Gene Essentiality Is a Quantitative Property Linked to Cellular Evolvability

Cell. 2015 Dec 3;163(6):1388-99. doi: 10.1016/j.cell.2015.10.069. Epub 2015 Nov 25.


Gene essentiality is typically determined by assessing the viability of the corresponding mutant cells, but this definition fails to account for the ability of cells to adaptively evolve to genetic perturbations. Here, we performed a stringent screen to assess the degree to which Saccharomyces cerevisiae cells can survive the deletion of ~1,000 individual "essential" genes and found that ~9% of these genetic perturbations could in fact be overcome by adaptive evolution. Our analyses uncovered a genome-wide gradient of gene essentiality, with certain essential cellular functions being more "evolvable" than others. Ploidy changes were prevalent among the evolved mutant strains, and aneuploidy of a specific chromosome was adaptive for a class of evolvable nucleoporin mutants. These data justify a quantitative redefinition of gene essentiality that incorporates both viability and evolvability of the corresponding mutant cells and will enable selection of therapeutic targets associated with lower risk of emergence of drug resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Evolution*
  • Gene Deletion
  • Genes, Essential*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Saccharomyces cerevisiae / classification
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Spores, Fungal / metabolism


  • Brr6 protein, S cerevisiae
  • Membrane Proteins
  • NUP57 protein, S cerevisiae
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins

Associated data

  • SRA/SRP045259