Phylogenetic classification of TT virus groups based on the N22 region is unreliable

Evolutionary studies on the recently discovered TT virus (TTV) are currently focused on approximately 220 nts of the N22 region, since this is the region for which most sequence information is available. Regarding the extensive sequence heterogeneity in this region, within group classification can be sufficiently reliable, however, between group classification becomes problematic. We observed high divergence at the nucleotide level between distant related strains (TTV groups) preventing unambiguous alignments, saturation in transitions within TTV groups and considerable phylogenetic noise due to conflicting signals within distinct genotypes. Consequently, analysing all TTV groups in one tree, using this 220 nt region provides unreliable results. Also within genotype analysis can produce conflicting results. On the other hand, this region is still suitable to some extent for within TTV group phylogenetic analysis. We suggest that care should be taken in future TTV phylogenetic analysis, in particular, larger and more conserved regions should be sequenced to allow between group comparisons.