Low Genetic Quality Alters Key Dimensions of the Mutational Spectrum.

Abstract:

:Mutations affect individual health, population persistence, adaptation, diversification, and genome evolution. There is evidence that the mutation rate varies among genotypes, but the causes of this variation are poorly understood. Here, we link differences in genetic quality with variation in spontaneous mutation in a Drosophila mutation accumulation experiment. We find that chromosomes maintained in low-quality genetic backgrounds experience a higher rate of indel mutation and a lower rate of gene conversion in a manner consistent with condition-based differences in the mechanisms used to repair DNA double strand breaks. These aspects of the mutational spectrum were also associated with body mass, suggesting that the effect of genetic quality on DNA repair was mediated by overall condition, and providing a mechanistic explanation for the differences in mutational fitness decline among these genotypes. The rate and spectrum of substitutions was unaffected by genetic quality, but we find variation in the probability of substitutions and indels with respect to several aspects of local sequence context, particularly GC content, with implications for models of molecular evolution and genome scans for signs of selection. Our finding that the chances of mutation depend on genetic context and overall condition has important implications for how sequences evolve, the risk of extinction, and human health.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Sharp NP,Agrawal AF

doi

10.1371/journal.pbio.1002419

subject

Has Abstract

pub_date

2016-03-25 00:00:00

pages

e1002419

issue

3

eissn

1544-9173

issn

1545-7885

pii

PBIOLOGY-D-15-03259

journal_volume

14

pub_type

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