Transient genotype-by-environment interactions following environmental shock provide a source of expression variation for essential genes

Abstract

Understanding complex genotype-by-environment interactions (GEIs) is crucial for understanding phenotypic variation. An important factor often overlooked in GEI studies is time. We measured the contribution of GEIs to expression variation in four nonlaboratory Saccharomyces cerevisiae strains responding dynamically to a 25 degrees -37 degrees heat shock. GEI was a major force explaining expression variation, affecting 55% of the genes analyzed. Importantly, almost half of these expression patterns showed GEI influence only during the transition between environments, but not in acclimated cells. This class reveals a genotype-by-environment-by-time interaction that affected expression of a large fraction of yeast genes. Strikingly, although transcripts subject to persistent GEI effects were enriched for nonessential genes with upstream TATA elements, those displaying transient GEIs were enriched for essential genes regardless of TATA regulation. Genes subject to persistent GEI influences showed relaxed constraint on acclimated gene expression compared to the average yeast gene, whereas genes restricted to transient GEIs did not. We propose that transient GEI during the transition between environments provides a previously unappreciated source of expression variation, particularly for essential genes.

Figure 1.—

Expression patterns of representative genes subject to persistent GEI or transient GEI effects. Gene groups were manually selected from hierarchically clustered expression data, clustered over all genes with persistent GEI or with transient GEI effects. The average log₂ expression change across genes in each group is shown for each strain and for the mean of all strains, according to the key in the bottom right. Expression was normalized to the 25° expression levels in each strain for clarity. Average expressions are shown of (A) 30 genes enriched for mitochondrial ribosomal protein genes and displaying persistent GEI, (B) 49 genes enriched for rRNA processing factors and displaying persistent GEI, (C) 34 genes enriched for proteasome subunits and showing transient GEI effects, and (D) 74 genes enriched for ribosomal protein genes and displaying transient GEI influence. In all cases, functional enrichment was significant at a Bonferroni-corrected P < 0.05 (see Table 2). Time points with statistically significant variation (P < 0.01, ANOVA) are indicated with an asterisk; two time points of marginal significance (P = 0.055) are indicated with a +.

Figure 2.—

Contribution of genetic, environmental, and GEI effects to expression variation. The proportion of variance explained by genetic (G), environmental (E), and GEI factors was computed from the ANOVA sums of squares. (A) Box plots show the contribution of G, E, and GEI to expression variation at each time point, for all genes with persistent (left) and transient (right) GEI effects. (B) Triangle plots show the contribution of G, E, and GEI to expression variation of 1744 genes from M22 (scored against the mean of all strains), for genes in the persistent GEI class (top) and the transient GEI class (bottom) at 5, 30, 45, and 120 min after heat shock. Each gene is represented as a single point whose coordinates indicate the proportion of variance explained by each factor.

Figure 3.—

Genes affected by GEI show different levels of purifying selection. The log₂ difference in the median V_g/V_m was measured for each indicated group vs. all remaining genes analyzed. Negative values indicate smaller ratios and positive values represent larger ratios than the comparison group. TATA-less persistent-GEI genes were scored against all remaining TATA-less genes. Statistically significant differences (P < 0.05, Wilcoxon's rank-sum test) are indicated with an asterisk. See text for P-values.