Getting Out of the Water: Did Aerobic Capacity Give Vertebrates a Leg Up?
The sprint of a cheetah and the lumberings of a tortoise are powered by the same source: a set of cellular machinery, embedded in the mitochondria, shared by all eukaryotic life. Differences between the swift, the slow, and an animal's length of life may lie in the motility of that machinery itself, a new study suggests.The power and endurance of a vertebrate's respiratory engine is closely linked to the hydrophobicity and stability of their mitochondrial membrane proteins, report a team of researchers in the current issue of Genome Biology and Evolution (Kitazoe et al. 2011). The team, composed of researchers from Japan and the United Kingdom, conducted a sweeping analysis of mitochondrial membrane proteins in vertebrates.“The critical interpretation of this relationship is that the more energy you require for your life, the less likely you are to have hydrophobic membrane proteins,” said Nick Lane, a biochemist at University College London and paper coauthor. “This relationship was quite unexpected.”Animals with relatively hydrophilic membrane proteins tend to have lengthy life spans, they find, suggesting that a trend away from hydrophobicity was key to the evolution of long-lived, active, land-dwelling animals like birds and primates.The higher aerobic capacity of these animals requires their membrane proteins to be more mobile—less embedded into the membrane lipid bilayer—the authors suggest, so that they have the ability to assemble into mitochondrial supercomplexes at high metabolic rates to supercharge energy production.To compensate for the increased protein mobility and aerobic capacity, the mitochondrial genome has possibly selected for serine/threonine complexes (STC), stability-boosting amino acids, a trend clearly shown in authors' results. The additional STC, they predict, stabilizes the supercomplexes with enhanced, short-range, hydrogen-bonding potential.To paint an analogy, one can imagine the protein complexes responsible for cellular respiration as boats floating in a sea of phospholipids. Highly hydrophobic proteins would be like a tugboat: deeply sunk into the sea and difficult to maneuver. Membrane proteins with low hydrophobicity would be more like a hydrofoil, skimming the water's surface. Assembling these into respiratory supercomplexes would be like linking together sets of ships into a cavalcade for advanced nautical operations.The trend toward mobility in mitochondrial membrane proteins was apparently important for vertebrates to colonize land, said Lane, as the correlation is very strong. Vertebrates may not have been successful on land without it, “or perhaps we would have all been slug-like creatures.”Lane still encourages a cautious interpretation of the findings, however, as the study represents early work: “This is quite an intriguing paper, but many of the answers about what it really means are not in place yet.”Yasuhiro Kitazoe, primary author and bioinformatician at the Kochi Medical School in Japan, has already begun to look at this question. He expects to see the correlation hold beyond vertebrates.“The great diversification of Metazoa animals has been realized by a quite powerful energy production of mitochondria,” wrote Kitazoe in an email. “So it is interesting to clarify in more detail a mechanism of this energy production caused by the mitochondrial membrane proteins.”Neil Blackstone, biology professor at Northern Illinois University, believes the paper will attract a lot of attention while urging some caution in its reception.“I think they're on to something,” said Blackstone. “I don't think anyone has found these patterns before, and they are very striking patterns. It is a bold and integrative approach, maybe a little bit too bold in some ways.”The evolutionary analysis, said Blackstone, is not very refined. Fish, for example, are placed as one phylogenetic group, although most evolutionary biologists would consider them several separate groups. Biophysicists might take exception at their use of the term “stability” for membrane proteins, because, from another point of view, more hydrophobic membrane proteins—sunk more deeply into the membrane bilayer—could be considered more “stable.”“Still, they've uncovered fascinating patterns in the data,” Blackstone said.Many other researchers, such as physiologists and functional biologists, Blackstone expects, will want to further explore the work.“Often the best science gets done when someone presents a really interesting synthesis, opening questions for other experts to follow up on.”