Abstract
Viruses are known to have some of the highest and most diverse mutation rates found in any biological replicator, with single-stranded (ss) RNA viruses evolving the fastest, and double-stranded (ds) DNA viruses having 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 still unclear. To understand how these two processes affect the long-term evolution of viruses infecting humans, we comprehensively analyzed ssRNA, ssDNA, dsRNA, and dsDNA viruses, to find which virus types and which functions show evidence for episodic diversifying selection and correlated evolution. We show that selection mostly affects single stranded viruses, that correlated evolution is more prevalent in DNA viruses, and that both processes, taken independently, mostly affect viral replication. However, the genes that are jointly 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 it is the joint action of selection and correlated evolution, and not just selection, that shapes the evolutionary trajectories of viruses—and possibly of their epidemiological potential.
Highlights
Humanity is regularly reminded of the epidemiological toll of viruses, in part due to recent and ongoing viral outbreaks of influenza [1], Ebola [2], and Zika [3]
Typical examples include drug resistance mutations that have a fitness cost, and that require a second mutation to compensate for the first one [10], or tRNAs that require a specific base-pairing to maintain their secondary and tertiary structures, so that a mutation in the stem region necessitates a second mutation to restore the correct, functional, structure [11]. This process is of particular interest as correlated evolution can be underlain by epistasis, which occurs when the fitness effects of these two mutations are non-additive [12], as in the two examples above
In order to better understand the genomic characteristics of the four types of viruses known to infect humans, dsDNA (n = 94), dsRNA (n = 15), ssRNA (n = 354), and ssDNA (n = 84), and understand how these characteristics can impact the evolutionary dynamics of these viruses (Methods; Figure S1), we examined the distribution of four of their genomic features
Summary
Humanity is regularly reminded of the epidemiological toll of viruses, in part due to recent and ongoing viral outbreaks of influenza [1], Ebola [2], and Zika [3]. The processes driving the evolution of different types of viruses are multiple As already argued, both ssDNA and ssRNA viruses share small genome sizes, high mutation rates, and large effective population sizes, little to no gene duplication or recombination, and overlapping reading frames [6]. Both ssDNA and ssRNA viruses share small genome sizes, high mutation rates, and large effective population sizes, little to no gene duplication or recombination, and overlapping reading frames [6] This last point suggests that a less frequently explored evolutionary process in viral studies, correlated evolution, could be as critical
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