ИСТИНА

Introduction: Non-polio enteroviruses are a ubiquitous and rapidly evolving group of non-enveloped RNA viruses and an important source of emerging infections. The genus Enterovirus comprises more than 100 types, and novel types are regularly reported; however, the mechanisms of their emergence remain unclear. We performed phylogenetic analysis of the most common enteroviruses types to investigate the general trends in the evolution of capsid protein VP1. Methods: We analyzed 33 types represented by more than 35 non-redundant partial VP1 sequences in GenBank in parallel using Bayesian phylogenetic approach implemented in BEAST software. Results: Inferred substitution rates in non-polio enteroviruses were in the range of 0.41-10-2 to 3.07-10-2 substitutions per site per year. The age of most recent common ancestors of known isolates of each type was 55-200 years ago. The topology of inferred phylogenetic trees suggested that global populations of VP1 sequences underwent global-scale bottlenecks, which resulted in the extinction of most lineages that hypothetically existed in the middle of the 20th century and could repeatedly reset the common ancestor dates. Nevertheless, the species-level analysis suggested that diversification of contemporary types occurred within the last 600 years. The analysis of 2657 complete VP1 sequences of 33 types indicated that the type criterion based upon 75% nucleotide sequence identity remains generally valid, despite a high substitution rate and the exponential growth of the number of sequenced isolates. Conclusion: The population of VP1 genes of most enterovirus types underwent global expansion-extinction cycles, which are one of the main driving forces of enterovirus evolution. Despite the high rate of mutation fixation, the types remain stable on the scale of decades; this suggests a hypothesis that enterovirus types correspond to fitness peaks, where the global population wanders around.