Protein-protein interfaces from cytochrome c oxidase I evolve faster than nonbinding surfaces, yet negative selection is the driving force.
Bottom Line: 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.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.
Affiliation: Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Spain email@example.com.Show MeSH
Mentions: As it can be observed in figure 3, among all exposed residues, those involved in interactions between different mtDNA-encoded chains were the most constrained, showing both the lowest ω and ΣdN values, regardless of the mtDNA-encoded subunit being considered. This observation indicates a much stronger purifying selection among Mt–mt Contact residues than among Mt–nu Contact amino acids. To substantiate this conclusion, we next assessed whether this differential behavior of the two subsets of contact residues had a broad phylogenetic distribution and was present in most mammalian lineages. To this end, we used the reconstructed tree to apportion the COX I nonsynonymous substitutions for the two categories of contact sites. Figure 8 shows the distribution of the statistic dNMt–nu − dNMt–mt among the phylogenetic tree branches, which was clearly biased toward positive values. Overall, these results suggest that those mtDNA-encoded residues in contact with mtDNA-encoded residues from a different chain are subjected to stronger constraints than those involved in interactions with nDNA-encoded subunits. In addition, this behavior seems to have a broad phylogenetic distribution and is valid for most mammalian lineages. To the best of our knowledge, this is the first quantitative study supporting such a conclusion.Fig. 8.—
Affiliation: Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Spain firstname.lastname@example.org.