Ancestry and health: a mitochondrial DNA perspective

Abstract

This chapter explores the role of mitochondrial DNA (mtDNA) in human evolution and human health. The unique features of mtDNA, including maternal inheritance, high mutation rates, and heteroplasmy are fundamental to understanding both population diversity and disease manifestation. Leber's Hereditary Optic Neuropathy serves as a model disease to demonstrate how these unique features influence disease manifestation in addition to primary mtDNA mutations. The evolution of mtDNA haplogroups is traced from their African origins through global dispersal, revealing how selective pressures may have shaped variations in oxidative phosphorylation efficiency across populations. Growing evidence links mtDNA haplogroups to various diseases, from neurodegenerative disorders to metabolic conditions, though there are challenges in establishing and generalizing such associations, due to heteroplasmy, population genetic structure, and mitochondrial-nuclear genome interactions. Understanding these complex interactions is crucial for developing personalized approaches to mitochondrial disorders and interpreting the role of mtDNA variations in human health and disease.