Cited by 4Fungal and yeast genetics researchEvolution and Genetic DynamicsDNA Repair Mechanisms

Stable hypermutators revealed by the genomic landscape of genes involved in genome stability among yeast species

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Gonçalves, Carla, Steenwyk, Jacob L, Rinker, David C, Opulente, Dana A, LaBella, Abigail L, Harrison, Marie-Claire, Wolters, John F, Zhou, Xiaofan +5 more·2025·Molecular Biology and Evolution

Abstract

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 measured
  • In 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).”

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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
Venue
Molecular Biology and Evolution
Published
2025-10-29
Volume
42
Issue
11
ISSN
  • 0737-4038 (ISSN-L)
  • 1537-1719
OpenAlex
W4415841351
Cited by
4
References
112
Citations by year
2026: 4
FWCI
1.20
Type
journal article
Language
en
Open access
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

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