A procedure for detecting selection in highly variable viral genomes: evidence of positive selection in antigenic regions of capsid protein VP1 of foot-and-mouth disease virus.

A new procedure is described for the detection of positive selection among sequences of viral proteins from highly variable viruses. The approach is based on the estimation of the rates of nonsynonymous to synonymous (ns/s) mutations to the overall genetic distances amongst the sequences compared. Rates of ns/s substitutions were calculated, and the individual profiles were arranged as a function of the genetic distance observed between the complete sequences. The resulting surfaces allowed identification of protein regions whose rates of ns/s substitutions were consistent with the existence of positive selection. This procedure has been applied to the study of a highly variable antigenic protein, VP1, a protein present in foot-and-mouth disease virus (FMDV). The analysis of groups of VP1 sequences corresponding to FMDV serotypes A, O and C, resulted in the identification of two regions, which contribute to an important antigenic site, where positive selection appears to operate.