It is widely accepted that mutations occur randomly regardless of their effects. Under this principle, observed variation along the genome reflects selection acting on random mutations. Writing in Nature in January 2022, Monroe et al. show evidence for natural selection acting directly on mutation rates in the plant Arabidopsis thaliana. The authors analysed several genetic datasets (including mutation accumulation lines and a global set of Arabidopsis accessions) and found associations between mutation frequencies and several features of the genome, including epigenomics, gene structure and function. For example, mutation rates were lower within gene bodies than in intergenic regions and higher in genes that lack introns. Essential genes, such as those involved in translation, had lower mutation rates when compared to genes with an environment-related function, such as response to stress — these differences in mutation rate are probably associated with epigenomic features. The authors then relate differences in mutation frequencies to evolutionary constraint, and show that genes that are subject to purifying selection tend to stay in epigenomic states associated with a low mutation rate and do indeed have lower mutation rates. Altogether, the authors suggest that the observed bias towards a reduced mutation rate in specific regions of the Arabidopsis genome is adaptive because it reduces deleterious mutations and is mediated by a link between mutation rate and the epigenome.
We selected this paper because of the demonstration of adaptive mutation bias in Arabidopsis. The study challenges the long-standing assumption of evolutionary biology that mutations are random in respect to their effect, and suggests that selection acting on mutation rates may contribute to patterns of genetic variation observed in nature. However, another recent paper (H. Liu & J. Zhang. Mol. Biol. Evol. 39, msac169; 2022) did not find support for bias in mutation rate in yeast and humans. Debate around this topic is bound to continue.
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