Episodic diversifying selection and intragenomic interactions shape the evolution of DNA and RNA viruses

Viruses are known to have some of the highest and most diverse mutation rates found in any biological replicator, topped by single-stranded (ss) RNA viruses, while double-stranded (ds) DNA viruses have rates approaching those of bacteria. As mutation rates are tightly and negatively correlated with genome size, selection is a clear driver of viral evolution. However, the role of intragenomic interactions as drivers of viral evolution is less well documented. To understand how these two processes affect viral evolution, we systematically surveyed ssRNA, ssDNA, dsRNA, and dsDNA viruses, to find which virus type and which functions show evidence for episodic diversifying selection and correlated evolution. We show that while evidence for selection is mostly found in single stranded viruses, and correlated evolution is more prevalent in DNA viruses, the genes that are affected by both processes are involved in key aspects of their life cycle, favoring viral stability over proliferation. We further show that both evolutionary processes are intimately linked at the amino acid level, which suggests that selection alone does not explain the whole evolutionary —and epidemiological— potential of viruses.