Non-additive genetic components contribute significantly to population-wide gene expression variation

Gene expression variation, an essential step between genotype and phenotype, is collectively controlled by local (cis) and distant (trans) regulatory changes. Nevertheless, how these regulatory elements differentially influence gene expression variation remains unclear. Here, we bridge this gap by analyzing the transcriptomes of a large diallel panel consisting of 323 unique hybrids originating from genetically divergent Saccharomyces cerevisiae isolates. Our analysis across 5,087 transcript abundance traits showed that non-additive components account for 36% of the gene expression variance on average. By comparing allele-specific read counts in parent-hybrid trios, we found that trans-regulatory changes underlie the majority of gene expression variation in the population. Remarkably, most cis-regulatory variations are also exaggerated or attenuated by additional trans effects. Overall, we showed that the transcriptome is globally buffered at the genetic level mainly due to trans-regulatory variation in the population. [Display omitted] •Diallel panel for dissecting genetic components underlying gene expression variation•Non-additive components account for 36% of gene expression trait heritability•Most cis-regulatory variation is buffered by additional trans-acting variants•Genes under trans-regulation show high non-additive variance and functional coherence Tsouris et al. generated a large diallel hybrid panel using diverse natural yeast isolates and explored the gene expression variation across this population. They showed that the transcriptome is globally buffered at the genetic level, mainly due to genomic variants that act distantly (i.e., in trans) to the expression traits.