Molecular Evolution of Viruses

Molecular evolution is the process of evolution at the scale of DNA, RNA and proteins. Our goal was to study molecular evolution of viruses with special reference to Influenza A Virus. The recent Influenza A/H1N1(2009) outbreak has been the focus of intense research because of its high level of infectivity across the globe. Analysis of nucleotide sequence polymorphism in the genomic segments encoding the two most immunologically important proteins of influenza A, neuraminidase (NA) and hemagglutinin (HA), showed that the H1N1 (2009) has resulted from the spread of an HA segment of recent origin and low diversity through a population of ancient and much more diverse NA segments. We also studied about the selection pattern of CTL epitope and CTL non-epitope regions of different proteins of Influenza and found that natural selection is the main pattern of selection with epitope regions being more conserved than non-epitope regions. This dissertation also focuses on implementation of a methodology to study phylogeny of viral protein sequences based on a technique called chaos game representation. Here we present a method for using CGR to explore evolutionary relationships of protein sequences based on amino acid properties and illustrate the approach with complete sets of protein translations from viral genomes. In an analysis of complete polyprotein sequences from the viral family Flaviviridae, the CGR method was able to cluster members of major viral groups together, but relations within groups were not well resolved in comparison to an alignment-based phylogeny. We applied the method to members of five different families of ssRNA positive-strand viruses, and each family formed a distinct cluster. We also present a method of testing the reliability of clustering in CGR-based trees, which involves the use of multiple random starting points for the CGR process