Adaptive selection of mitochondrial complex I subunits during primate radiation

Area of Science:

• Evolutionary biology
• Molecular biology
• Genetics

Background:

• Mammalian oxidative phosphorylation (OXPHOS) complexes are assembled from nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) encoded subunits.
• Complex I, crucial for energy production, comprises 39 nDNA and 7 mtDNA subunits.
• mtDNA genes exhibit higher sequence variation and have shown evidence of positive selection compared to nDNA genes.

Purpose of the Study:

• To investigate whether positive selection has also influenced nDNA-encoded complex I genes.
• To explore potential co-evolution between nDNA and mtDNA subunits within complex I.

Main Methods:

• Analyzed DNA sequences of all nDNA and mtDNA complex I subunits across primates (orangutan, gorilla, chimpanzee, human) and other vertebrates.
• Utilized PAML and Z-test to assess amino acid substitution rates and detect positive selection.
• Compared amino acid changes in specific nDNA subunits with mtDNA subunits residing in the membrane domain.

Main Results:

• Three nDNA complex I genes (NDUFC2, NDUFA1, NDUFA4) showed significantly increased amino acid substitution rates, indicating adaptive selection during primate evolution.
• These selected nDNA subunits are located in the membrane domain, alongside mtDNA subunits.
• Amino acid changes in nDNA NDUFC2 correlated with changes in mtDNA ND5, suggesting functional interdependence.

Conclusions:

• Adaptive selection has influenced specific nDNA-encoded complex I genes.
• Evidence suggests co-evolution between nDNA and mtDNA subunits of complex I.
• These findings highlight the intricate evolutionary interplay maintaining mitochondrial function.