Uncovering genetic regulatory network divergence between duplicate genes using yeast eQTL landscape

Abstract

Genetical genomics, a novel approach combining microarray technology and quantitative genetic analysis, aims to identify the expression quantitative trait loci (eQTLs), which may regulate the genome-wide expression pattern. In this article, we have studied yeast genomic eQTL data to investigate how the genetic eQTL regulation of ancestral gene has diverged since gene duplication. Our findings are as follows: (i) Duplicate genes have higher heritability for gene expression than single-copy genes, but little difference in their epistasis and directional effect. (ii) The divergence of trans-acting eQTLs between duplicate pairs increases with the evolutionary time since gene duplication. (iii) Trans-acting eQTL divergence can explain about 21% of the variation in expression divergence between duplicate pairs with K(S)<2.0, which increases to 27% when the transcription factor (TF)-target interaction divergence is combined. Moreover, under the partial correlation analysis, trans-acting eQTL divergence seems make a bigger contribution to expression divergence than does TF divergence. (iv) Trans-acting eQTL divergence between duplicate pairs is correlated with gene ontology categories "Biological processes" and "Cellular components," but not with "Molecular functions," and is related to fitness defect under treatment conditions, but not with fitness under normal condition. We conclude that eQTL analysis provides a novel approach to explore the effect of gene duplications on the genetic regulatory network.