Evolutionary Repair: Changes in the Genome Allow Meiotic Cohesin to Support Mitosis

Abstract

Proteins in the same protein family share conserved domains but often perform distinct cellular functions. It remains unclear to what extent the specialized function of a protein is determined by changes in its intrinsic biochemical activity or change in the proteins that interact with it. To probe this question, we studied how kleisin, a subunit of the cohesin complex, evolves to alter its function. In the eukaryotes, mitotic and meiotic kleisins have diverged to accomplish the different patterns of chromosome segregation in mitosis and meiosis. We showed that the budding yeast, Saccharomyces cerevisiae, can use the meiotic kleisin to support mitosis through experimental evolution. Forcing yeast cells to depend on meiotic kleisin, Rec8, in mitosis reduced cellular fitness by 80% due to reduced cohesion between sister chromatids. After 1750 generations of experimental evolution, all the evolved populations increased fitness 50-80% relative to the ancestral Rec8-expressing strain. Comparing the ancestral and evolved genomes shows that Rec8 was not mutated. Instead, adaptive mutations are mainly in genes in the transcriptional mediator complex and cohesin- and cell cycle-related genes. Each beneficial mutation improves the cohesin function of Rec8 in mitosis via slowing down genome replication. This work reveals an unknown functional linkage between genome replication and cohesin function. Overall, this result suggests that changes in proteins that a kleisin protein directly or indirectly interacts with are sufficient for diversifying the cellular function of kleisin.