Genomics stratification and differential natural selection signatures among the human Norovirus genogroup-II isolates

Abstract The Norovirus (NoV) from the family Caliciviridae is the most common cause of gastroenteritis diseases in human. There are ten NoV genogroups are reported so far. Among these, the genogroup II (GII) is commonly prevalent and causes serious infection worldwide. The complete genome sequences of NoV GII isolates from different continental origin were retrieved from the public database. The model-based clustering approach implemented in the STRUCTURE resource was employed for assessment of genetic composition. The Mega-X and IQ tree were tools used for phylogenetic analyses. Genome-wide natural selection analyses were pursued via the maximum likelihood based methods. The demography features of NoV GII genome sequences were assessed using the BEAST package. All the NoV GII sequences initially clustered into two main subpopulations at significant K=2. The genotype GII.4 samples clearly split from the rest of all the genotypes. This indicate marked genetic distinction between norovirus GII.4 and non-GII.4 samples. The phylogenetic analyses depicted five distinct sub-clades for genotype GII.2 and seven sub-clades for GII.4 samples, speculate about the emergence of new lineages from these genotypes. Several isolates with admixed ancestry were identified, that constituted distinct sub-clusters. No continental-specific genetic distinction was observed among the NoV GII isolates. Significant genomic signatures of both positive and negative natural selection were identified across the NoV GII genes. Differential pattern of positive selection signal inferred between the GII.4 and non-GII.4 genotypes. The demographic analyses unveiled a rise in effective population size of NoV GII during 2009-2010, followed by a rapid fall in 2015.