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.

FIG. 1.—

Guidelines for inferring the cis or trans variation effect. (1) Cis effect alone; (2) Trans effect alone; (3) if |R₂ − 1|/|R₁ − 1| ≤ 0.25, between 0.25 and 0.75, or >0.75 (but |R₂ − 1| / |R₁ − 1| ≠ 1), the expression divergence is classified as a major trans effect, “both cis and trans effects” and a major cis effect, respectively; (4) if R₁ > (1/R₂), it is a major trans effect, but if R₁ ≤ (1/R₂), it is due to both cis and trans effects; (5) both cis and trans effects. Here, we define R₁ = RM_cocult/BY_cocult and R₂ = RM_hybrid/BY_hybrid. If R₁ < 1, then define R₁ = BY_cocult/RM_cocult and R₂ = BY_hybrid/RM_hybrid. The SE bar is also shown with the mean (circle).

FIG. 2.—

Relative contributions of trans and cis effects to expression divergence between BY and RM when all 223 genes studied are considered together. Sampling variances were estimated by bootstrapping 500 replicates.

FIG. 3.—

Relative contributions of trans and cis effects to expression divergence between BY and RM for SIM genes, MIM genes, and genes with unknown TFs.

FIG. 4.—

Effects of the number of TFs that regulate a gene on the relative contributions of trans and cis variation to expression divergence.

FIG. 5.—

Effects of expression divergence of TFs on the evolutionary effect of the downstream genes. Sampling variances were estimated by bootstrapping 500 replicates.