Department of Ecology, Behavior and Evolution, University of California, San Diego, La Jolla, CA, USA.
Department of Integrative Biology, University of California, Berkeley, Berkeley, CA, USA.
Science. 2024 Oct 4;386(6717):87-92. doi: 10.1126/science.adn0753. Epub 2024 Oct 3.
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. 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.
预测新突变如何改变表型是困难的，因为突变效应在基因型和环境中是不同的。最近发现的全局性上位性（global epistasis），即突变的适应度效应与背景基因型的适应度成比例，可以改善预测，但环境如何调节这种比例尚不清楚。我们在六个实验室环境中测量了 42 株 中的约 100 个插入突变的适应度效应，发现全局性上位性比例在环境中几乎不变。相反，环境调节了一个全局参数，即大多数突变发生符号变化时的背景适应度。因此，突变效应的分布在基因型和环境中是可预测的。我们的结果表明，跨环境的基因型到表型图谱的有效维数出奇地低。
