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

PLoS Biol. 2020 Mar 10;18(3):e3000635. doi: 10.1371/journal.pbio.3000635. eCollection 2020 Mar.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Biological / genetics
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomes, Fungal / genetics
  • Chromosomes, Fungal / metabolism*
  • Cohesins
  • Directed Molecular Evolution
  • Evolution, Molecular
  • Genome, Fungal
  • Meiosis
  • Mitosis*
  • Mutation
  • Replication Origin
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sister Chromatid Exchange

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • MCD1 protein, S cerevisiae
  • REC8 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins