Extensive Recombination of a Yeast Diploid Hybrid through Meiotic Reversion

PLoS Genet. 2016 Feb 1;12(2):e1005781. doi: 10.1371/journal.pgen.1005781. eCollection 2016 Feb.

Abstract

In somatic cells, recombination between the homologous chromosomes followed by equational segregation leads to loss of heterozygosity events (LOH), allowing the expression of recessive alleles and the production of novel allele combinations that are potentially beneficial upon Darwinian selection. However, inter-homolog recombination in somatic cells is rare, thus reducing potential genetic variation. Here, we explored the property of S. cerevisiae to enter the meiotic developmental program, induce meiotic Spo11-dependent double-strand breaks genome-wide and return to mitotic growth, a process known as Return To Growth (RTG). Whole genome sequencing of 36 RTG strains derived from the hybrid S288c/SK1 diploid strain demonstrates that the RTGs are bona fide diploids with mosaic recombined genome, derived from either parental origin. Individual RTG genome-wide genotypes are comprised of 5 to 87 homozygous regions due to the loss of heterozygous (LOH) events of various lengths, varying between a few nucleotides up to several hundred kilobases. Furthermore, we show that reiteration of the RTG process shows incremental increases of homozygosity. Phenotype/genotype analysis of the RTG strains for the auxotrophic and arsenate resistance traits validates the potential of this procedure of genome diversification to rapidly map complex traits loci (QTLs) in diploid strains without undergoing sexual reproduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Separation
  • Chromosome Mapping
  • Crossing Over, Genetic
  • Diploidy*
  • Gene Conversion / genetics
  • Genetic Variation
  • Genome, Fungal
  • Haplotypes / genetics
  • Homozygote
  • Hybridization, Genetic*
  • Meiosis / genetics*
  • Phenotype
  • Quantitative Trait Loci / genetics
  • Recombination, Genetic*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / genetics*

Grant support

High-throughput sequencing has been performed by the ICGex NGS platform of the Institut Curie supported by the grants ANR-10-EQPX-03 (Equipex) and ANR-10-INBS-09-08 (France Génomique Consortium) from the Agence Nationale de le Recherche ("Investissements d'Avenir" program) and by the Canceropole Ile-de-France. AN research is supported by grant ANR13-BSV6-0006-02. RL received fellowships from the Ministère de l’Enseignement Supérieur et de la Recherche (MESR) and from the Association pour la Recherche sur le Cancer (ARC). GL research is supported by grant ATIP-Avenir (CNRS/INSERM), FP7- PEOPLE-2012-CIG (322035), ANR (ANR-13-BSV6-0006-01; ANR-11-LABX-0028-01), ARC (SFI20111203947) and Dupont Young Professor Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.