The origin of European and North American infectious salmon anemia virus (ISAV) revisited by relaxed molecular clock analysis

Abstract

An emerging infectious disease, called infectious salmon anemia (ISA), among farmed salmon has raised the concern of its impact on salmon-farming industry. The causative agent was identified to be a segmented RNA virus and named as infectious salmon anemia virus (ISAV). Earlier phylogenetic analyses classified the ISAV, predominating in European and North American aquacultural farms separately, into two genetically distinct strains: European (EU) and North American (NA) type. It was suggested that human traffic and trading have transported their common ancestor between these continents, and led to their local emergences. A recent evolutionary study on ISAV hemagglutinin-esterase (HE) and fusion protein (FP) gene suggested, under global molecular clock assumption, atypically low substitution rates (106 and 105 substitutions/site/year, respectively) comparing to other RNA viruses. This result has new implications on the viral epidemiology and the hypothesis of origin: EU and NA isolates may have separated long before any human traffic could transport the virus. We examined the genetic sequences of HE gene from both EU and NA strains of ISAV. Our result demonstrated a large disparity of the substitution rates with in the phylogeny, which disrupted the molecular clock assumption, was caused by the presence of a small group of virus isolates with extremely low rate. The presence of these isolates in the phylogeny can mislead the substitution rate estimation in global clock analysis. By using relaxed molecular clock models implemented in the Bayesian framework which accommodating the rate variation, the time of the most recent common ancestor of EU and NA strains was extrapolated to around 300 years ago. This finding reasserts the original hypothesis suggesting the translocation of ancient ISAV between North America and Europe could be a consequence of human cross-ocean traffic and trading, which had been refuted by the recent global clock analysis.