Higher-fitness yeast genotypes are less robust to deleterious mutations

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Science  25 Oct 2019:
Vol. 366, Issue 6464, pp. 490-493
DOI: 10.1126/science.aay4199

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Genetic background affects variation

Robustness, or the effect of mutations on fitness, can affect the evolutionary trajectory of a species. By introducing a large number of deleterious mutations into many different genetic backgrounds of yeast, Johnson et al. found that, for many mutations, the more fit the background, the larger the deleterious effect of the mutation (see the Perspective by Miller). A more-fit lineage is thus less tolerant to deleterious mutations, whereas less-fit lineages can tolerate more mutations. This observation supports a tendency toward diminishing returns for beneficial mutations, which has been shown to influence patterns of adaptation.

Science, this issue p. 490; see also p. 418


Natural selection drives populations toward higher fitness, but second-order selection for adaptability and mutational robustness can also influence evolution. In many microbial systems, diminishing-returns epistasis contributes to a tendency for more-fit genotypes to be less adaptable, but no analogous patterns for robustness are known. To understand how robustness varies across genotypes, we measure the fitness effects of hundreds of individual insertion mutations in a panel of yeast strains. We find that more-fit strains are less robust: They have distributions of fitness effects with lower mean and higher variance. These differences arise because many mutations have more strongly deleterious effects in faster-growing strains. This negative correlation between fitness and robustness implies that second-order selection for robustness will tend to conflict with first-order selection for fitness.

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