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: We recalculated the interaction ratio for the Mt–nu Contact category, but now using the Exposed Noncontact as the reference set. In this way, we obtained a ratio of 1.18, which although much lower than 1.81 (the value obtained when no proper control was used), it is still over the unit. At this point, one may feel tempted to conclude that Mt–nu Contact residues evolve almost 1.2 times faster than noncontact residues, which would favor the optimizing hypothesis. However, when each individual chain was separately analyzed, we reached a different conclusion. For instance, when the same ΣdN values used to compute the interaction ratio were plotted for each subunit (fig. 3A), it becomes clear-cut that, with the exception of COX I, the Exposed Noncontact groups accumulate more nonsynonymous substitutions than their Mt–nu Contact counterparts. As Mt–nu Contact amino acids exhibit on average higher accessible surface areas than Exposed Noncontact residues (79.2 ± 43.6 vs. 56.2 ± 42.8 Å2, respectively), we can rule out the possibility that the former may be evolving slowly because they are more buried than Exposed Noncontact residues.Fig. 3.—
Affiliation: Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Spain firstname.lastname@example.org.