Co-evolving pairs of complementary nucleotide sequence regions as candidates for bundling signals in viruses with segmented genomes

Some of RNA viruses with segmented genomes are believed to undergo selective packaging, in which one copy of each genomic segment is incorporated into a virion. The selective packaging is thought to be mediated by supra-molecular complex formation of genomic RNA segments through inter-segmental base pairing of complementary nucleotide sequence regions termed the bundling signal. Here the nucleotide sequences of 10 genomic segments (large: L1, L2, and L3; medium: M1, M2, and M3; and small: S1, S2, S3, and S4) for 29 avian (ARV) and 8 pteropine (PRV) orthoreovirus isolates were analyzed to identify co-evolving pairs of complementary nucleotide sequence regions within and between genomic segments. The co-evolving pairs within and between genomic segments were predicted to be involved in intra-segmental and inter-segmental interactions, respectively. One co-evolving pair each was identified within M1 and S3, and both pairs indeed tended to constitute stems in the intra-segmental RNA secondary structures. In addition, one co-evolving pair each was identified between S3 and S4, L2 and S4, and L3 and M1, and the co-evolving pair between S3 and S4 tended to constitute loops in the intra-segmental RNA secondary structures. The co-evolving pair identified between S3 and S4 was considered as a candidate for the bundling signal in ARV and PRV.