Minimization of biosynthetic costs in adaptive gene expression responses of yeast to environmental changes

Abstract

Yeast successfully adapts to an environmental stress by altering physiology and fine-tuning metabolism. This fine-tuning is achieved through regulation of both gene expression and protein activity, and it is shaped by various physiological requirements. Such requirements impose a sustained evolutionary pressure that ultimately selects a specific gene expression profile, generating a suitable adaptive response to each environmental change. Although some of the requirements are stress specific, it is likely that others are common to various situations. We hypothesize that an evolutionary pressure for minimizing biosynthetic costs might have left signatures in the physicochemical properties of proteins whose gene expression is fine-tuned during adaptive responses. To test this hypothesis we analyze existing yeast transcriptomic data for such responses and investigate how several properties of proteins correlate to changes in gene expression. Our results reveal signatures that are consistent with a selective pressure for economy in protein synthesis during adaptive response of yeast to various types of stress. These signatures differentiate two groups of adaptive responses with respect to how cells manage expenditure in protein biosynthesis. In one group, significant trends towards downregulation of large proteins and upregulation of small ones are observed. In the other group we find no such trends. These results are consistent with resource limitation being important in the evolution of the first group of stress responses.

Figure 1. Spearman rank correlation between properties of proteins and changes in gene expression for each stress condition.

Only the results with statistical significance (p<0.05) are shown. Green bars correspond to upregulation. Purple bars correspond to downregulation.

Figure 2. Change-folds of genes with respect to their length.

Plots show the moving-median using a window of 300 elements. Colors: Green for upregulation and purple for downregulation. Length unit is 10² amino acids. The lines represent the moving median plots. The shaded areas represent the regions from quantile 0.25 to quantile 0.75. Note that in most cases there is an upper limit to the length of upregulated proteins. This limit is smaller than the limit found for to the length of downregulated proteins.

Figure 3. Cluster analysis of the different stress responses.

Basal Cluster corresponds to adaptive responses that may occur under energy or resources shortage. Trends in up- and downregulation of genes after stress. (A) Upregulation trend with respect abundance, (B) Downregulation trend with respect abundance, (C) Upregulation trend with respect length, (D) Downregulation trend with respect length. In each case, a (+) result indicates a significant result in the expected direction, (−) means a significant result opposite to the expected one, (o) indicates a non-significant result in the Mann-Whitney analysis. All correlations shown here have p<0.05 and p≤0.06 if *.

Figure 4. Comparison of the distribution of biosynthetic cost estimates among cellular component GO categories for the various stresses.

The values are normalized so that the maximum calculated value of the index in the whole dataset is 1 and the minimum is 0. The basal condition is rescaled to 0.97 and would plot as a circle.

Figure 5. Change-folds of genes in the lumped stress responses with respect to their length and abundance.

The plot is the result of moving-quantile 0.75, 0.5 and 0.25 with a window of 300 elements. Green for up-expressed genes and purple for down-expressed. Length is divided by 10² amino acids.

Figure 6. Change-folds of gene expression with respect to their length, binned by their basal abundance.

Moving-median plots were calculated using a window of 300 elements. Green - upregulated genes; Purple - downregulated genes. (A) Plot by bins of abundance: (A.1) for proteins with abundance <876 protein per cell, (A.2) abundance between 876 and 2253, (A.3) abundance between 2253 and 6232, and (A.4) if abundance is ≥6232, (B) Shows the results for all bins separated by upregulation (B.1) and downregulation (B.2). Length unit is 10² amino acids and Abundance unit is 10³ pr/cell.

Figure 7. Comparison of the change-fold between proteins that are part of a complex and those that are not.

Quantile-quantile plots show the divergence between the two lists by the deviation of the points from the line with a slope of 1. (A) Tendencies of the up-expression change-folds; (B) Tendencies of the down-expression change-folds.