Molecular Evolution of Viral Multifunctional Proteins: The Case of Potyvirus HC-Pro

Abstract

Our knowledge on the mode of evolution of the multifunctional viral proteins remains incomplete. To tackle this problem, here we have investigated the evolutionary dynamics of the potyvirus multi-functional protein HC-Pro, with particular focus on its functional domains. The protein was partitioned into the three previously described functional domains and each domain was analyzed separately and assembled. We searched for signatures of adaptive evolution and evolutionary dependencies of amino acid sites within and between the three domains using the entire set of available potyvirus sequences in GenBank. Interestingly, we identified strongly significant patterns of co-occurrence of adaptive events along the phylogenetic tree in the three domains. These patterns suggest that Domain I, whose main function is to mediate aphid transmission, has likely been coevolving with the other two domains, which are involved in different functions but all requiring the capacity to bind RNA. By contrast, episodes of positive selection on Domains II and III did not correlate, reflecting a tradeoff between their evolvability and their evolutionary dependency likely resulting from their functional overlap. Covariation analyses have identified several groups of amino acids with evidence of concerted variation within each domain, but inter-domain significant covariations were only found for Domains II and III, further reflecting their functional overlapping.