The uniparentally inherited mtDNA can only change by sequential accumulation of mutations along radiating female lineages. Therefore, the mtDNA mutational tree and ancient migrations of women were reconstructed by sequencing mtDNAs from indigenous populations and correlating their regional clusters of related haplotypes (haplogroups) with the population’s geographic location. The haplogroups are regional because they were founded by regionally adaptive functional variants. The mtDNA tree originates in Africa, and all African mtDNAs are classified together as macrohaplogroup L. From haplogroup L3, two mtDNA lineages, M and N, arose in Ethiopia and successfully left Africa to colonize the rest of the world about 65,000–70,000 YBP. The founder mtDNA of macrohaplogroup N harbored two mtDNA missense mutations, ND3 G10398A (A114T) and ATP6 G8701A (A59T), whereas the founder of macrohaplogroup M did not harbor major functional mutations (3, 15). Early M and N emigrants from Africa moved through Southeast Asia, ending in Australia (96, 97). N mtDNAs also moved north from Africa into the Middle East to generate submacrohaplogroup R and European-specific haplogroups H, J, T, U, Uk, and V (from R) and I, W, and X (from N). N and R gave rise to Asian haplogroups A+Y and B+F, respectively. M moved north out of Southeast Asia to colonize Asia, generating haplogroups C and D and multiple M haplogroups. Haplogroups A, B, C, D, and X subsequently migrated to the Americas. The mtDNA mutation rate is 2.2%–2.9% per million years (numbers within the figure denote YBP). Figure adapted with permission from MITOMAP (5).