A phylogenetic approach to detecting reassortments in viruses with segmented genomes

When multiple strains of viruses with segmented genomes co-infect a single cell, strains with novel genomic constellations may be created. This mutational process, called reassortment, has caused pandemics of influenza A virus in 1957 and 1968. Here a phylogenetic approach to detecting reassortments, which can be used even when the phylogenetic tree constructed for all strains analyzed is unreliable, is presented. A quartet of strains is examined at a time, where a phylogenetic tree is constructed for each genomic segment and the topology is compared among segments only when all quartet trees are supported with a statistical significance. The occurrence of reassortment and the segments involved in the reassortment event are inferred according to the pattern of topological difference among segments. The reassortment point for a pattern is inferred by superimposing the exterior branches of relevant quartet trees on the all-strains trees. In the analysis of H1N1 and H3N2 human influenza A viruses, a topological difference was observed for all pairs of genomic segments, suggesting that there is no pair of segments that has always co-segregated in reassortment during the evolutionary history of these viruses. When the reassortment point was inferred for the pattern of topological difference that was supported with the largest number of quartets for each virus, the results appeared to be mostly correct, suggesting that the method was largely reliable.