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Genome-wide mapping of spontaneous genetic alterations in diploid yeast cells.

Publication ,  Journal Article
Sui, Y; Qi, L; Wu, J-K; Wen, X-P; Tang, X-X; Ma, Z-J; Wu, X-C; Zhang, K; Kokoska, RJ; Zheng, D-Q; Petes, TD
Published in: Proc Natl Acad Sci U S A
November 10, 2020

Genomic alterations including single-base mutations, deletions and duplications, translocations, mitotic recombination events, and chromosome aneuploidy generate genetic diversity. We examined the rates of all of these genetic changes in a diploid strain of Saccharomyces cerevisiae by whole-genome sequencing of many independent isolates (n = 93) subcloned about 100 times in unstressed growth conditions. The most common alterations were point mutations and small (<100 bp) insertion/deletions (n = 1,337) and mitotic recombination events (n = 1,215). The diploid cells of most eukaryotes are heterozygous for many single-nucleotide polymorphisms (SNPs). During mitotic cell divisions, recombination can produce derivatives of these cells that have become homozygous for the polymorphisms, termed loss-of-heterozygosity (LOH) events. LOH events can change the phenotype of the cells and contribute to tumor formation in humans. We observed two types of LOH events: interstitial events (conversions) resulting in a short LOH tract (usually less than 15 kb) and terminal events (mostly cross-overs) in which the LOH tract extends to the end of the chromosome. These two types of LOH events had different distributions, suggesting that they may have initiated by different mechanisms. Based on our results, we present a method of calculating the probability of an LOH event for individual SNPs located throughout the genome. We also identified several hotspots for chromosomal rearrangements (large deletions and duplications). Our results provide insights into the relative importance of different types of genetic alterations produced during vegetative growth.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 10, 2020

Volume

117

Issue

45

Start / End Page

28191 / 28200

Location

United States

Related Subject Headings

  • Saccharomyces cerevisiae
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Mutation
  • Loss of Heterozygosity
  • Gene Rearrangement
  • Gene Conversion
  • Diploidy
  • Chromosomes, Fungal
  • Chromosome Mapping
 

Citation

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Sui, Y., Qi, L., Wu, J.-K., Wen, X.-P., Tang, X.-X., Ma, Z.-J., … Petes, T. D. (2020). Genome-wide mapping of spontaneous genetic alterations in diploid yeast cells. Proc Natl Acad Sci U S A, 117(45), 28191–28200. https://doi.org/10.1073/pnas.2018633117
Sui, Yang, Lei Qi, Jian-Kun Wu, Xue-Ping Wen, Xing-Xing Tang, Zhong-Jun Ma, Xue-Chang Wu, et al. “Genome-wide mapping of spontaneous genetic alterations in diploid yeast cells.Proc Natl Acad Sci U S A 117, no. 45 (November 10, 2020): 28191–200. https://doi.org/10.1073/pnas.2018633117.
Sui Y, Qi L, Wu J-K, Wen X-P, Tang X-X, Ma Z-J, et al. Genome-wide mapping of spontaneous genetic alterations in diploid yeast cells. Proc Natl Acad Sci U S A. 2020 Nov 10;117(45):28191–200.
Sui, Yang, et al. “Genome-wide mapping of spontaneous genetic alterations in diploid yeast cells.Proc Natl Acad Sci U S A, vol. 117, no. 45, Nov. 2020, pp. 28191–200. Pubmed, doi:10.1073/pnas.2018633117.
Sui Y, Qi L, Wu J-K, Wen X-P, Tang X-X, Ma Z-J, Wu X-C, Zhang K, Kokoska RJ, Zheng D-Q, Petes TD. Genome-wide mapping of spontaneous genetic alterations in diploid yeast cells. Proc Natl Acad Sci U S A. 2020 Nov 10;117(45):28191–28200.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 10, 2020

Volume

117

Issue

45

Start / End Page

28191 / 28200

Location

United States

Related Subject Headings

  • Saccharomyces cerevisiae
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Mutation
  • Loss of Heterozygosity
  • Gene Rearrangement
  • Gene Conversion
  • Diploidy
  • Chromosomes, Fungal
  • Chromosome Mapping