title: Adaptive evolution and functional redesign of core metabolic proteins in snakes.
abstract: BACKGROUND
  Adaptive evolutionary episodes in core metabolic proteins are uncommon, and are even more rarely linked to major macroevolutionary shifts.
  
  
  RESULTS
  We conducted extensive molecular evolutionary analyses on snake mitochondrial proteins and discovered multiple lines of evidence suggesting that the proteins at the core of aerobic metabolism in snakes have undergone remarkably large episodic bursts of adaptive change. We show that snake mitochondrial proteins experienced unprecedented levels of positive selection, coevolution, convergence, and reversion at functionally critical residues. We examined Cytochrome C oxidase subunit I (COI) in detail, and show that it experienced extensive modification of normally conserved residues involved in proton transport and delivery of electrons and oxygen. Thus, adaptive changes likely altered the flow of protons and other aspects of function in CO, thereby influencing fundamental characteristics of aerobic metabolism. We refer to these processes as "evolutionary redesign" because of the magnitude of the episodic bursts and the degree to which they affected core functional residues.
  
  
  CONCLUSIONS
  The evolutionary redesign of snake COI coincided with adaptive bursts in other mitochondrial proteins and substantial changes in mitochondrial genome structure. It also generally coincided with or preceded major shifts in ecological niche and the evolution of extensive physiological adaptations related to lung reduction, large prey consumption, and venom evolution. The parallel timing of these major evolutionary events suggests that evolutionary redesign of metabolic and mitochondrial function may be related to, or underlie, the extreme changes in physiological and metabolic efficiency, flexibility, and innovation observed in snake evolution.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Castoe
authors.forename: Zhi J
authors.initials: ZJ
authors.lastname: Jiang
authors.forename: Wanjun
authors.initials: W
authors.lastname: Gu
authors.forename: Zhengyuan O
authors.initials: ZO
authors.lastname: Wang
authors.forename: David D
authors.initials: DD
authors.lastname: Pollock
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D003576:Electron Transport Complex IV / Q000235:genetics; D019143:Evolution, Molecular; D011506:Proteins / Q000378:metabolism*; D012911:Snakes / Q000235:genetics / Q000502:physiology*
chemical_list: D011506:Proteins; D003576:Electron Transport Complex IV