Three-dimensional representation of relevant variable amino acids in mammalian cytochrome b. Illustrative representation of some of the amino acid variable sites (see Figure 10) located in relevant functional spots of the bovine CytB structure (pdb code: 1PPJ ). The prosthetic groups in CytB are represented in black, and the Qi and QP bound inhibitors in orange (ant: antimycin; stig: stigmatellin). Mutations in sites shown in red have been related to exercise intolerance in humans (see Table 1). Mutations in sites shown in pink are under strong positive selection according to the TreeSAAP analysis (over 5 positively selected properties). In site 277, the alanine present in the bovine structure is shown as ball and stick and the van der Waals surface for the arginine found in dugong is also depicted. MM: mitochondria matrix; IM: intermembrane space.