Abstract
Recurrent outbreaks of senecavirus A (SVA)-associated vesicular disease have led to a large number of infected pigs being culled and has caused considerable economic losses to the swine industry. Although SVA was discovered 2 decades ago, knowledge about the evolutionary and transmission histories of SVA remains unclear. Herein, we performed an integrated analysis of the recombination, phylogeny, selection, and spatiotemporal dynamics of SVA. Phylogenetic analysis demonstrated that SVA diverged into two main branches, clade I (pre-2007 strains) and clade II (post-2007 strains). Importantly, analysis of selective strength showed that clade II was evolving under relaxed selection compared with clade I. Positive selection analysis identified 27 positive selective sites, most of which are located on the outer surface of capsid protomer or on the important functional domains of nonstructure proteins. Bayesian phylodynamics suggested that the estimated time to the most recent common ancestor of SVA was around 1986, and the estimated substitution rate of SVA was 3.3522 × 10(-3) nucleotide substitutions/site/year. Demographic history analysis revealed that the effective population size of SVA has experienced a gradually increasing trend with slight fluctuation until 2017 followed by a sharp decline. Notably, Bayesian phylogeographic analysis inferred that Brazil might be the source of SVA's global transmission since 2015. In summary, these data illustrated that the ongoing evolution of SVA drove the lineage-specific innovation and potentially phenotypically important variation. Our study sheds new light on the fundamental understanding of SVA evolution and spread history. IMPORTANCE Recurrent outbreaks and global epidemics of senecavirus A-associated vesicular disease have caused heavy economic losses and have threatened the development of the pig industry. However, the question of where the virus comes from has been one of the biggest puzzles due to the stealthy nature of the virus. Consequently, tracing the source, evolution, and transmission pattern of SVA is a very challenging task. Based on the most comprehensive analysis, we revealed the origin time, rapid evolution, epidemic dynamics, and selection of SVA. We observed two main genetic branches, clade I (pre-2007 strains) and clade II (post-2007 strains), and described the epidemiological patterns of SVA in different countries. We also first identified Brazil as the source of SVA's global transmission since 2015. Findings in this study provide important implications for the control and prevention of the virus.