Abstract
Author SummaryWhile core cellular processes are generally conserved during evolution, the constituent genes differ somewhat between related species with similar lifestyles. Why should this be so? In this work, we propose that gene loss may initially be deleterious, but organisms can recover fitness by the accumulation of compensatory mutations elsewhere in the genome. To investigate this process in the laboratory, we investigated 180 haploid yeast strains, each of which initially displayed slow growth owing to the deletion of a single gene. Laboratory evolutionary experiments revealed that defects in a broad range of molecular processes can readily be compensated during evolution. Genomic analyses and functional assays demonstrated that compensatory evolution generates hidden genetic and physiological variation across parallel evolving lines, which can be revealed when the environment changes. Strikingly, despite nearly full recovery of fitness, the wild-type genomic expression pattern is generally not restored. Based on these results, we argue that genomes undergo major changes not simply to adapt to external conditions but also to compensate for previously accumulated deleterious mutations.
Highlights
Deleterious, but non-lethal mutations are constantly generated and can hitchhike with adaptive mutations [1]
While core cellular processes are generally conserved during evolution, the constituent genes differ somewhat between related species with similar lifestyles. Why should this be so? In this work, we propose that gene loss may initially be deleterious, but organisms can recover fitness by the accumulation of compensatory mutations elsewhere in the genome
To investigate this process in the laboratory, we investigated 180 haploid yeast strains, each of which initially displayed slow growth owing to the deletion of a single gene
Summary
Deleterious, but non-lethal mutations are constantly generated and can hitchhike with adaptive mutations [1]. Such deleterious alleles are widespread in eukaryotic populations [2,3]. Theoretical works suggest that mutant subpopulations can cross fitness valleys by the simultaneous fixation of a compensatory mutation in the population [4,5]. This process can work in large populations and is facilitated by linkage of the two alleles [5]
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