Recombination patterns in aphthoviruses mirror those found in other picornaviruses

Abstract

Foot-and-mouth disease virus (FMDV) is thought to evolve largely through genetic drift driven by the inherently error-prone nature of its RNA polymerase. There is, however, increasing evidence that recombination is an important mechanism in the evolution of these and other related picornoviruses. Here, we use an extensive set of recombination detection methods to identify 86 unique potential recombination events among 125 publicly available FMDV complete genome sequences. The large number of events detected between members of different serotypes suggests that horizontal flow of sequences among the serotypes is relatively common and does not incur severe fitness costs. Interestingly, the distribution of recombination breakpoints was found to be largely nonrandom. Whereas there are clear breakpoint cold spots within the structural genes, two statistically significant hot spots precisely separate these from the nonstructural genes. Very similar breakpoint distributions were found for other picornovirus species in the genera Enterovirus and Teschovirus. Our results suggest that genome regions encoding the structural proteins of both FMDV and other picornaviruses are functionally interchangeable modules, supporting recent proposals that the structural and nonstructural coding regions of the picornaviruses are evolving largely independently of one another.

FIG. 1.

(a) Phylogenetic compatibility matrix of 125 FMDVs. To generate this plot, a 300-nucleotide window was moved across the alignment with 100-nucleotide steps, and at each position, a neighbor-joining tree was constructed. The compatibility of two trees is measured by the number of phylogenetic violations that are required to match the ordering of taxa within the tree. Obtained values are color coded, with phylogenetically compatible regions shown in blue. The FMDV genome diagram superimposed on the diagonal axis was drawn to scale relative to FMDV A10/Holland/62 (AY539751). (b) Potential recombination breakpoint hot spots within the FMDV alignment. Detectable breakpoint positions are indicated by small vertical lines at the top of the graph. A 200-nucleotide window was moved along the alignment 1 nucleotide at a time, and the breakpoints detected within the window region were counted and plotted (solid line). The upper and lower broken lines, respectively, indicate 99% and 95% confidence thresholds for globally significant breakpoint clusters. The light- and dark-gray areas, respectively, indicate local 99% and 95% breakpoint-clustering thresholds, taking into account local regional differences in sequence diversity that influence the abilities of different methods to detect recombination breakpoints (for a detailed description of the permutation test, see http://darwin.uvigo.es/rdp/heath2006.zip).

FIG. 2.

Phylogenetic-compatibility matrices and breakpoint density plots of enteroviruses and teschoviruses constructed as outlined for Fig. 1. (a) Enterovirus species A. (b) Enterovirus species B. (c) Enterovirus species C. (d) Teschoviruses. The superimposed genome diagrams were drawn to scale relative to sequences NC001430, NC001472, NC002058, and AJ011380. The upper and lower broken lines in each breakpoint density graph, respectively, indicate 99% and 95% confidence thresholds for globally significant breakpoint clusters. The light- and dark-gray areas, respectively, indicate local 99% and 95% breakpoint-clustering thresholds, taking into account regional differences in sequence diversity that influence the abilities of different methods to detect recombination breakpoints (http://darwin.uvigo.es/rdp/heath2006.zip). It should be noted that apart from a different color scale, the phylogenetic-compatibility analyses presented in panels a, b, and c are a repeat of those, using the same datasets, previously described by Simmonds and Welch (29) and are included here for comparative purposes.