title: The baker's yeast diploid genome is remarkably stable in vegetative growth and meiosis.
abstract: Accurate estimates of mutation rates provide critical information to analyze genome evolution and organism fitness. We used whole-genome DNA sequencing, pulse-field gel electrophoresis, and comparative genome hybridization to determine mutation rates in diploid vegetative and meiotic mutation accumulation lines of Saccharomyces cerevisiae. The vegetative lines underwent only mitotic divisions while the meiotic lines underwent a meiotic cycle every ∼20 vegetative divisions. Similar base substitution rates were estimated for both lines. Given our experimental design, these measures indicated that the meiotic mutation rate is within the range of being equal to zero to being 55-fold higher than the vegetative rate. Mutations detected in vegetative lines were all heterozygous while those in meiotic lines were homozygous. A quantitative analysis of intra-tetrad mating events in the meiotic lines showed that inter-spore mating is primarily responsible for rapidly fixing mutations to homozygosity as well as for removing mutations. We did not observe 1-2 nt insertion/deletion (in-del) mutations in any of the sequenced lines and only one structural variant in a non-telomeric location was found. However, a large number of structural variations in subtelomeric sequences were seen in both vegetative and meiotic lines that did not affect viability. Our results indicate that the diploid yeast nuclear genome is remarkably stable during the vegetative and meiotic cell cycles and support the hypothesis that peripheral regions of chromosomes are more dynamic than gene-rich central sections where structural rearrangements could be deleterious. This work also provides an improved estimate for the mutational load carried by diploid organisms.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
authors.forename: K T
authors.initials: KT
authors.lastname: Nishant
authors.forename: Wu
authors.initials: W
authors.lastname: Wei
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mancera
authors.forename: Juan Lucas
authors.initials: JL
authors.lastname: Argueso
authors.forename: Andreas
authors.initials: A
authors.lastname: Schlattl
authors.forename: Nicolas
authors.initials: N
authors.lastname: Delhomme
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Bustamante
authors.forename: Jan O
authors.initials: JO
authors.lastname: Korbel
authors.forename: Zhenglong
authors.initials: Z
authors.lastname: Gu
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
authors.forename: Eric
authors.initials: E
authors.lastname: Alani
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D015825:Chromosomes, Fungal / Q000235:genetics; D003198:Computer Simulation; D004271:DNA, Fungal / Q000235:genetics; D004171:Diploidy; D016521:Electrophoresis, Gel, Pulsed-Field; D016681:Genome, Fungal / Q000235:genetics*; D006720:Homozygote; D054643:INDEL Mutation / Q000235:genetics; D007621:Karyotyping; D008540:Meiosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D012098:Reproduction / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000254:growth & development*; D017422:Sequence Analysis, DNA; D013172:Spores, Fungal / Q000166:cytology / Q000235:genetics
chemical_list: D004271:DNA, Fungal