Exploring whole-genome duplicate gene retention with complex genetic interaction analysis

Science. 2020 Jun 26;368(6498):eaaz5667. doi: 10.1126/science.aaz5667.


Whole-genome duplication has played a central role in the genome evolution of many organisms, including the human genome. Most duplicated genes are eliminated, and factors that influence the retention of persisting duplicates remain poorly understood. We describe a systematic complex genetic interaction analysis with yeast paralogs derived from the whole-genome duplication event. Mapping of digenic interactions for a deletion mutant of each paralog, and of trigenic interactions for the double mutant, provides insight into their roles and a quantitative measure of their functional redundancy. Trigenic interaction analysis distinguishes two classes of paralogs: a more functionally divergent subset and another that retained more functional overlap. Gene feature analysis and modeling suggest that evolutionary trajectories of duplicated genes are dictated by combined functional and structural entanglement factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Deletion
  • Gene Duplication*
  • Gene Regulatory Networks
  • Genes, Duplicate*
  • Genetic Techniques
  • Genome, Fungal*
  • Membrane Proteins / genetics
  • Peroxins / genetics
  • Protein Interaction Maps / genetics*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics*


  • Membrane Proteins
  • PEX25 protein, S cerevisiae
  • Peroxins
  • Pex27 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins

Associated data

  • Dryad/10.5061/dryad.g79cnp5m9