Genetic drift, selection and the evolution of the mutation rate

• Published in: Nature reviews. Genetics Vol. 17; no. 11; pp. 704 - 714
• Main Authors: Lynch, Michael, Ackerman, Matthew S., Gout, Jean-Francois, Long, Hongan, Sung, Way, Thomas, W. Kelley, Foster, Patricia L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2016; Nature Publishing Group
• Subjects: 631/181/2474; 631/181/2475; 631/208/191/1908; 631/208/212/2304; 631/208/457/649; 631/208/514/2254; 631/208/737; Agriculture; Animal Genetics and Genomics; Biological Evolution; Biomedicine; Cancer Research; DNA replication; Evolution; Gene Function; Gene mutation; Genetic Drift; Genetic research; Genetic Variation - genetics; Genomes; Human Genetics; Humans; Hypotheses; Microorganisms; Models, Genetic; Mutation; Mutation Rate; Observations; opinion-2; Phylogenetics; Properties; Selection, Genetic - genetics; Transferases
• ISSN: 1471-0056; 1471-0064
• DOI: 10.1038/nrg.2016.104

Mutation is the source of genetic diversity on which natural selection acts, therefore understanding the rates of mutations is crucial for understanding evolutionary trajectories. In this Opinion article, the authors discuss how emerging experimental mutation-rate data from genome-wide sequencing studies, combined with population-genetic theory, can provide unifying explanations for the diversity in mutation rates between species and across genomic locations. As one of the few cellular traits that can be quantified across the tree of life, DNA-replication fidelity provides an excellent platform for understanding fundamental evolutionary processes. Furthermore, because mutation is the ultimate source of all genetic variation, clarifying why mutation rates vary is crucial for understanding all areas of biology. A potentially revealing hypothesis for mutation-rate evolution is that natural selection primarily operates to improve replication fidelity, with the ultimate limits to what can be achieved set by the power of random genetic drift. This drift-barrier hypothesis is consistent with comparative measures of mutation rates, provides a simple explanation for the existence of error-prone polymerases and yields a formal counter-argument to the view that selection fine-tunes gene-specific mutation rates.