Roles of Trans and Cis Variation in Yeast Intraspecies Evolution of Gene Expression

Abstract

Both cis and trans mutations contribute to gene expression divergence within and between species. We used Saccharomyces cerevisiae as a model organism to estimate the relative contributions of cis and trans variations to the expression divergence between a laboratory (BY) and a wild (RM) strain of yeast. We examined whether genes regulated by a single transcription factor (TF; single input module, SIM genes) or genes regulated by multiple TFs (multiple input module, MIM genes) are more susceptible to trans variation. Because a SIM gene is regulated by a single immediate upstream TF, the chance for a change to occur in its trans-acting factors would, on average, be smaller than that for a MIM gene. We chose 232 genes that exhibited expression divergence between BY and RM to test this hypothesis. We examined the expression patterns of these genes in a BY-RM coculture system and in a BY-RM diploid hybrid. We found that trans variation is far more important than cis variation for expression divergence between the two strains. However, because in 75% of the genes studied, cis variation has significantly contributed to expression divergence, cis change also plays a significant role in intraspecific expression evolution. Interestingly, we found that the proportion of genes with diverged expression between BY and RM is larger for MIM genes than for SIM genes; in fact, the proportion tends to increase with the number of transcription factors that regulate the gene. Moreover, MIM genes are, on average, subject to stronger trans effects than SIM genes, though the difference between the two types of genes is not conspicuous.

The genetic basis of evolutionary change in gene expression levels

“…The methodological requirement for measuring ASE can be met through pyrosequencing for moderate numbers of genes (Wittkopp et al 2004Sung et al 2009 In ASE experiments, variation is detected in a comparison of expression levels between two alleles in homozygous or hemizygous parental strains (figure 3, top row). Then the difference in expression between alleles is assayed again in the heterozygote (F 1 ).…”

“…In attempting to investigate why heterosis is so common in maize, answers have been sought through examining the dominance of variation found through ASE studies, although current work is inconclusive and can only provide speculations on the precise relationship between the dominance of ASE patterns and hybrid vigour (Springer & Stupar 2007b;Stupar et al 2007Stupar et al , 2008. The intraspecific studies in yeast and Arabidopsis differ from the maize studies in that they either find a substantially larger number of genes shown to be acting in trans fashion than in cis (Sung et al 2009;Emerson et al 2010) or similar numbers of both, with a slightly larger number of trans interactions (Zhang & Borevitz 2009). The study in D. simulans showed that cis ASE variation predominated over trans variation, though this was observed only in a sample of five genes (Main et al 2009).…”

Natural selection on cis and trans regulation in yeasts

“…These experiments in Drosophila on 78 genes showed that cis differences dominate between species more than within species (Wittkopp et al 2008). ASE polymorphism studies in yeast have found that expression level variation is usually numerically dominated by trans variants (Wang et al 2007;Sung et al 2009), even when single-input module genes were chosen to minimize the impact of trans variation (Wang et al 2007). Additionally, in yeast only 52%-78% of expression QTLs mapped to the same region as the gene they regulate were confirmed to be cis (Ronald et al 2005), implying that as much as 22%-48% of genes with local linkages might be regulated in trans.…”

Analysis ofCryptococcus neoformansSexual Development Reveals Rewiring of the Pheromone-Response Network by a Change in Transcription Factor Identity

“…The lack of bioinformatic predictive power to resolve this question poses a unique opportunity to gain insight into the evolution of the pheromone-response network, because a nonconserved regulator must carry out this conserved function. In other systems, studies have shown that regulatory network evolution is directed by changes in (1) transcription-factor identity and/or behavior, (2) transcription-factor binding sites in DNA, and (3) cohorts of regulated genes (Davidson EH et al 2002;Gasch et al 2004;Borneman et al 2007;Sung et al 2009;Booth et al 2010;Wilczynski and Furlong 2010;Baker et al 2011). A recent discovery by Lin et al (2010) implicated the more divergent HMG-domain regulator (Mat2) in pheromone signaling.…”