Robustness against mutations in genetic networks of yeast

Nat Genet. 2000 Apr;24(4):355-61. doi: 10.1038/74174.


There are two principal mechanisms that are responsible for the ability of an organism's physiological and developmental processes to compensate for mutations. In the first, genes have overlapping functions, and loss-of-function mutations in one gene will have little phenotypic effect if there are one or more additional genes with similar functions. The second mechanism has its origin in interactions between genes with unrelated functions, and has been documented in metabolic and regulatory gene networks. Here I analyse, on a genome-wide scale, which of these mechanisms of robustness against mutations is more prevalent. I used functional genomics data from the yeast Saccharomyces cerevisiae to test 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. My results demonstrate that interactions among unrelated genes are the major cause of robustness against mutations. This type of robustness is probably an evolved response of genetic networks to stabilizing selection.

MeSH terms

  • Computational Biology
  • Evolution, Molecular
  • Gene Duplication
  • Gene Expression Regulation, Fungal
  • Genes, Regulator
  • Models, Genetic
  • Mutation*
  • Phenotype
  • Saccharomyces cerevisiae / genetics*
  • Selection, Genetic