Age-specific genomic and transcriptomic variation reveals limited evidence for cis-regulatory interactions modulating aging in Saccharomyces cerevisiae
- 1Department of Integrative Biology, Oregon State University , 2701 SW Campus Way, Corvallis, OR 97331 ,
Abstract
The budding yeast Saccharomyces cerevisiae is a well-established model for studying the genetic basis of complex traits, and it is a powerful system for investigating mechanisms of aging. Here, we examine the genomic and transcriptomic factors contributing to increased replicative age in recombinant yeast populations harboring standing genetic variation. Using fluorescence-activated cell sorting, we isolated young and aged cohort pairs across 12 biological replicates and sequenced their progeny to assess patterns of differentiation at the nucleotide and transcription levels. Most differentiated alleles were located in coding regions, including significant variants within 132 unique genes. Transcriptomic analysis revealed 60 differentially expressed genes in aged populations, including 18 genes with increased expression in aged cohorts, and 42 genes with decreased expression. Although only 2 genes (RFA3 and WSC4) were implicated in both genomic and transcriptomic analyses, functional overlap associated with protein homeostasis, DNA repair, and cell cycle regulation was evident across datasets. Notably, we found no strong evidence that differentially expressed genes were more likely to occur in close proximity to significant gene variants. This suggests that late-life survival is not predominantly governed by background-independent local cis-regulatory interactions. These findings are consistent with a polygenic architecture in which distinct genotypes may promote longevity through diverse regulatory mechanisms.
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BibTeX
@article{mchugh2026agespecific,
title = {{Age-specific genomic and transcriptomic variation reveals limited evidence for cis-regulatory interactions modulating aging in Saccharomyces cerevisiae}},
author = {Kaitlin M McHugh and Felipe S Barreto and Molly K Burke},
journal = {G3: Genes, Genomes, Genetics},
year = {2026},
month = oct,
doi = {10.1093/g3journal/jkag276},
url = {https://academic.oup.com/g3journal/advance-article/doi/10.1093/g3journal/jkag276/8860174},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Age-specific genomic and transcriptomic variation reveals limited evidence for cis-regulatory interactions modulating aging in Saccharomyces cerevisiae
AU - Kaitlin M McHugh
AU - Felipe S Barreto
AU - Molly K Burke
PY - 2026
DA - 2026/10/03
JO - G3: Genes, Genomes, Genetics
DO - 10.1093/g3journal/jkag276
UR - https://academic.oup.com/g3journal/advance-article/doi/10.1093/g3journal/jkag276/8860174
AB - The budding yeast Saccharomyces cerevisiae is a well-established model for studying the genetic basis of complex traits, and it is a powerful system for investigating mechanisms of aging. Here, we examine the genomic and transcriptomic factors contributing to increased replicative age in recombinant yeast populations harboring standing genetic variation. Using fluorescence-activated cell sorting, we isolated young and aged cohort pairs across 12 biological replicates and sequenced their progeny to assess patterns of differentiation at the nucleotide and transcription levels. Most differentiated alleles were located in coding regions, including significant variants within 132 unique genes. Transcriptomic analysis revealed 60 differentially expressed genes in aged populations, including 18 genes with increased expression in aged cohorts, and 42 genes with decreased expression. Although only 2 genes (RFA3 and WSC4) were implicated in both genomic and transcriptomic analyses, functional overlap associated with protein homeostasis, DNA repair, and cell cycle regulation was evident across datasets. Notably, we found no strong evidence that differentially expressed genes were more likely to occur in close proximity to significant gene variants. This suggests that late-life survival is not predominantly governed by background-independent local cis-regulatory interactions. These findings are consistent with a polygenic architecture in which distinct genotypes may promote longevity through diverse regulatory mechanisms.
SN - 2160-1836
ER -