Loss of heterozygosity results in rapid but variable genome homogenization across genetic backgrounds in yeast

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Abstract

The dynamics and diversity of the appearance of genetic variants play an essential role in the evolution of the genome and the shaping of biodiversity. Recent population-wide genome sequencing surveys have highlighted the importance of loss-of-heterozygosity (LOH) events and have shown that they are a neglected part of the genetic diversity landscape. To assess the extent, variability, and spectrum, we explored the accumulation of LOH events in 169 heterozygous diploid Saccharomyces cerevisiae mutation accumulation lines across nine genetic backgrounds. In total, we detected a large set of 22,828 LOH events across distinct genetic backgrounds with a heterozygous level ranging from 0.1 to 1%. LOH events are very frequent with a rate consistently much higher than the mutation rate, showing their importance for genome evolution. We observed that the interstitial LOH (I-LOH) events, resulting in internal short LOH tracts, were much frequent (n = 19,660) than the terminal LOH (T-LOH) events, i.e., tracts extending to the end of the chromosome (n = 3,168). However, the spectrum, the rate, and the fraction of the genome under LOH vary across genetic backgrounds. Interestingly, we observed that the more the ancestors were heterozygous, the more they accumulated T-LOH events. In addition, frequent short I-LOH tracts are a signature of the lines derived from hybrids with low spore fertility. Finally, we found lines showing almost complete homozygotization during vegetative progression. Overall, our results highlight that the variable dynamics of the LOH accumulation across distinct genetic backgrounds might lead to rapid differential genome evolution during vegetative growth.

Data availability

Sequence data are available from National Centre for Biotechnology Information Sequence Read Archive under accession number: PRJEB43186.

The following data sets were generated

(2021) Sequencing data from 169 S. cerevisiae mutation accumulation lines
PRJEB43186.

https://www.ncbi.nlm.nih.gov/sra/?term=PRJEB43186

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Abhishek Dutta

Université de Strasbourg, Strasbourg, France

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2256-6956
Fabien Dutreux

Université de Strasbourg, Strasbourg, France

Competing interests
The authors declare that no competing interests exist.
Joseph Schacherer

Department of Genetics, Genomics and Microbiology, Université de Strasbourg, CNRS, Strasbourg, France

For correspondence
schacherer@unistra.fr

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6606-6884

Funding

European Research Council (772505)

Joseph Schacherer

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.