Stable hypermutators revealed by the genomic landscape of genes involved in genome stability among yeast species
Open accessAbstract
Mutator phenotypes are short-lived due to the rapid accumulation of deleterious mutations. Yet, recent observations reveal that certain fungi can undergo prolonged accelerated evolution after losing genes involved in DNA repair. Here, we surveyed 1,154 yeast genomes representing nearly all known yeast species of the subphylum Saccharomycotina (phylum Ascomycota) to examine the relationship between reduced gene repertoires broadly associated with genome stability functions (eg DNA repair, cell cycle) and elevated evolutionary rates. We identified 3 distantly related lineages-encompassing 12% of species-that had both the most streamlined sets of genes involved in genome stability (specifically DNA repair) and the highest evolutionary rates in the entire subphylum. Two of these "faster-evolving lineages" (FELs)-a subclade within the order Pichiales and the Wickerhamiella/Starmerella (W/S) clade (order Dipodascales)-are described here for the first time, while the third corresponds to a previously documented Hanseniaspora FEL. Examination of genome stability gene repertoires revealed a set of genes predominantly absent in these 3 FELs, suggesting a potential role in the observed acceleration of evolutionary rates. In the W/S clade, genomic signatures are consistent with a substantial mutational burden, including pronounced A|T bias and endogenous DNA damage. Interestingly, we found that the W/S clade also contains DNA repair genes possibly acquired through horizontal gene transfer, including a photolyase of bacterial origin. These findings highlight how hypermutators can persist across macroevolutionary timescales, potentially linked to the loss of genes related to genome stability, with horizontal gene transfer as a possible avenue for partial functional compensation.
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The accelerated gene loss in this clade was recently associated with a mutator phenotype related to impaired DNA repair.
“The accelerated gene loss in this clade was recently associated with a mutator phenotype related to impaired DNA repair (Gonçalves et al. 2025).”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Gonçalves et al. 2025
The Results section reports substantial loss of DNA-repair genes in the W/S clade alongside accelerated evolutionary rates, and its mutational-pattern analysis suggests deficient DNA repair. It does not establish that the *rate of gene loss* was accelerated; the acceleration it documents is in evolutionary rates. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn 12 genomes, four or more Cit homologs were found, and the only genome where no citrate synthase gene could be identified belongs to Hanseniaspora jakobsenii, a member of a clade known for multiple gene losses and high divergence.
“In 12 genomes, we found four or more Cit homologs, and the only genome where no citrate synthase gene could be identified belongs to Hanseniaspora jakobsenii—a member of a clade known for multiple gene losses and high divergence (Steenwyk et al. 2019; Gonçalves et al. 2025).”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Gonçalves et al. 2025
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Łabędzka-Dmoch, K., Bui, T. H. D., Piątkowski, J., Dilling, M., Jagiełło, P., Kabza, W., & Golik, P. (2026) · Molecular Biology and Evolution · doi:10.1093/molbev/msag005 · Cited by 1 · see citing works
- Authors
- Gonçalves, C., Steenwyk, J. L., Rinker, D. C., Opulente, D. A., LaBella, A. L., Harrison, M.-C., Wolters, J. F., Zhou, X., Shen, X.-X., Covo, S., Groenewald, M., Hittinger, C. T., & Rokas, A.
- Affiliations
- Vanderbilt University (US)
- Howard Hughes Medical Institute (US)
- University of Wisconsin–Madison (US)
- University of North Carolina at Charlotte (US)
- South China Agricultural University (CN)
- Hebrew University of Jerusalem (IL)
- Westerdijk Fungal Biodiversity Institute (NL)
- Corresponding author
- Rokas, Antonis
- ORCID
- Venue
- Molecular Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2025-10-29
- Volume
- 42
- Issue
- 11
- ISSN
- 0737-4038 (ISSN-L)
- 1537-1719
- PMC
- PMC12629084
- OpenAlex
- W4415841351
- Cited by
- 4
- References
- 112
- Citations by year
- 2026: 4
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Biology and Evolution (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Funders
- National Science Foundation (DEB-2110403, DEB-2110404)
- DOE Great Lakes Bioenergy Research Center
- BER Office of Science (DE-SC0018409)
- USDA National Institute of Food and Agriculture (1020204)
- USDA National Institute of Food and Agriculture Hatch (7005101)
- Office of the Vice Chancellor for Research and Graduate Education
- Wisconsin Alumni Research Foundation
- National Institutes of Health/National Institute of Allergy and Infectious Diseases (R01 AI153356)
- Burroughs Wellcome Fund
- National Key R&D Program of China (2022YFD1401600)
- National Science Foundation for Distinguished Young Scholars of Zhejiang Province (LR23C140001)
- Central Universities (226-2023-00021)
- National Institutes of Health (T32 HG002760-16)
- National Science Foundation Grant Postdoctoral Research Fellowship in Biology (1907278)
- Fundação para a Ciência e a Tecnologia (PTDC/BIA-EVL/0604/2021, UIDP/04378/2020, UIDB/04378/2020, LA/P/0140/2020)
- Howard Hughes Medical Institute Awardee of the Life Sciences Research Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- mutator phenotype, genome stability, DNA repair genes, accelerated evolution, Saccharomycotina, yeast genome, Hanseniaspora, horizontal gene transfer, photolyase, endogenous DNA damage, gene loss, macroevolution
- MeSH terms
- Ascomycota, DNA Repair, Mutation, Phylogeny, Genome, Fungal, Evolution, Molecular, Genomic Instability
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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