Evidences for increased expression variation of duplicate genes in budding yeast: from cis- to trans-regulation effects

Duplicate genes tend to have a more variable expression program than singleton genes, which was thought to be an important way for the organism to respond and adapt to fluctuating environment. However, the underlying molecular mechanisms driving such expression variation remain largely unexplored. In this work, we first rigorously confirmed that duplicate genes indeed have higher gene expression variation than singleton genes in several aspects, i.e. responses to environmental perturbation, between-strain divergence, and expression noise. To investigate the underlying mechanism, we further analyzed a previously published expression dataset of yeast segregants produced from genetic crosses. We dissected the observed expression divergence between segregant strains into cis- and trans-variabilities, and demonstrated that trans-regulation effect can explain larger fraction of the expression variation than cis-regulation effect. This is true for both duplicate genes and singleton genes. In contrast, we found, between a pair of sister paralogs, cis-variability explains more of the expression divergence between the paralogs than trans-variability. We next investigated the presence of cis- and trans-features that are associated with elevated expression variations. For cis-acting regulation, duplicate genes have higher genetic diversity in their promoters and coding regions than singleton genes. For trans-acting regulation, duplicate and singleton genes are differentially regulated by chromatin regulators and transcription factors, and duplicate genes are more severely affected by the deletion of histone tails. These results showed that both cis-and trans-factors have great effect in causing the increased expression variation of duplicate genes, and explained the previously observed differences in transcription regulation between duplicate genes and singleton genes.