Mitochondrial DNA variation in human radiation and disease

Abstract

Environmental adaptation, predisposition to common diseases, and, potentially, speciation may all be linked through the adaptive potential of mitochondrial DNA (mtDNA) alterations of bioenergetics. This Perspective synthesizes evidence that human mtDNA variants may be adaptive or deleterious depending on environmental context and proposes that the accrual of mtDNA variation could contribute to animal speciation via adaptation to marginal environments.

Figure 1. Regional Radiation of Human mtDNAs from their Origin in Africa and Colonization of Eurasia and the Americas Implies that Environmental Selection Constrained Regional mtDNA Variation

All African mtDNAs are subsumed under macrohaplogroup L and coalesce to a single origin about 130,000–170,000 YBP. African haplogroup L0 is the most ancient mtDNA lineage found in the Koi-San peoples, L1 and L2 in Pygmy populations. The M and N mtDNA lineages emerged from Sub-Saharan African L3 in northeastern Africa, and only derivatives of M and N mtDNAs successfully left Africa, giving rise to macrohaplogroups M and N. N haplogroups radiated into European and Asian indigenous populations, while M haplogroups were confined to Asia. Haplogroups A, C, and D became enriched in northeastern Siberia and were positioned to migrate across the Bering Land Bridge 20,000 YBP to found Native Americans. Additional Eurasian migrations brought to the Americas haplogroups B and X. Finally, haplogroup B colonized the Pacific Islands. Figure reproduced from (MITOMAP, 2015).

Figure 2. Hypothetized Role of mtDNA Variation in Animal Environmental Adaptation and Speciation

This figure portrays the environmental space (niche) of successively evolving species (green, orange, and blue horizontal bands). The left-to-right expanse represents the range of ecological zones for each species, with the center (M) being the optimal environment and the two left and right vertical dashed lines (SD1 and SD2) representing increasingly marginal environments. Successive mtDNA mutations occurring over time are represented by branch points on black lines, with most of them being neutral. As a new species expands from its optimal niche into more marginal environments, occasional mtDNA mutations arise, which are physiologically beneficial in the suboptimal environment (blue circles at branch points). These lineages become enriched by adaptive selection with additional neutral and adaptive mutations accumulating, creating a haplogroup. The same environmental constraint can select for the same mutation on different mtDNA lineages. Occasionally, one mtDNA lineage located at the extreme edge of the species’ niche (left and right edges) permits a subpopulation to persist long enough for nDNA variants to arise that permit switching of food source (energy reservoir), leading to speciation (open circle crossing species boundaries). Previously adaptive mtDNA variants now become suboptimal in the new niche and revertants are selected, permitting energetic re-adaptation back to M.