An Extensive Analysis of Codon Usage Pattern, Evolutionary Rate and Phylogeographic Reconstruction in Foot and Mouth Disease (fmd) Serotypes (a, Asia 1 and O) of Six Major Climatic Zones of India: A Comparative Study

Foot and mouth disease (FMD) is a major economically important viral disease of cloven-hoofed livestock globally. The FMD virus (FMDV) spreads widely in confined, cool, and humid climatic conditions. Being an RNA virus, FMDV is genetically unstable, and its genome evolution is highly influenced by mutational pressure. The climatic and environmental conditions have a significant impact on mutational pressure. The present study is a primary effort to establish a comprehensive relationship between climatic factors and the molecular evolutionary pattern of serotypes FMDV circulating in India. In this study, isolates of three serotypes (A, Asia 1, and O) were selected from six major climatic zones of India (Montane, Humid subtropical, Tropical wet and dry, Tropical wet, Semi-arid and Arid). Based on the full genome nucleotide sequence data, the codon usage bias, evolutionary and phylogeographic analysis was carried out. The study revealed that the codon use bias indicators in the FMDV serotypes differed significantly depending on the climatic zones. It implies that the selection and mutational pressure influence the codon usage pattern indices, with mutational pressure taking precedence in determining the codon usage bias of the FMDV genome. The tMRCA was estimated to be 1977, 1956, and 1953 for Indian FMD virus serotype-A, Asia 1, and O respectively which is around 32, 60, and 61 years before its actual identification in the field. Based on the evolutionary rates the serotype O is evolving rapidly compare to other serotypes in India. Virus transmission across the region was evident from the phylogeographic analysis. The integrated analysis of codon usage bias, evolutionary rate, and phylogeography analysis signifies the major role of mutational and selection pressure, implying that the FMD virus co-evolution and adaptations are highly influenced by climatic/environmental factors.