Revisiting the clinal concept of evolution and dispersal for the tick-borne flaviviruses by using phylogenetic and biogeographic analyses

Abstract

Tick-borne flaviviruses (TBF) are widely dispersed across Africa, Europe, Asia, Oceania, and North America, and some present a significant threat to human health. Seminal studies on tick-borne encephalitis viruses (TBEV), based on partial envelope gene sequences, predicted a westward clinal pattern of evolution and dispersal across northern Eurasia, terminating in the British Isles. We tested this hypothesis using all available full-length open reading frame (ORF) TBF sequences. Phylogenetic analysis was consistent with current reports. However, linear and nonlinear regression analysis of genetic versus geographic distance combined with BEAST analysis identified two separate clines, suggesting that TBEV spread both east and west from a central point. In addition, BEAST analysis suggested that TBF emerged and dispersed more than 16,000 years ago, significantly earlier than previously predicted. Thus, climatic and ecological changes may have played a greater role in TBF dispersal than humans.

Fig 1

Maximum clade credibility tree of the tick-borne flaviviruses. The node labels indicate the tMRCA, with the 95% HPD in parentheses. All nodes labeled with the tMRCA had a posterior probability of 1 (data not shown). Strains are labeled as strain name_year of collection.

Fig 2

Genetic versus geographic distance between viral isolates was plotted for POWV LB (A), OHFV Guriev (B and C), and TBEV Sofjin-HO (D, E, and F). Linear and nonlinear regression lines are shown where calculated. For regression, Russian POWV isolates were removed from relevant analyses (A, C, and F).

Fig 3

Possible model for TBF dispersal. The maximum clade credibility tree was manually plotted onto geographic space showing the most parsimonious route of dispersal for these viruses based on all complete genomic sequences. Approximate tMRCA dates are shown at all major nodes in the tree.