Loss of homomeric interactions and heteromers formation is the long-term fate of duplicated homomers

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. To delineate the evolutionary fates of duplicated oligomers, we analyzed all S. cerevisiae and E. coli oligomeric complexes that include paralogous proteins. We found that although the proportion of homo-hetero duplication fates strongly depended on a variety of factors, rigorous filtering gave a consistent picture. While in E. coli about half of the paralogous pairs are homomeric, in S. cerevisiae, a eukaryote which diverged later, only ~10% of paralogs kept the ancestral homomeric interaction. Accordingly, we show that homomeric bacterial proteins diverged to heteromeric complexes in yeast. Our analysis reconciles contradicting trends and conflicting previous analyses, and provides deeper understanding of how the fate of duplicated genes depends on evolutionary time and protein function.