Evolution of complementary nucleotides in 5' and 3' untranslated regions of influenza A virus genomic segments.

The genome of influenza A virus comprises 8 segments (segments 1-8) of single-stranded RNA (virion RNA: vRNA) with negative-polarity. All vRNAs share 13 and 12 terminal nucleotides in the 5' and 3' untranslated regions (UTRs), respectively, which are partially complementary and constitute panhandle and corkscrew structures. Here, it is shown, from the analysis of genomic sequences for 506 strains of influenza A virus, that the number of contiguous complementary nucleotides in the 5' and 3' UTRs varies from 4 to 7 among segments. Complementary nucleotides were segment specific and highly conserved in all segments except for segment 6, where in the phylogenetic analysis co-evolution was observed to have occurred between and within subtypes of neuraminidase (NA). Mutations in the terminal sequences sometimes appeared to have caused convergence between subtypes, involving changes in multiple nucleotide positions. These observations suggest that intra-segmental (homologous) recombinations may have taken place for transferring terminal sequences in segment 6.