Determining the interaction status and evolutionary fate of duplicated homomeric proteins

PLoS Comput Biol. 2020 Aug 27;16(8):e1008145. doi: 10.1371/journal.pcbi.1008145. eCollection 2020 Aug.

Abstract

Oligomeric proteins are central to life. Duplication and divergence of their genes is a key evolutionary driver, also because duplications can yield very different outcomes. Given a homomeric ancestor, duplication can yield two paralogs that form two distinct homomeric complexes, or a heteromeric complex comprising both paralogs. Alternatively, one paralog remains a homomer while the other acquires a new partner. However, so far, conflicting trends have been noted with respect to which fate dominates, primarily because different methods and criteria are being used to assign the interaction status of paralogs. Here, we systematically analyzed all Saccharomyces cerevisiae and Escherichia coli oligomeric complexes that include paralogous proteins. We found that the proportions of homo-hetero duplication fates strongly depend on a variety of factors, yet that nonetheless, rigorous filtering gives a consistent picture. In E. coli about 50%, of the paralogous pairs appear to have retained the ancestral homomeric interaction, whereas in S. cerevisiae only ~10% retained a homomeric state. This difference was also observed when unique complexes were counted instead of paralogous gene pairs. We further show that this difference is accounted for by multiple cases of heteromeric yeast complexes that share common ancestry with homomeric bacterial complexes. Our analysis settles contradicting trends and conflicting previous analyses, and provides a systematic and rigorous pipeline for delineating the fate of duplicated oligomers in any organism for which protein-protein interaction data are available.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Evolution*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Gene Duplication
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Escherichia coli Proteins
  • Saccharomyces cerevisiae Proteins

Grants and funding

This work is supported by the Estate of Mark Scher, and by Israel Science Foundation grant No. 2575/20. S.M. was supported by PBC-VATAT Postdoctoral Fellowship, provided by the Council for Higher Education, Israel. D.S.T. is the Nella and Leon Benoziyo Professor of Biochemistry at WIS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.