On the Source of Mutational Robustness in Genetic Networks of Yeast

Resilience of an organism's physiological and developmental processes against mutations can have two principal causes, the first being overlapping gene functions. In this case, loss-of-function mutations in one gene will have little phenotypic effects if one or more other genes with similar functions serve as a "back-up". The second cause stems from interactions among genes with unrelated functions, and has been documented in metabolic and regulatory gene networks. The subject of this paper is to analyze, on a genome-wide scale, which of these causes of robustness is more important. To this end, I use functional genomics data from the yeast Saccharomyces cerevisiae to test a series of hypotheses related to the following: If gene duplications are mostly responsible for robustness, then a correlation is expected between the similarity of two duplicated genes and the effect of mutations in one of these genes. The results demonstrate that interactions among unrelated genes are the major cause of robustness against mutations. This type of robustness is unlikely to be an intrinsic property, but is probably an evolved response of genetic networks to stabilizing selection.