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The <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>obzhansky\u2013<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>uller (<jats:styled-content style=\"fixed-case\">DM<\/jats:styled-content>) model nicely accounts for the evolution of such incompatibilities. Although <jats:styled-content style=\"fixed-case\">DM<\/jats:styled-content> incompatibilities were originally conceived as resulting of interactions between nuclear genes, recent studies have documented cases where incompatibilities have arisen between nuclear and mitochondrial genomes (mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>). Although mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> comprises only a tiny component (typically \u226a0.01%) of an organism's genetic material, several features of mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> may lead to a disproportionate contribution to the evolution of hybrid incompatibilities: (i) essentially all functions of mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> require interaction with nuclear gene products. All mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010encoded proteins are components of the oxidative phosphorylation (<jats:styled-content style=\"fixed-case\">OXPHOS<\/jats:styled-content>) system and all mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010encoded <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s are part of the mitochondrial protein synthetic machinery; both processes require interaction with nuclear\u2010encoded proteins for function. (ii) Transcription and replication of mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> also involve mitonuclear interactions as nuclear\u2010encoded proteins must bind to regulatory motifs in the mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> to initiate these processes. (iii) Although features of mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> vary amongst taxa, metazoan mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> is typically characterized by high nucleotide substitution rates, lack of recombination and reduced effective population sizes that collectively lead to increased chance fixation of mildly deleterious mutations. Combined, these features create an evolutionary dynamic where rapid mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> evolution favours compensatory nuclear gene evolution, ultimately leading to co\u2010adaptation of mitochondrial and nuclear genomes. When previously isolated lineages hybridize in nature or in the lab, intergenomic co\u2010adaptation is disrupted and hybrid breakdown is observed; the role of intergenomic co\u2010adaptation in hybrid breakdown and speciation will generally be most pronounced when rates of mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> evolution are high or when restricted gene flow results in significant population differentiation.<\/jats:p>","DOI":"10.1111\/mec.12006","type":"journal-article","created":{"date-parts":[[2012,9,21]],"date-time":"2012-09-21T10:27:33Z","timestamp":1348223253000},"page":"4942-4957","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":332,"title":["A disproportionate role for mt<scp>DNA<\/scp> in <scp>D<\/scp>obzhansky\u2013<scp>M<\/scp>uller incompatibilities?"],"prefix":"10.1111","volume":"21","author":[{"given":"Ronald S.","family":"Burton","sequence":"first","affiliation":[{"name":"Marine 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