Molecular instability of the mitochondrial haplogroup T sequences at nucleotide positions 16292 and 16296

The mitochondrial haplogroup T, characterized by bile nucleotide motif 1612 6C 16294T in the hypervariable segment I (HVS I), is one of the most freque nt among Europeans. It has been shown that this: haplogroup includes the on ly well-resolved subgroup, T1, but that other HVS I sequences cannot be dif ferentiated into subgroups due tu possible homoplasies at nucleotide positi ons 16292, 16296 and 16304, leading to the reticulations in the topology of phylogenetic networks. To study the problem of molecular instability at th ese positions, we have performed an analysis of 159 previously published We st Eurasian HVS I sequences belonging to haplogroup, T, together with 12 ne w HPS I sequences of Eastern Slavs. These 12 sequences represent 16.9% of a total of 71 samples analysed and identified as haplogroup T mtDNAs by RFLP analysis in this study. A search for rare point mutations associated with differently combinations of nucleotides 16292T, 16296T and 16304C within th e haplogroup T sequences, and specific to certain populations or a group of closely related-by-descent populations. was performed. This analysis revea led 11 marker mutations, each of which was characteristic fur a certain gro up of linguistically or geographic ally close individuals - the Adygei, Ger mans, Kazakhs and linguistic isolates of the Eastern Italian Alps. The occu rrence of these rare population-specific polymorphisms in association with various combinations of mutations at positions 16292 and 16296 on the haplo group T background provides evidence of molecular instability at these nucl eotide positions. Molecular instability in the haplogroup T HVS I sequences is also suggested by multiple independent losses of the haplogroup, T diag nostic nucleotide variants in different populations. The results of the pre sent study suggest that identical haplogroup T HVS I sequence types might h ave arisen independently in different human populations.