Full length genomes of genotype IIIA Hepatitis A Virus strains (1995-2008) from India and estimates of the evolutionary rates and ages

Abstract

With the changing epidemiology, outbreaks of Hepatitis A Virus (HAV) have been reported from different parts of India. To characterize HAV strains circulating in India (1995-2008), 6 full genome sequences of the predominant genotype, IIIA, were determined. Further, applying the Bayesian Markov Chain Monte Carlo (MCMC) framework to the full genomes of Indian HAV strains as well as other global strains (human as well as simian), we derived the mean nucleotide substitution rate and evolutionary timescales with emphasis on the age of genotype III and IIIA strains. The genomic length of all the 6 HAV isolates was 7464 nt excluding the poly A tract. Phylogenetic analysis confirmed that all the Indian isolates were close to Nor-21 (AJ299464) and HMH (AY644337) of subgenotype IIIA. The ORF of the isolates when compared within genotype III at amino acid level showed a highly conserved pattern. Under the best fit expansion population relaxed molecular clock model, the estimated mean substitution rate of the HAV full genomes (human and simian strains) was 1.73×10⁻⁴ substitutions/site/year based on which the earliest transmission of HAV from simian to humans is estimated to have occurred about 3564 years ago. The mean substitution rate within human HAV full genomes under the same model was estimated to be 1.99×10⁻⁴ substitutions/site/year. With this the mean age of genotype III strains was estimated to be 592 years while that of genotype IIIA was estimated to be 202 years. The time to the most common recent ancestor (tMRCA) of the Indian genotype IIIA isolates was calculated to be 116 years.