Elevated mutation in haploid yeast driven by translesion synthesis

Area of Science:

• Evolutionary biology
• Molecular genetics
• Yeast genetics

Background:

• Mutation patterns are influenced by selection and genetic drift, but their relative impacts remain unclear.
• Haploid *Saccharomyces cerevisiae* cells show higher mutation rates than diploid cells, potentially due to limited selection acting on this cell type.
• Elevated mutation in haploid genomes occurs in late-replicating regions, suggesting involvement of error-prone translesion synthesis (TLS) repair.

Purpose of the Study:

• To investigate if the preferential use of TLS by haploids explains genome-wide mutation pattern differences between haploid and diploid yeast.
• To determine the role of the *REV1* gene in differential mutation rates between yeast cell types.

Main Methods:

• Mutation accumulation experiments were conducted in both haploid and diploid *Saccharomyces cerevisiae*.
• The *REV1* gene, essential for initiating TLS, was deleted in both cell types (*rev1*Δ strains).
• Single nucleotide mutation rates were estimated and compared between wild-type and *rev1*Δ haploid and diploid strains.

Main Results:

• Wild-type haploid yeast exhibited a 50% higher single nucleotide mutation rate compared to wild-type diploid yeast.
• Deletion of *REV1* eliminated this difference, causing mutation rates in haploid and diploid *rev1*Δ strains to converge.
• The *REV1* gene was found to be crucial for mitochondrial genome maintenance in both yeast cell types.

Conclusions:

• The mutagenic impact of translesion synthesis (TLS) is significantly stronger in haploid yeast, likely due to limited selection opportunities.
• Differential reliance on TLS contributes to distinct genome-wide mutation patterns observed between haploid and diploid yeast.
• *REV1* plays a significant role in maintaining the integrity of both nuclear and mitochondrial genomes in *Saccharomyces cerevisiae*.