Direct selection on genetic robustness revealed in the yeast transcriptome

Abstract

Background: Evolutionary theory predicts that organisms should evolve the ability to produce high fitness phenotypes in the face of environmental disturbances (environmental robustness) or genetic mutations (genetic robustness). While several studies have uncovered mechanisms that lead to both environmental and genetic robustness, we have yet to understand why some components of the genome are more robust than others. According to evolutionary theory, environmental and genetic robustness will have different responses to selective forces. Selection on environmental robustness for a trait is expected to be strong and related to the fitness costs of altering that trait. In contrast to environmental robustness, selection on genetic robustness for a trait is expected to be largely independent of the fitness cost of altering the trait and instead should correlate with the standing genetic variation for the trait that can potentially be buffered. Several mechanisms that provide both environmental and genetic robustness have been described, and this correlation could be explained by direct selection on both forms of robustness (direct selection hypothesis), or through selection on environmental robustness and a correlated response in genetic robustness (congruence hypothesis).

Methodology/principal findings: Using both published and novel data on gene expression in the yeast Saccharomyces cerevisiae, we find that genetic robustness is correlated with environmental robustness across the yeast genome as predicted by the congruence hypothesis. However, we also show that environmental robustness, but not genetic robustness, is related to per-gene fitness effects. In contrast, genetic robustness is significantly correlated with network position, suggesting that genetic robustness has been under direct selection.

Conclusions/significance: We observed a significant correlation between our measures of genetic and environmental robustness, in agreement with the congruence hypothesis. However, this correlation alone cannot explain the co-variance of genetic robustness with position in the protein interaction network. We therefore conclude that direct selection on robustness has played a role in the evolution of genetic robustness in the transcriptome.

Figure 1. A schematic diagram illustrating the role that network position can play in propagation of noise through the network.

The circles in the diagram represent genes while the lines represent bi-directional interactions (like protein-protein interactions). The diagram shows how a focal node, shown in red, can affect noise produced by a perturbed node, shown in blue. The noise produced by the blue gene is represented by the blue oscillating arrows, and is dampened after passing through the red gene. Because the red gene lies on pathways between many other genes it has a large potential to buffer genetic noise.

Figure 2. The relationship between environmental expression robustness and two forms of genetic robustness.

The data were separated into 15 bins based on ranked environmental robustness. For each bin the mean and standard error of each form of robustness was calculated. Filled squares indicate robustness to knockouts while open squares indicate robustness to background genotype. All statistical analyses were carried out on the un-binned data.

Figure 3. Correlation between residual GR and residual BR.

We independently fit GR and BR to ER and performed a linear regression. Residual values of GR and BR were calculated and are shown here. The measures are significantly correlated with Spearman's ρ of 0.15 and a Pearson's r of 0.16.