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Adaptive Evolution in Snake Proteins Could Give Insight into Human Metabolic Function and Physiology

According to researchers at the University of Colorado Denver School of Medicine, new understanding about snake proteins could lead to understanding how other animals including humans accomplish aerobic respiration, and also contribute new insight into protein function and evolution important for human health.

Snakes have been previously proposed as an ideal model system to study evolution, and results from a current UC Denver School of Medicine study published in Public Library of Science (PLoS) ONE journal on May 21, support that idea, showing that their use as a model system can extend to the molecular level.

Over the last ten years, scientists have shown that snakes have remarkable abilities to regulate heart and digestive system development. They endure among the most extreme shifts in aerobic metabolism known in vertebrates. This has made snakes an excellent model for studying organ development, as well as physiological and metabolic regulation. However, the reasons that snakes are so unique had not previously been identified at the molecular level.

In the NIH-grant-funded study, David Pollock, PhD, associate professor of biochemistry and molecular genetics at the UC Denver School of Medicine, and his colleagues provide evidence that the major evolutionary changes that have occurred in snakes, such as adaptations for their extreme physiology and metabolic demands, loss of limbs and the evolution of deadly venoms, have been accompanied by massive functional redesign of core metabolic proteins.

Prior to the advent of large sequence datasets, the scientific community generally expected that innovation and divergence at the morphological and physiological level would be easily explained at the molecular level. However, molecular explanations for physiological adaptations have been rare. The UC Denver researchers show that some proteins in snakes have endured a remarkable process of evolutionary redesign that may explain why snakes have such special metabolism and physiology. Amino acids that are normally highly conserved in these proteins have been altered, affecting key molecular functions. In addition to an accelerated burst of amino acid replacements, evidence for adaptation comes from exceptional levels of molecular co-evolution and convergence at the functional core of these proteins.

“The molecular evolutionary results are remarkable, and set a new precedence for extreme protein evolutionary adaptive redesign. This represents the most dramatic burst of protein evolution in an otherwise highly conserved protein that I know of,” said Dr. David Pollock.

By integrating analyses of molecular evolution with protein structural data, the authors show that critical functions of mitochondrial proteins have been fundamentally altered during the evolution of snakes.

“We believe that our results will provide a textbook case as the most clear and dramatic example of adaptive evolution in a core metabolic protein to date, as well as providing the implication that strong molecular and physiological adaptation can be linked,” said Pollock. “The manuscript represents an important milestone in molecular evolution and vertebrate adaptation, and opens up clear and well-justified directions for further research. Many proteins that lie at the functional core of aerobic metabolism are difficult to study and we still know surprisingly little about them, despite much scientific effort. Snake metabolic proteins can increase our understanding of how these proteins function because they seem to break many of the rules, but apparently still work, and possibly work even better.”

Todd Castoe, PhD, UC Denver School of Medicine, and a lead author on the paper, said: “Snakes are an invaluable resource for evolutionary biologists, structural biologists and biochemists who can use comparative genomics to generate hypotheses for how proteins function, and how these functions may be altered and redesigned. From what we have seen so far, snakes may be the single best model system for studying extreme adaptive evolution in vertebrates.”

The full text of the paper is available at

The School of Medicine faculty work to advance science and improve care as the physicians, educators and scientists at University of Colorado Hospital, The Children’s Hospital, Denver Health, National Jewish Medical and Research Center, and the Denver Veterans Affairs Medical Center. Degrees offered by the UC Denver School of Medicine include doctor of medicine, doctor of physical therapy, and masters of physician assistant studies. The School is part of the University of Colorado Denver, one of three universities in the University of Colorado system. For additional news and information, please visit the UC Denver newsroom online.

Caitlin Jenney | newswise
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Further reports about: Adaptation Core Evolution Protein metabolic physiological vertebrate

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