Environment-independent distribution of mutational effects emerges from microscopic epistasis

• 成果类型: Article
• 署名作者: Ardell, Sarah M.; Martsul, Alena; Johnson, Milo S.; Kryazhimskiy, Sergey
• 署名单位: University of California System; University of California San Diego; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Illumina
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9772
• DOI: 10.1126/science.adn0753
• 发表日期: 2024-10-04
• 页码: 87-92
• 关键词: diminishing-returns epistasis; beneficial mutations; escherichia-coli; adaptation; selection; tolerance; EVOLUTION; stress

摘要

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 similar to 100 insertion mutations in 42 strains of Saccharomyces cerevisiae in six laboratory environments and found that the global epistasis scaling is nearly invariant across environments. Instead, the environment tunes one global parameter, the background fitness at which most mutations switch sign. As a consequence, the distribution of mutational effects is predictable across genotypes and environments. Our results suggest that the effective dimensionality of genotype-to-phenotype maps across environments is surprisingly low.