The 3′ untranslated region of tick-borne flaviviruses originated by the duplication of long repeat sequences within the open reading frame

Comparative alignment of the 3′untranslated regions (3′UTRs) of tick-borne flaviviruses has previously revealed short direct repeat sequences about 25–70 nucleotides long [Gritsun, T.S., Venugopal, K., Zanotto, P.M., Mikhailov, M.V., Sall, A.A., Holmes, E.C., Polkinghorne, I., Frolova, T.V., Pogodina, V.V., Lashkevich, V.A., Gould, E.A., 1997. Complete sequence of two tick-borne flaviviruses isolated from Siberia and the UK: analysis and significance of the 5′ and 3′-UTRs. Virus Res. 49 (1) 27–39; Wallner, G., Mandl, C.W., Kunz, C., Heinz, F.X., 1995. The flavivirus 3′-noncoding region: extensive size heterogeneity independent of evolutionary relationships among strains of tick-borne encephalitis virus. Virology, 213 (1) 169–178]. We now show that these short sequences appear to have originated from longer repeat sequences (LRSs) that are present both in the 3′UTR and the open reading frame of the genome. We propose that the 3′UTR, and possibly the open reading frame, evolved through multiple duplications, deletions and mutations of a primordial sequence element.