title: Protein-protein interfaces from cytochrome c oxidase I evolve faster than nonbinding surfaces, yet negative selection is the driving force.
abstract: Respiratory complexes are encoded by two genomes (mitochondrial DNA [mtDNA] and nuclear DNA [nDNA]). Although the importance of intergenomic coadaptation is acknowledged, the forces and constraints shaping such coevolution are largely unknown. Previous works using cytochrome c oxidase (COX) as a model enzyme have led to the so-called "optimizing interaction" hypothesis. According to this view, mtDNA-encoded residues close to nDNA-encoded residues evolve faster than the rest of positions, favoring the optimization of protein-protein interfaces. Herein, using evolutionary data in combination with structural information of COX, we show that failing to discern the effects of interaction from other structural and functional effects can lead to deceptive conclusions such as the "optimizing hypothesis." Once spurious factors have been accounted for, data analysis shows that mtDNA-encoded residues engaged in contacts are, in general, more constrained than their noncontact counterparts. Nevertheless, noncontact residues from the surface of COX I subunit are a remarkable exception, being subjected to an exceptionally high purifying selection that may be related to the maintenance of a suitable heme environment. We also report that mtDNA-encoded residues involved in contacts with other mtDNA-encoded subunits are more constrained than mtDNA-encoded residues interacting with nDNA-encoded polypeptides. This differential behavior cannot be explained on the basis of predicted thermodynamic stability, as interactions between mtDNA-encoded subunits contribute more weakly to the complex stability than those interactions between subunits encoded by different genomes. Therefore, the higher conservation observed among mtDNA-encoded residues involved in intragenome interactions is likely due to factors other than structural stability.
authors.affiliation: Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Spain caledo@uma.es.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Aledo
authors.affiliation: Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Spain.
authors.forename: Héctor
authors.initials: H
authors.lastname: Valverde
authors.affiliation: Departamento de Estadística e Investigación Operativa, Facultad de Ciencias, Universidad de Málaga, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ruíz-Camacho
authors.affiliation: Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Spain.
authors.forename: Ian
authors.initials: I
authors.lastname: Morilla
authors.affiliation: Departamento de Estadística e Investigación Operativa, Facultad de Ciencias, Universidad de Málaga, Spain.
authors.forename: Francisco Demetrio
authors.initials: FD
authors.lastname: López
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012641:Selection, Genetic
chemical_list: D004272:DNA, Mitochondrial; D021122:Protein Subunits; D003576:Electron Transport Complex IV
keywords: COX; cytonuclear coevolution; evolutionary rates; mitochondria; oxidative phosphorylation; protein evolution