Direct repeats in the flavivirus 3′ untranslated region; a strategy for survival in the environment?

Previously, direct repeats (DRs) of 20–70 nucleotides were identified in the 3′ untranslated regions (3′UTR) of flavivirus sequences. To address their functional significance, we have manually generated a pan-flavivirus 3′UTR alignment and correlated it with the corresponding predicted RNA secondary structures. This approach revealed that intra-group-conserved DRs evolved from six long repeated sequences (LRSs) which, as ∼ 200-nucleotide domains were preserved only in the genomes of the slowly evolving tick-borne flaviviruses. We propose that short DRs represent the evolutionary remnants of LRSs rather than distinct molecular duplications. The relevance of DRs to virus replication enhancer function, and thus survival, is discussed.