Environment-independent distribution of mutational effects emerges from microscopic epistasis.

Predicting how new mutations alter phenotypes is difficult because mutational effects vary across genotypes and environments. Recently discovered global epistasis, in which the fitness effects of mutations scale with the fitness of the background genotype, can improve predictions, but how the environment modulates this scaling is unknown. We measured the fitness effects of ~100 insertion mutations in 42 strains of in six laboratory environments and found that the global epistasis scaling is nearly invariant across environments.

Upper Bound on the Mutational Burden Imposed by a CRISPR-Cas9 Gene-Drive Element.

CRISPR-Cas9 gene drives (CCGDs) are powerful tools for genetic control of wild populations, useful for eradication of disease vectors, conservation of endangered species and other applications. However, Cas9 alone and in a complex with gRNA can cause double-stranded DNA breaks at off-target sites, which could increase the mutational load and lead to loss of heterozygosity (LOH). These undesired effects raise potential concerns about the long-term evolutionary safety of CCGDs, but the magnitude of these effects is unknown.

Environment-independent distribution of mutational effects emerges from microscopic epistasis.

Predicting how new mutations alter phenotypes is difficult because mutational effects vary across genotypes and environments. Recently discovered global epistasis, where the fitness effects of mutations scale with the fitness of the background genotype, can improve predictions, but how the environment modulates this scaling is unknown. We measured the fitness effects of ~100 insertion mutations in 42 strains of in six laboratory environments and found that the global-epistasis scaling is nearly invariant across environments.

Higher-fitness yeast genotypes are less robust to deleterious mutations.

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.