The Role of Cis-Regulatory Motifs and Genetical Control of Expression in the Divergence of Yeast Duplicate Genes

Expression divergence of duplicate genes is widely believed to be important for their retention and evolution of new function, although the mechanism that determines their expression divergence remains unclear. We use a genetical genomics approach to explore divergence in genetical control of yeast duplicate genes created by a whole-genome duplication that occurred about 100 MYA and those with a younger duplication age. The analysis reveals that duplicate genes have a significantly higher probability of sharing common genetic control than pairs of singleton genes. The expression quantitative trait loci (eQTLs) have diverged completely for a high proportion of duplicate pairs, whereas a substantially larger proportion of duplicates share common regulatory motifs after 100 Myr of divergent evolution. The similarity in both genetical control and cis motif structure for a duplicate pair is a reflection of its evolutionary age. This study reveals that up to 20% of variation in expression between ancient duplicate gene pairs in the yeast genome can be explained by both cis motif divergence (approximately 8%) and by trans eQTL divergence (approximately 10%). Initially, divergence in all 3 aspects of cis motif structure, trans-genetical control, and expression evolves coordinately with the coding sequence divergence of both young and old duplicate pairs. These findings highlight the importance of divergence in both cis motif structure and trans-genetical control in the diverse set of mechanisms underlying the expression divergence of yeast duplicate genes.