title: Evolution and disease converge in the mitochondrion.
abstract: Mitochondrial DNA (mtDNA) mutations are long known to cause diseases but also underlie tremendous population divergence in humans. It was assumed that the two types of mutations differ in one major trait: functionality. However, evidence from disease association studies, cell culture and animal models support the functionality of common mtDNA genetic variants, leading to the hypothesis that disease-causing mutations and mtDNA genetic variants share considerable common features. Here we provide evidence showing that the two types of mutations obey the rules of evolution, including random genetic drift and natural selection. This similarity does not only converge at the principle level; rather, disease-causing mutations could recapitulate the ancestral DNA sequence state. Thus, the very same mutations could either mark ancient evolutionary changes or cause disease.
authors.affiliation: Department of Life Sciences, National Institute of Biotechnology in the Negev (NIBN), Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. dmishmar@bgu.ac.il
authors.forename: D
authors.initials: D
authors.lastname: Mishmar
authors.forename: I
authors.initials: I
authors.lastname: Zhidkov
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics*; D019143:Evolution, Molecular; D040961:Genetic Drift; D014644:Genetic Variation; D054629:Genome, Mitochondrial; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D012641:Selection, Genetic
chemical_list: D004272:DNA, Mitochondrial