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Cytochrome c oxidase assembly in primates is sensitive to small evolutionary variations in amino acid sequence

  1. Author:
    Barrientos, A.
    Muller, S.
    Dey, R.
    Wienberg, J.
    Moraes, C. T.
  2. Author Address

    Univ Miami, Sch Med, Dept Neurol, 1501 NW 9th Ave, Miami, FL 33136 USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL 33136 USA. Univ Munich, Inst Anthropol & Humangenet, Munich, Germany. NCI, Lab Genom Divers, Frederick, MD USA. Univ Miami, Sch Med, Dept Cell Biol & Anat, Miami, FL 33136 USA.
    1. Year: 2000
  1. Journal: Molecular Biology and Evolution
    1. 17
    2. 10
    3. Pages: 1508-1519
  2. Type of Article: Article
  1. Abstract:

    Respiring mitochondria require many interactions between nuclear and mitochondrial genomes. Although mitochondrial DNA (mtDNA) from the gorilla and the chimpanzee are able to restore oxidative phosphorylation in a human cell, mtDNAs from more distant primate species are functionally incompatible with human nuclear genes. Using microcell-mediated chromosome and mitochondria transfer, we introduced and maintained a functional orangutan mtDNA in a human nuclear background. However, partial oxidative phosphorylation function was restored only in the presence of most orangutan chromosomes, suggesting that human oxidative phosphorylation-related nuclear-coded genes are not able to replace many orangutan ones. The respiratory capacity of these hybrids was decreased by 65%-80%, and cytochrome c oxidase (COX) activity was decreased by 85%-95%. The function of other respiratory complexes was not significantly altered. The translation of mtDNA-coded COX subunits was normal, but their steady-state levels were similar to 10% of normal ones. Nuclear-coded COX subunits were loosely associated with mitochondrial membranes, a characteristic of COX assembly-defective mutants. Our results suggest that many human nuclear-coded genes not only cannot replace the orangutan counterparts, but also exert a specific interference at the level of COX assembly. This cellular model underscores the precision of COX assembly in mammals and sheds light on the nature of nuclear-mtDNA coevolutionary constraints.

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