Gene expression is stable despite widespread cis and trans regulatory divergence in Saccharomyces yeasts
Abstract
Regulatory evolution can alter phenotypes, but cis- and trans-regulatory mechanisms may also diverge extensively while total transcript abundance remains stable. Comparisons of parental expression with allele-specific expression in F1 hybrids provide a framework for separating cis- and trans-regulatory effects because both parental alleles are measured in a shared trans-regulatory environment. Here, we analyzed RNA sequencing data from Saccharomyces cerevisiae, S. paradoxus, and their F1 hybrid. Among the 4,164 genes with sufficient allele-specific support for strict classification, 2,134 (51.2%) showed detectable cis- and/or trans-regulatory divergence. However, hybrid expression remained largely conserved, with 81.5% of genes not significantly different from either parent. Compensatory cis–trans divergence predominated over reinforcing divergence; cross-replicate estimation reduced the apparent magnitude of this excess, but opposite-sign effects remained predominant in all 20 nonoverlapping replicate comparisons. To connect gene expression to genome sequence, we analyzed the strongly cis-diverged locus LYS2 and found species differences in promoter architecture, including an S. cerevisiae-specific AT-rich insertion, altered spacing among candidate regulatory features, and a promoter-proximal TATA-like element unique to S. cerevisiae. Sequence-based nucleosome prediction suggests that these differences create a broader promoter-proximal nucleosome-depleted region in S. cerevisiae than in S. paradoxus. We also quantified allele-resolved intron retention and found that it was broadly conserved, with only rare locus-specific hybrid-associated shifts. Together, these results show that regulatory divergence is widespread but often buffered in the hybrid, whereas intron-retention divergence is comparatively limited.
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BibTeX
@article{rojas2026gene,
title = {{Gene expression is stable despite widespread cis and trans regulatory divergence in Saccharomyces yeasts}},
author = {Danithza S Rojas and Gregory I Lang},
journal = {Genetics},
year = {2026},
month = aug,
doi = {10.1093/genetics/iyag233},
url = {https://doi.org/10.1093/genetics/iyag233},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Gene expression is stable despite widespread cis and trans regulatory divergence in Saccharomyces yeasts
AU - Danithza S Rojas
AU - Gregory I Lang
PY - 2026
DA - 2026/08/31
JO - Genetics
DO - 10.1093/genetics/iyag233
UR - https://doi.org/10.1093/genetics/iyag233
AB - Regulatory evolution can alter phenotypes, but cis- and trans-regulatory mechanisms may also diverge extensively while total transcript abundance remains stable. Comparisons of parental expression with allele-specific expression in F1 hybrids provide a framework for separating cis- and trans-regulatory effects because both parental alleles are measured in a shared trans-regulatory environment. Here, we analyzed RNA sequencing data from Saccharomyces cerevisiae, S. paradoxus, and their F1 hybrid. Among the 4,164 genes with sufficient allele-specific support for strict classification, 2,134 (51.2%) showed detectable cis- and/or trans-regulatory divergence. However, hybrid expression remained largely conserved, with 81.5% of genes not significantly different from either parent. Compensatory cis–trans divergence predominated over reinforcing divergence; cross-replicate estimation reduced the apparent magnitude of this excess, but opposite-sign effects remained predominant in all 20 nonoverlapping replicate comparisons. To connect gene expression to genome sequence, we analyzed the strongly cis-diverged locus LYS2 and found species differences in promoter architecture, including an S. cerevisiae-specific AT-rich insertion, altered spacing among candidate regulatory features, and a promoter-proximal TATA-like element unique to S. cerevisiae. Sequence-based nucleosome prediction suggests that these differences create a broader promoter-proximal nucleosome-depleted region in S. cerevisiae than in S. paradoxus. We also quantified allele-resolved intron retention and found that it was broadly conserved, with only rare locus-specific hybrid-associated shifts. Together, these results show that regulatory divergence is widespread but often buffered in the hybrid, whereas intron-retention divergence is comparatively limited.
SN - 0016-6731
SN - 1943-2631
ER -