Evolution of Mitochondrial Power in Vertebrate Metazoans

Background: Basal metabolic rate (BMR) has a very strong body-mass (M) dependence in an individual animal group, and BMR per unit mass (msBMR) converges on a markedly narrow range even across major taxonomic groups. However, it is here a basic question in metazoan biology how much BMR per unit mitochondrion (mtBMR) changes, and then whether mtBMR can be related to the original molecular mechanism of action of mt-encoded membrane proteins (MMPs) playing a central role in cellular energy production. Methodology/Principal Findings: Analyzing variations of amino-acid compositions of MMPs across 13 metazoan animal groups, incorporating 2022 sequences, we found a strong inverse correlation between Ser/Thr composition (STC) and hydrophobicity (HYD). A majority of animal groups showed an evolutionary pathway of a gradual increase in HYD and decrease in STC, whereas only the deuterostome lineage revealed a rapid decrease in HYD and increase in STC. The strongest correlations appeared in 5 large subunits (ND4, ND5, ND2, CO1, and CO3) undergoing dynamic conformational changes for the proton-pumping function. The pathway of the majority groups is well understood as reflecting natural selection to reduce mtBMR, since simply raising HYD in MMPs (surrounded by the lipid bilayer) weakens their mobility and strengthens their stability. On the other hand, the marked decrease in HYD of the deuterostome elevates mtBMR, but is accompanied with their instability heightening a turnover rate of mitochondria and then cells. Interestingly, cooperative networks of interhelical hydrogen-bonds between motifs involving Ser and Thr residues can enhance MMP stability. Conclusion/Significance: This stability enhancement lowers turnover rates of mitochondria/cells and may prolong even longevity, and was indeed founded by strong positive correlations of STC with both mtBMR and longevity. The lowest HYD and highest STC in Aves and Mammals are congruent with their very high mtBMR and long longevity.