The role of structural pleiotropy and regulatory evolution in the retention of heteromers of paralogs

Elife. 2019 Aug 27:8:e46754. doi: 10.7554/eLife.46754.

Abstract

Gene duplication is a driver of the evolution of new functions. The duplication of genes encoding homomeric proteins leads to the formation of homomers and heteromers of paralogs, creating new complexes after a single duplication event. The loss of these heteromers may be required for the two paralogs to evolve independent functions. Using yeast as a model, we find that heteromerization is frequent among duplicated homomers and correlates with functional similarity between paralogs. Using in silico evolution, we show that for homomers and heteromers sharing binding interfaces, mutations in one paralog can have structural pleiotropic effects on both interactions, resulting in highly correlated responses of the complexes to selection. Therefore, heteromerization could be preserved indirectly due to selection for the maintenance of homomers, thus slowing down functional divergence between paralogs. We suggest that paralogs can overcome the obstacle of structural pleiotropy by regulatory evolution at the transcriptional and post-translational levels.

Keywords: S. cerevisiae; epistasis; evolutionary biology; gene duplication; genetics; genomics; pleiotropy; protein interaction networks; regulatory evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology
  • Evolution, Molecular*
  • Gene Duplication*
  • Models, Genetic
  • Mutation, Missense*
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics*

Substances

  • Saccharomyces cerevisiae Proteins

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.