Evolutionary repair: Changes in multiple functional modules allow meiotic cohesin to support mitosis

• Published in: PLoS biology Vol. 18; no. 3; p. e3000635
• Main Authors: Hsieh, Yu-Ying Phoebe, Makrantoni, Vasso, Robertson, Daniel, Marston, Adèle L, Murray, Andrew W
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.03.2020; Public Library of Science (PLoS)
• Subjects: Adaptation, Biological - genetics; Biology and Life Sciences; Cell cycle; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Chromosomes; Chromosomes, Fungal - genetics; Chromosomes, Fungal - metabolism; Cohesin; Cohesins; Cohesion; Directed Molecular Evolution; Evolution; Evolution, Molecular; Fitness; Genome, Fungal; Genomes; Genotypes; Kinases; Meiosis; Mitosis; Mutation; Perturbation; Phenotypes; Populations; Proteins; Recombination; Regulators; Replication; Replication Origin; Reproductive fitness; S phase; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Sister Chromatid Exchange; Transcription; Yeast; Yeasts; United Kingdom > UK; United States > US; Massachusetts
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3000635

The role of proteins often changes during evolution, but we do not know how cells adapt when a protein is asked to participate in a different biological function. We forced the budding yeast, Saccharomyces cerevisiae, to use the meiosis-specific kleisin, recombination 8 (Rec8), during the mitotic cell cycle, instead of its paralog, Scc1. This perturbation impairs sister chromosome linkage, advances the timing of genome replication, and reduces reproductive fitness by 45%. We evolved 15 parallel populations for 1,750 generations, substantially increasing their fitness, and analyzed the genotypes and phenotypes of the evolved cells. Only one population contained a mutation in Rec8, but many populations had mutations in the transcriptional mediator complex, cohesin-related genes, and cell cycle regulators that induce S phase. These mutations improve sister chromosome cohesion and delay genome replication in Rec8-expressing cells. We conclude that changes in known and novel partners allow cells to use an existing protein to participate in new biological functions.