The flavivirus 3'-noncoding region: extensive size heterogeneity independent of evolutionary relationships among strains of tick-borne encephalitis virus.

The sequences of the 3'-noncoding regions (NCR) of 12 strains of tick-borne encephalitis (TBE) virus were analyzed and found to vary in length from 350 to approximately 750 nucleotides. The size heterogeneity is restricted to a variable region following the stop codon, whereas the most 3'-terminal 350 nucleotides form a highly conserved core element containing several potentially important sequence motifs and secondary structure elements. A homoadenosine tract previously thought to form the 3'-terminus of some TBE virus strains was now shown to be an internal part of the variable region of certain strains. The strains included in this study were isolated from both humans and ticks over a time period of more than 40 years at various locations throughout the entire endemic area of TBE virus, but there was no correlation between these parameters and the observed lengths of the 3'-NCRs. Identity data calculated from common 3'-NCR sequences and also from short sections of the open reading frame indicated that coding and noncoding sequences were linked during evolution, but the lengths of the 3'-NCRs were independent of these relationships. These observations together with detailed analyses and alignments of the sequences suggest that the variable region was originally acquired through duplication and recombination events, but--much more recently during evolution--various portions of this region were lost again, resulting in the now observed heterogeneous 3'-NCRs.