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

Abstract

Gene expression variation, an essential step between genomic variation and phenotypic landscape, is collectively controlled by local (cis) and distant (trans) regulatory changes. Nevertheless, how these regulatory elements differentially influence the heritability of expression traits remains unclear. Here, we bridge this gap by analyzing the transcriptomes of a large diallel panel consisting of 323 unique hybrids originated from genetically divergent yeast isolates. We estimated the broad- and narrow-sense heritability across 5,087 transcript abundance traits and showed that non-additive components account for 36% of the phenotypic variance on average. By comparing allelic expression ratios in the hybrid and the corresponding parental pair, we identified regulatory changes in 25% of all cases, with a majority acting in trans. We further showed that trans-regulation could underlie coordinated expression variation across highly connected genes, resulting in significantly higher non-additive variance and most likely in some of the missing heritability of gene expression traits. HighlightsO_LIDiallel panel for dissecting genetic components underlying gene expression variation C_LIO_LINon-additive components account for 36% of gene expression trait heritability C_LIO_LIMost cis- regulatory variation is buffered by additional trans-acting variants C_LIO_LIGenes under trans- regulation show high non-additive variance and functional coherence C_LI