Abstract
Comparative complete genome analyses were conducted on 173 field outbreak strains of foot-and-mouth disease virus (FMDV) serotype A, collected from various regions worldwide, including strains that have circulated in India in recent years. Phylogenetic analyses revealed that the majority of isolates included in this study belonged to the Asia (n = 108), followed by EURO-SA (n = 41) and Africa (n = 24) topotypes. The mean rate of evolutionary change in FMDV serotype A was estimated to be 2.369 × 10-3 substitutions/site/year for the Open Reading Frame (ORF). Faster substitution rates in the Asia topotype suggests heightened selective pressures, likely driven by pre-existing host immune responses due to prior infections or vaccination. The periodic emergence and subsequent dominance of notable genotypes or lineages within the Asia topotype such as genotype 18 (ASIA/VII), genotype 20 (Sea-97), and genotype 26 (Iran-05) underscore the ongoing diversification, adaptation, and selection of the virus in the field across Asia. Monophyletic clustering within the Asia and Africa topotypes suggests region-specific evolutionary trajectories, while the diversity observed within EURO-SA indicates an older and more genetically varied lineage pattern. The presence of amino acid insertions and deletions in some of the isolates points to potential hotspots for genetic change, particularly in regions such as L, VP1, and 3A, reflecting high genetic volatility. Positive selection across the protein-coding regions excluding VP4 and 2A highlights the virus's adaptive potential, likely contributing to immune evasion, host adaptation, and enhanced fitness for replication and transmission. Evidence of recombination events, particularly in five isolates with spatio-temporal overlaps, indicates dynamic viral evolution potentially favourable for emergence of new variants. These findings are crucial for understanding foot-and-mouth disease (FMD) epidemiology and may have implications for global FMD control strategies.