The Polyphyletic Origins of Primase-Helicase Bifunctional Proteins

We studied the evolutionary relationships of different primase-helicase bifunctional proteins, found mostly in viruses, virophages, plasmids, and organellar genomes, by phylogeny and correlation analysis. Our study suggests independent origins of primase-helicase bifunctional proteins resulting from multiple fusion events between genes encoding primase and helicase domains of different families. The correlation analysis further indicated strong functional dependencies of domains in the bifunctional proteins that are part of smaller genomes and plasmids. Bifunctional proteins found in some bacterial genomes exhibited weak coevolution probably suggesting that these are the non-functional remnants of the proteins acquired via horizontal transfer. We have put forward possible scenarios for the origin of primase-helicase bifunctional proteins in large eukaryotic DNA viruses and virophages.