Molecular dating of FMDVs. Regression analyses of root-to-tip genetic distance (s) and sampling dates (t) were performed for the five genomic regions to evaluate their temporal signals (A). The solid lines are models estimated based on the entire dataset. The dotted lines are models estimated without outliers (red dots). P-values are reported next to the equations. Analyses suggested only the P1 and 3D regions had sufficient temporal signals for molecular dating (p values of the slopes < 0.05). Evolutionary timescales of FMDVs were computed by using the relationships between s and t estimated base on the P1 (B) and 3D (C) regions. Confidence intervals of the estimated dates are shown by the horizontal bars; grey: tMRCA of all FMDVs, green: tMRCA of Euro-Asiatic serotypes, orange: tMRCA of SAT serotypes, purple; others. Corresponding date estimates by other studies are shown for comparison (Top). The numbers on nodes are median date estimates and their associated confidence intervals. Coloured background and vertical line indicate historical events that might be relevant in the global transmission of FMDVs. The “sailboat” symbol: the rise of livestock transportation from the Mediterranean region to Northern Europe in the thirteenth century35; the green “book” symbol: early symptomatic record of FMD in Italy in 151434; the orange “book” symbol: early symptomatic record of FMD in Africa in 179543; the “ship” symbol: the age of discovery starting around early fifteenth century to mid-seventeenth century. Ship and book drawings were Microsoft PowerPoint ClipArts.