Early origin and global colonisation of foot-and-mouth disease virus

Figure 1. Recombination analysis. (Top) schematic diagrams of FMDV’s ORF. The polyprotein encoded by the ORF is processed into several protein products by proteases (Diamonds; see Keys for the names of proteases). Based on the functions of mature proteins, the ORF can be divided into four main functional areas (L: turquoise; P1: red; P2: green; and P3: blue). L region encodes a leader protease (Lpro). The P1 region encodes four structural capsid proteins, VP1–4. The P2 and P3 regions encode several non-structure proteins, including 2A–C, and 3A–D. 3C and 3D are a viral protease (3Cpro) and an RNA-dependent RNA polymerase (3Dpol), respectively. (Bottom) number of inferred recombination breakpoints estimated per 200-nucleotide window. The tick marks above the plot show the locations of individual breakpoints inferred. Global and local 99% and 95% confidence intervals of the estimated recombination breakpoints are shown (see Keys). Regions with the inferred number of recombination breakpoints more than the 99% local confidence intervals are considered recombination hotspots. Four recombination hotspots were detected in total, indicated by vertical transparent strips. Vertical dotted lines are…

Figure 2. FMDV phylogenies. Five phylogenies were estimated from the five recombination-free alignments (A: P1; B: Lpro; C: P2; D: 3A–C; and E: 3D) under the maximum likelihood framework. The numbers on nodes are bootstrap clade support values, shown for various distinct clades. Serotype (S) and geographical (G) information were mapped onto the trees (see Keys). Scale bars are in the units of nucleotide substitutions per site. The map (licence CC BY-SA 4.0) was created with mapchart.net.

Figure 3. 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…

Figure 4. An updated hypothesis on the global colonisation of FMDV. The ancestor of Euro-Asiatic FMDV strains likely originated in the Mediterranean region, and spread to Europe, facilitated by the raise in goods and livestock transportation from the Mediterranean countries to Northern Europe between the thirteenth and fifteenth century. The foundation for the European global trade between Europe and the rest of the world was laid during the Age of Discovery (fifteenth–seventeenth century), and this likely helped the disease to disperse from Europe to Asia. The cattle shipment by European immigrants from Europe to Argentina in the late 1860s was likely responsible for the emergence of FMD in the South America continent. The SAT strains, on the other hand, are very well confined to the African continent. They likely have been circulating in wild and farm African animals for a long time, which play an important part in maintenance of the disease in the African continent. It is unclear, however, if the disease itself was first developed in the African continent then spread to Mediterranean countries (dotted upward arrow) or the other way around (dotted downward arrow). Further studies are…