Similarity of Human Mitochondrial DNA Nucleotide Substitution Spectra Reconstructed over One and Many Generations

Abstract—Using phylogenetic analysis of mitochondrial whole genome nucleotide sequences (mtDNA), which allows the study of genetic changes over many generations, a spectrum of nucleotide substitutions (along the L-strand of mtDNA) was reconstructed in European populations. The spectra of mtDNA nucleotide substitutions observed in a heteroplasmic state (at the ≥1 and ≥5% levels) in first generation children were also analyzed. It was found that the spectra of nucleotide substitutions reconstructed over one and many generations practically do not differ in their main parameters: the distribution of pyrimidine and purine substitutions (with predominance of T→C transitions) and the ratio of the number of transitions and transversions. Analysis of the phylogenetic tree of mtDNA haplotypes in Europeans clearly revealed the influence of negative (purifying) selection on mitochondrial gene pools. It is suggested that the selective processes guiding the mtDNA evolution in one and many generations are of a similar nature, i.e., are caused by negative selection. The problem of how mutations occur and spread in mitochondria of germ line cells is discussed.