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Peer-reviewedCC BY-NC-ND 4.0Genetics

Elevated mutation in haploid yeast driven by error-prone Rev1 polymerase

Abstract

The impact of selection vs genetic drift on the evolution of mutation patterns is unclear. In Saccharomyces cerevisiae, which is predominantly diploid in nature, there is evidence that haploid cells have a higher mutation rate than diploids, suggesting that a haploid-specific mutator phenotype may have evolved due to the limited opportunity for selection to act on this rare cell type. Mutation in haploids was primarily elevated in late-replicating regions of the genome, implicating error-prone translesion synthesis (TLS) repair. Additional research has demonstrated that removing REV1, a gene responsible for initiating TLS, causes a reduction in haploid mutation rate. To assess whether the preferential use of this error-prone repair pathway by haploids explains the difference in genome-wide mutation patterns between cell types, we deleted REV1 in both diploid and haploid S. cerevisiae and estimated their mutation rates using a mutation accumulation experiment. Consistent with a previous study, we found a 50% higher single-nucleotide mutation rate in REV1+ haploids than in REV1+ diploids. Deleting the REV1 gene caused this difference to vanish, with mutation rates in haploid and diploid rev1Δ lines converging on 2.4 × 10–10. Our results suggest that the mutagenic effect of TLS is much stronger in haploids, reflecting a limited opportunity for selection to act on mutation rates in rarer cells or smaller populations. We also find evidence that REV1 plays an important role in mitochondrial genome maintenance in both cell types.

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BibTeX
@article{fredetteroman2026elevated,
  title = {{Elevated mutation in haploid yeast driven by error-prone Rev1 polymerase}},
  author = {Jacob Fredette-Roman and Denise R Smith and Sanad B Omari and Nathaniel P Sharp},
  journal = {Genetics},
  year = {2026},
  month = jul,
  doi = {10.1093/genetics/iyag184},
  url = {https://doi.org/10.1093/genetics/iyag184},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Elevated mutation in haploid yeast driven by error-prone Rev1 polymerase
AU  - Jacob Fredette-Roman
AU  - Denise R Smith
AU  - Sanad B Omari
AU  - Nathaniel P Sharp
PY  - 2026
DA  - 2026/07/15
JO  - Genetics
DO  - 10.1093/genetics/iyag184
UR  - https://doi.org/10.1093/genetics/iyag184
AB  - The impact of selection vs genetic drift on the evolution of mutation patterns is unclear. In Saccharomyces cerevisiae, which is predominantly diploid in nature, there is evidence that haploid cells have a higher mutation rate than diploids, suggesting that a haploid-specific mutator phenotype may have evolved due to the limited opportunity for selection to act on this rare cell type. Mutation in haploids was primarily elevated in late-replicating regions of the genome, implicating error-prone translesion synthesis (TLS) repair. Additional research has demonstrated that removing REV1, a gene responsible for initiating TLS, causes a reduction in haploid mutation rate. To assess whether the preferential use of this error-prone repair pathway by haploids explains the difference in genome-wide mutation patterns between cell types, we deleted REV1 in both diploid and haploid S. cerevisiae and estimated their mutation rates using a mutation accumulation experiment. Consistent with a previous study, we found a 50% higher single-nucleotide mutation rate in REV1+ haploids than in REV1+ diploids. Deleting the REV1 gene caused this difference to vanish, with mutation rates in haploid and diploid rev1Δ lines converging on 2.4 × 10–10. Our results suggest that the mutagenic effect of TLS is much stronger in haploids, reflecting a limited opportunity for selection to act on mutation rates in rarer cells or smaller populations. We also find evidence that REV1 plays an important role in mitochondrial genome maintenance in both cell types.
SN  - 0016-6731
SN  - 1943-2631
ER  -