Findings Impact Evolutionary Theory

Convergent evolution, the acquisition of the same biological trait in unrelated lineages, is one of the most compelling arguments for the existence of natural selection. Classic examples of convergent evolution include the independent development of wings in dinosaurs (birds) and mammals (bats), and the development of similar water-retaining characteristics in New World cacti and African succulent plants. According to recent findings by researchers at the University of Colorado Denver School of Medicine, there is now a comparable example at the molecular genetic level.

Results from a current CU Denver School of Medicine study, Evidence for an Ancient Adaptive Episode of Convergent Molecular Evolution, published the week of April 27 in the Proceedings of the National Academy of Science Early Editions show widespread convergent molecular evolution across key parts of mitochondrial proteins from snakes and a distantly related group of lizards, the agamids, despite millions of years of evolutionary divergence between these groups. Furthermore, the study shows that such convergence can greatly disrupt the ability to understand how species are related to one another.

“I was stunned when I first saw these results,” said David Pollock, PhD, associate professor of biochemistry and molecular genetics at CU Denver, and corresponding author of the study. “It is highly unusual to find cases of convergent evolution in proteins, and even then there are usually only one or a few amino acids involved. The scale and scope of this event, involving many key functional positions and multiple proteins, has never been seen before. These results will have a big impact on the use of evolutionary inference in biomedical research.”

Jason de Koning, PhD, postdoctoral fellow at CU Denver and a primary author on the paper further explains: “Although it is well known that protein functions are modified during evolution, there are usually many ways such modifications can be achieved. Common adaptive pressures aren’t thought to necessarily lead to the same sequence changes.”

Given findings last year by these CU Denver researchers that snake mitochondrial genes have been radically evolutionarily redesigned, these new results suggest that drastic changes in core metabolic proteins may be more common in nature than scientists have thought. “Snakes are a sort of evolutionary crucible,” said Pollock. “This system can be used to understand not just how these proteins happen to function, but, in an evolutionary sense, why they function the way they do.”

“There are really two take home messages from this example,” said Todd Castoe, PhD, postdoctoral fellow at CU Denver and also a primary author on the paper. “The first is that molecular convergence can happen at a tremendous and previously unexpected scale in nature, which is exciting and potentially illuminating for understanding how proteins function and evolve. The second, a somewhat terrifying aspect to this research, is that it shows that even minor amounts of molecular convergence can mislead inferences of relationships among species or genes.” These inferences, called phylogenies, are an important cornerstone of modern research.

Added de Koning: “Phylogenies are used for everything from interpreting the human genome to reconstructing relationships among pathogens. We now know we will need to develop phylogenetic methods that are more robust to convergent changes caused by adaptation.”

“This work is the first compelling example that convergent adaptive evolution can influence the structure of a phylogenetic tree,” said Irene Eckstrand, PhD, who oversees evolution grants at the National Institutes of Health’s National Institute of General Medical Sciences, which partially supported the work. “It has changed our understanding of the relationships between organisms and will encourage other scientists to search for, and probably find, more evidence of this type of molecular evolution.”

The researchers plan to work with physiologists to better understand the common physiological pressures that might have led to these convergent molecular changes, and to search for more examples of protein convergence.

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