Nucleotide sequence variability of whole mitochondrial genomes (mtDNA) was analyzed and mutation spectra were reconstructed (by L-chain of mtDNA) in four regional groups of indigenous populations representing Northeastern and Southern Siberia, Western Asia, and the Americas. The pyrimidine transitions were found to be predominant in all groups; of these, the T→C substitutions were most frequent. The second most common in all regional groups (except Northeastern Siberia) are A→G substitutions. Of the transversions, in all the populations studied the C→A substitutions dominate. Between-regional differences in the distribution of nucleotide substitutions in mtDNA mutation spectra were not detected. However, a significant (4-fold) decrease in the number of mutations in mitochondrial gene pools was detected in the indigenous population of Northeastern Siberia compared to other regions. This may be due to the increased effect of negative selection on mtDNA in the Far North environment, which prevents the accumulation of new mutations, and genetic drift, which is most pronounced in isolated and small populations of Northeastern Siberia. Because of the lack of between-regional differences in mtDNA mutation spectra, the results we obtained do not allow us to confirm the hypothesis that the T→C substitution frequency is a molecular marker of the level of oxidative stress in mitochondria (at least for germline mutations).