Expression evolution in yeast genes of single-input modules is mainly due to changes in trans-acting factors

Abstract

Both cis-and trans-regulatory mutations contribute to gene expression divergence within and between species. To estimate their relative contributions, we examined two yeast strains, BY (a laboratory strain) and RM (a wild strain), for their gene-expression divergence by microarray. Using these data and published ChIP-chip data, we obtained a set of single-regulator-regulated genes that showed expression divergence between BY and RM. We randomly selected 50 of these genes for further study. We developed a step-by-step approach to assess the relative contributions of cisand trans-variations to expression divergence by using pyrosequencing to quantify the mRNA levels of the BY and RM alleles in the same culture (co-culture) and in hybrid diploids. Forty genes showed expression divergence between the two strains in co-culture, and pyrosequencing of the BY/RM hybrid diploids showed that 45% (18/40) can be attributed to differences in trans-acting factors alone, 17.5% (7/40) mainly to trans-variations, 20% (8/40) to both cis-and trans-acting factors, 7.5% (3/40) mainly to cis-variations, and 10% (4/40) to cis-acting factors alone. In addition, we replaced the BY promoter by the RM promoter in each of 10 BY genes that were found from our microarray data to have expression divergence between BY and RM, and in each case our quantitative PCR analysis revealed a cis effect of the promoter replacement on gene expression. In summary, our study suggests that trans-acting factors play the major role in expression evolution between yeast strains, but the role of cis variation is also important.

Gene balance hypothesis: Connecting issues of dosage sensitivity across biological disciplines

“…These studies suggest that the apparent regulatory variation, as opposed to individual target gene expression, is more constrained. In other studies of cis and trans variation, cis variation for a target gene varies to greater magnitude than trans regulatory variation, which is, however, multigenic if the variation is great enough to be detected (122)(123)(124)(125)(126)(127)(128)(129)(130)(131)(132)(133)(134). The multigenic lowmagnitude transacting effects on gene expression, the mutation accumulation results, and the finding that members of protein complexes that exhibit dosage effects have limited variation form a consistent set of observations suggesting that there is a generalized constraint on regulatory variation.…”

Complex genetic interactions underlying expression differences between Drosophila races: Analysis of chromosome substitutions

“…By integrating transcriptional profiling and linkage analysis, Hubner et al (7) have shown that 35-40% of the eQTLs between two mouse strains were regulated in cis. In yeast the proportion of cis eQTL from different studies ranges from 10% to 25% (1,9,25). The differences may, to some degree, depend on the level of divergence analyzed.…”

“…(cis regulation refers to the control of expression by the gene itself whereas trans regulation refers to the influence of the genetic background.) Many studies have addressed this question at various levels of divergence (1)(2)(3)(4)(5)(6)(7)(8)(9). For example, one may measure the expressions of two alleles at the locus of interest in a common genetic background (usually F 1 s) (1,2,5).…”

Evidence of Spatially Varying Selection Acting on Four Chromatin-Remodeling Loci in Drosophila melanogaster

“…Recent work on the evolution of gene expression has focused largely on local regulatory elements (cis-regulation; Gompel et al 2005;Wittkopp 2006) or on the expression/activity of proteins that interact with such sequences (trans-regulation; Wittkopp et al 2004;Wang et al 2007). These DNA-transcription factor interactions, however, compose only one component of gene regulation.…”