Mitochondrial-nuclear interactions: compensatory evolution or variable functional constraint among vertebrate oxidative phosphorylation genes?

Genome Biol Evol. 2013;5(10):1781-91. doi: 10.1093/gbe/evt129.


Oxidative phosphorylation (OXPHOS), the major energy-producing pathway in aerobic organisms, includes protein subunits encoded by both mitochondrial (mt) and nuclear (nu) genomes. How these independent genomes have coevolved is a long-standing question in evolutionary biology. Although mt genes evolve faster than most nu genes, maintenance of OXPHOS structural stability and functional efficiency may involve correlated evolution of mt and nu OXPHOS genes. The nu OXPHOS genes might be predicted to exhibit accelerated evolutionary rates to accommodate the elevated substitution rates of mt OXPHOS subunits with which they interact. Evolutionary rates of nu OXPHOS genes should, therefore, be higher than that of nu genes that are not involved in OXPHOS (nu non-OXPHOS). We tested the compensatory evolution hypothesis by comparing the evolutionary rates (synonymous substitution rate dS and nonsynonymous substitution rate dN) among 13 mt OXPHOS genes, 60 nu OXPHOS genes, and 77 nu non-OXPHOS genes in vertebrates (7 fish and 40 mammal species). The results from a combined analysis of all OXPHOS subunits fit the predictions of the hypothesis. However, results from two OXPHOS complexes did not fit this pattern when analyzed separately. We found that the d(N) of nu OXPHOS genes for "core" subunits (those involved in the major catalytic activity) was lower than that of "noncore" subunits, whereas there was no significant difference in d(N) between genes for nu non-OXPHOS and core subunits. This latter finding suggests that compensatory changes play a minor role in the evolution of OXPHOS genes and that the observed accelerated nu substitution rates are due largely to reduced functional constraint on noncore subunits.

Keywords: cytonuclear coevolution; dN; dS; evolutionary rates; nonsynonymous substitution; oxidative phosphorylation; synonymous substitution.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Catalytic Domain / genetics
  • Cell Nucleus / genetics*
  • Energy Metabolism / genetics*
  • Evolution, Molecular
  • Mitochondria / genetics*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Oxidative Phosphorylation*
  • Vertebrates / genetics


  • Mitochondrial Proteins