Preservation of Genetic and Regulatory Robustness in Ancient Gene\ud Duplicates of Saccharomyces cerevisiae

摘要

Biological systems remain unperturbed (are robust) in the face of certain genetic and\udenvironmental challenges. Robustness allows exploration of ecological adaptations. It is unclear\udwhat factors contribute to increasing robustness. Gene duplication has been considered to\udincrease genetic robustness through functional redundancy, accelerating the evolution of novel\udfunctions. However, recent findings have brought the link between duplication and robustness\udinto question. In particular, it remains elusive whether ancient duplicates still bear potential for\udinnovation through preserved redundancy and robustness. Here we have investigated this question\udby evolving the yeast Saccharomyces cerevisiae for 2,200 generations under conditions allowing\udthe accumulation of deleterious mutations and put, for the first time, mechanisms of mutational\udrobustness to test. S. cerevisiae declined in fitness along the evolution experiment but this decline\uddecelerated in later passages suggesting functional compensation of mutated genes. We resequenced\ud28 genomes from experimentally evolved S. cerevisiae lines and found that mutations\udaccumulated more in duplicates than in singletons, and this enrichment of mutations was found\udmainly in genes that originated through small-scale duplications. Genetically interacting\udduplicates showed similar selection signatures and fixed more amino acid replacing mutations\udthan expected. Regulatory robustness of duplicates was supported in our experiment by a larger\udenrichment for mutations at the promoters of duplicates than at those of singletons. Analyses of\udyeast gene expression under different environmental conditions showed larger variation in\udduplicate’s expression than that of singletons under a range of stress conditions, sparking the idea\udthat regulatory robustness allowed exploration of a wider range of phenotypic responses to\udenvironmental stresses, hence faster adaptations. Our data provide strong support for the\udpersistence of genetic and regulatory robustness in ancient duplicates and for the role of this\udrobustness in the evolution of adaptations to various stresses.