Evidence for positive selection in foot-and-mouth disease virus capsid genes from field isolates

The nature of selection on capsid genes of foot-and-mouth disease virus (FM DV)was characterized by examining the ratio of nonsynonymous to synonymous substitutions in 11 data sets of sequences obtained from six different sero types of FMDV. Using a method of analysis that assigns each codon position to one of a number of estimated values of nonspnonymous to synonymous ratio , significant evidence of positive selection was identified in 5 data sets, operating at 1-7% of codon positions. Evidence of positive selection was i dentified in complete capsid sequences of serotypes A and C and in VP1 sequ ences of serotypes SAT 1 and 2. Sequences of serotype SAT-2 recovered from a persistently infected African buffalo also revealed evidence for positive selection. Locations of codons under positive selection coincide closely w ith those of antigenic sites previously identified with the use of monoclon al antibody escape mutants. The vast majority of codons are under mild to s trong purifying selection. However, these results suggest that arising anti genic variants benefit from a selective advantage in their interaction with the immune system, either during the course of an infection or in transmis sion to individuals with previous exposure to antigen. Analysis of amino ac id usage at sites under positive selection indicates that this selective ad vantage can be conferred by amino acid substitutions that share physicochem ically similar properties.