Transcriptomic and proteomic effects of gene deletion are not evolutionarily conserved

Abstract

Although the textbook definition of gene function is the effect for which the gene was selected and/or by which it is maintained, gene function is commonly inferred from the phenotypic effects of deleting the gene. Because some of the deletion effects are byproducts of other effects, they may not reflect the gene’s selected-effect function. To evaluate the degree to which the phenotypic effects of gene deletion inform gene function, we compare the transcriptomic and proteomic effects of systematic gene deletions in budding yeast (Saccharomyces cerevisiae) with those effects in fission yeast (Schizosaccharomyces pombe). Despite evidence for functional conservation of orthologous genes, their deletions result in no more sharing of transcriptomic or proteomic effects than that from deleting nonorthologous genes. Because the wild-type mRNA and protein levels of orthologous genes are significantly correlated between the two yeasts and because transcriptomic effects of deleting the same gene strongly overlap between studies in the same S. cerevisiae strain by different laboratories, our observation cannot be explained by rapid evolution or large measurement error of gene expression. Analysis of transcriptomic and proteomic effects of gene deletions in multiple S. cerevisiae strains by the same laboratory reveals a high sensitivity of these effects to the genetic background, explaining why these effects are not evolutionarily conserved. Together, our results suggest that most transcriptomic and proteomic effects of gene deletion do not inform selected-effect function. This finding has important implications for assessing and/or understanding gene function, pleiotropy, and biological complexity.