Analysis of the leader proteinase (L(pro)) region of type A foot-and-mouth disease virus with due emphasis on phylogeny and evolution of the emerging VP3(59)-deletion lineage from India.

Genotype inclusive grouping of Indian type A isolates as observed in 1D region based phylogeny was distorted at complete L(pro) region, where the VP3(59)-deletion group lineages of genotype VII clustered away from both genotypes VII and VI, confirming its uniqueness and independent evolution of L(pro) and 1D region. Akin to the 1D region, this deletion group is gradually diverging genetically even at L region forming more number of lineages and inter-lineage distance at L region is considerably more than that for 1D region. The deletion group is restricted to India only as none of the exotic sequences clustered within this group. Notably, L protein exhibited variability comparable to external capsid proteins as evident from its high d(N)/d(S) ratio (0.105), number of variable amino acid positions (41%), low Ts/Tv ratio (3.47) and alignment revealed N-terminal region, beta2 sheet and C-terminal extension to be extremely variable. Basic residues at P1, P3 and only leucine at P2 were predicted to provide an optimum autocatalytic cleavage site at L/P1 junction. All of the eight sites identified to be under positive selection revealed aa substitutions of varied physicochemical properties and at two positions lineage specific signatures were observed, which supports the contention that lineages are evolving under differential selection pressure to adapt to the varied ecological environment.