Variation of human mitochondrial DNA: distribution of hot spots in hypervariable segment I of the major noncoding region

Abstract

Mitochondrial DNA (mtDNA) samples belonging to fifteen phylogenetically related mtDNA types specific to the populations of Europe (H, V, J, T, U, K, I, W, and X) and Northern Asia (A, C, D, G, Y, and Z) were typed for sequence variation in hypervariable segment I (HVSI). The approach used allowed to distinguish several hypervariable sites at nucleotide positions 16093, 16129, 16189, 16311, and 16362. Identical mutations at these sites were found in 10-11 out of 15 mtDNA groups examined. Positions 16126, 16172, 16192, 16256, 16261, 16291, 16293, and 16298 appeared to be less variable, since parallel mutations at these sites were found in 6-8 European and Asian mtDNA groups. The examples of the effects of mutations in hypervariable positions at the major noncoding mtDNA region on the frequency of reverse mutations in other mtDNA regions are presented. It was shown that such effects of nucleotide context on the mutation rate could be observed in phylogenetic mtDNA networks such as cyclic structures like rhombs and cubes. Analogous structures in the networks could be seen also in the case of the appearance of recombinant mtDNA types resulted from homologous recombination between mtDNA molecules in heteroplasmic mixture. The problem of the effect of polynucleotide context on the intensity of mtDNA mutagenesis is discussed. Recombination processes along with site-directed mutagenesis caused by action of genetic factors (of nuclear genome) and/or of the environment are considered as possible mechanisms of mitochondrial genome evolution.