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.

Highlights

  • Genetic diversity relies on diversification of the parental genome information

  • The genetic diversity of eukaryotes relies on the diversification of the parental information, mostly occurring by recombination during gamete formation

  • We sequenced the genome of S. cerevisiae hybrid diploid cells that enter the processes of meiosis and Return To mitotic Growth (RTG)

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Summary

Introduction

Genetic diversity relies on diversification of the parental genome information. Besides spontaneous and environmentally induced de novo mutations, sexual reproduction is the prominent source of genetic diversity: it reshuffles the genetic information among individuals from a given species, creating the new combinations of alleles upon which the Darwinian selection will potentially act. The meiotic developmental program involves the segregation of the homologous pairs of sister chromatids to opposite poles at the first meiotic division (Meiosis-I or reductional division), followed by the segregation of the sister chromatids at the second meiotic division (Meiosis-II or equational division), which is followed by the differentiation of gametes, or spores in yeast (Fig 1)[1]. Another hallmark of meiosis is the high level of inter-homologs recombination during the prophase-I of meiosis. The frequent spontaneous formation of disomic chromosome 21 gametes in the male or female gametogenesis is the cause of Down syndrome in humans [6]

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