arise during DNA replication in the parental germline and should accumulate with increasing parental age, studies showed that germline mutation rate does not necessarily track germ cell divisions. This suggests that germline mutation rate is subjected to selection and the relationship between germline mutation rate and parental age is likely to be non-linear. To precisely characterize parental age effect, we measured germline mutation rate in a short-lived worm, Caenorhabditis remanei, using mutation accumulation, and in a long-lived ant, Acromyrmex echinatior, using a pedigree-based approach. In both systems, germline mutation rate was measured at young, prime (reproductive peak), and old parental ages.
Specifically, in worms, eighteen replicated mutation accumulation lines were derived from an inbred strain, thus all lines shared an initially identical genetic background. To characterize parental age effect on germline mutation rate, lines were propagated at day 1 (Young T1), day 2 (Peak T2), and day 5 (Old T5) postsexual maturity. As worms have a short lifespan of c.a. 2 weeks and reach reproductive peak around day 2 of adulthood, these parental age regimes covered the ages before (Young T1), during (Peak T2), after (Old T5) the reproductive peak of the ancestral inbred lines. All lines were propagated by randomly selecting one virgin male and one virgin female (full siblings) at each generation and allowing them to reproduce. We took advantage of the fact that all lines were direct descendants of two progenitors and reasoned that 1) the genotype shared across lines was the ‘ancestral’ genotype, and 2) unique SNPs discovered in only one line that were different from the allele shared by the other lines were line-specific germline mutations that occurred during the mutation accumulation process.
In the ant system, maternal age effect can be assessed by comparing the genomes of the mother queen and her sons, for males develop from unfertilized haploid eggs and germline mutations in males are always maternally inherited. Maternal age effect on germline mutation rate was assessed using a pedigree-based, longitudinal dataset of mother-son sequences. We whole-genome re-sequenced a total of 87 sons and their mother queens from three colonies (each colony represents a pedigree). The maternal ages sampled ranged from the young, incipient stage (0-5 years), the ergonomic and reproductive stage (5-15 years), to old ages (>15 years). For each pedigree, we identified germline mutations in each son as SNPs that did not exist in the genome of his mother queen. We then calculated germline mutation rate across maternal ages within each pedigree.
In both systems, we showed that germline mutation rate does not increase linearly with parental age, and prime parental age had a reduced germline mutation rate compared to young and old ages. The non-linear function of offspring germline mutation load and parental age likely represents selection against germline senescence at reproductive peak.
(Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/030716ee-d114-4043-9c96-07ddb43c4656
- author
- Chen, Hwei-Yen LU
- organization
- publishing date
- 2024-06-24
- type
- Contribution to conference
- publication status
- unpublished
- subject
- conference name
- Diversity and Evolution in Cell Biology
- conference location
- Spain
- conference dates
- 2024-06-24 - 2024-06-27
- language
- English
- LU publication?
- yes
- id
- 030716ee-d114-4043-9c96-07ddb43c4656
- date added to LUP
- 2025-02-03 09:34:25
- date last changed
- 2025-04-04 13:55:51
@misc{030716ee-d114-4043-9c96-07ddb43c4656,
abstract = {{Germline mutations are the ultimate source of genetic diversity, and germline mutation rate is central to evolutionary biology. However, while germline mutations primarily arise during DNA replication in the parental germline and should accumulate with increasing parental age, studies showed that germline mutation rate does not necessarily track germ cell divisions. This suggests that germline mutation rate is subjected to selection and the relationship between germline mutation rate and parental age is likely to be non-linear. To precisely characterize parental age effect, we measured germline mutation rate in a short-lived worm, Caenorhabditis remanei, using mutation accumulation, and in a long-lived ant, Acromyrmex echinatior, using a pedigree-based approach. In both systems, germline mutation rate was measured at young, prime (reproductive peak), and old parental ages. <br/><br/>Specifically, in worms, eighteen replicated mutation accumulation lines were derived from an inbred strain, thus all lines shared an initially identical genetic background. To characterize parental age effect on germline mutation rate, lines were propagated at day 1 (Young T1), day 2 (Peak T2), and day 5 (Old T5) postsexual maturity. As worms have a short lifespan of c.a. 2 weeks and reach reproductive peak around day 2 of adulthood, these parental age regimes covered the ages before (Young T1), during (Peak T2), after (Old T5) the reproductive peak of the ancestral inbred lines. All lines were propagated by randomly selecting one virgin male and one virgin female (full siblings) at each generation and allowing them to reproduce. We took advantage of the fact that all lines were direct descendants of two progenitors and reasoned that 1) the genotype shared across lines was the ‘ancestral’ genotype, and 2) unique SNPs discovered in only one line that were different from the allele shared by the other lines were line-specific germline mutations that occurred during the mutation accumulation process.<br/><br/><br/>In the ant system, maternal age effect can be assessed by comparing the genomes of the mother queen and her sons, for males develop from unfertilized haploid eggs and germline mutations in males are always maternally inherited. Maternal age effect on germline mutation rate was assessed using a pedigree-based, longitudinal dataset of mother-son sequences. We whole-genome re-sequenced a total of 87 sons and their mother queens from three colonies (each colony represents a pedigree). The maternal ages sampled ranged from the young, incipient stage (0-5 years), the ergonomic and reproductive stage (5-15 years), to old ages (>15 years). For each pedigree, we identified germline mutations in each son as SNPs that did not exist in the genome of his mother queen. We then calculated germline mutation rate across maternal ages within each pedigree.<br/><br/>In both systems, we showed that germline mutation rate does not increase linearly with parental age, and prime parental age had a reduced germline mutation rate compared to young and old ages. The non-linear function of offspring germline mutation load and parental age likely represents selection against germline senescence at reproductive peak.<br/><br/>}},
author = {{Chen, Hwei-Yen}},
language = {{eng}},
month = {{06}},
title = {{The many faces of an aging germline: reduced germline mutation rate at reproductive peak}},
year = {{2024}},
}