Monday, January 19, 2015

Different selection forces at work on coral snake and rattlesnake venoms

Eastern Diamondback Rattlesnake
If you're one of the unfortunate few to be bitten by a venomous snake, having access to effective antivenom to combat the swelling, pain and tissue damage to these bites is critical.
But new research by a team of biologists at Florida State University has revealed that creating antivenom is a bit tricky.

That's because the type of venom a snake produces can change according to where it lives.

Mark Marges, a Florida State doctoral student in Professor Darin Rokyta's laboratory, led a research study that examined the venom of 65 eastern diamondback rattlesnakes and 49 eastern coral snakes from all over the state of Florida to determine whether snake venoms varied by geography.

The venom from an eastern diamondback rattlesnake in the Florida panhandle is very different than the venom from a rattlesnake 500 miles south in the Everglades, and this has huge implications for snakebite treatment.

"So if you use just southern venoms when making the antivenom, it would be ineffective against some of the more common toxins found in northern diamondback rattlesnakes," said Florida State University doctoral student Mark Margres.

In the rattlesnakes, they found significant variation linked to geography. But, in the coral snakes, they found the venom to be identical no matter where the snakes were found.

"This can tell us a bit of the history and evolutionary patterns of the snakes," said Kenny Wray, a post-doctoral research associate in Rokyta's lab. "This suggests that the coral snakes may be recent invaders to the region and haven't had time to evolve different venoms in different areas."

This information also will help with the development of coral snake antivenom, because scientists now know there is uniformity in coral snake venom. According to a 2012 estimate by the Center for Disease Control, 7,000 to 8,000 people in the United States are bitten by venomous snakes every year.

Not only are there medical implications, this information is also important for conservation purposes.

The eastern diamondback rattlesnake is being considered for federal protection under the Endangered Species Act. But, if the snakes are removed from one geographic area, they will be irrevocably deleted from the ecosystem altogether.

"If we lose some of these populations, we lose a whole venom type," Rokyta said. "That really changes conservation."

Venom from an eastern diamondback rattlesnake in the Everglades is distinct from the cocktail of toxins delivered by the same species in the Florida panhandle area, some 500 miles away. But no matter where you go in the Southeastern United States, the venom of the eastern coral snake is always the same.

Each venomous snake species produces a unique venom, a mixture of around 50-200 toxic proteins and protein fragments that co-evolve with the typical prey of the snake, such as the smaller reptiles eaten by the eastern coral snake or the rodents preferred by rattlesnakes. In this cycle of evolutionary attack and counterattack, any genetic variants that enhance venom resistance tend to spread through the prey population, prompting tweaks to the snake venom recipe that restore its effectiveness.

The result should be distinctive local co-adaptations between predator and prey, as well as considerable regional diversity in the types and amounts of the different venom proteins. But when Darin Rokyta (Florida State University) and his colleagues collected and profiled venom from eastern coral snakes at many sites within Florida, they found no variation at all. The mix of proteins in coral snake venom from one part of the state was indistinguishable from that collected anywhere else. In contrast, eastern diamondbacks, which live in the same parts of the country as the coral snakes, produce venom with different ratios of toxic proteins in nearly every sub-population across their range. For example, two venom components, including one known to cause paralysis in prey, are found at high levels in the northernmost populations, and were completely absent in the snakes from Caladesi Island, near Tampa.

"We were shocked," Rokyta said. "This is the first time anyone has looked at venom variation at this scale, and everybody has assumed that the co-evolutionary arms race would cause local populations to diverge quickly."

Rokyta says there could be several explanations for the lack of variation in eastern coral snake venom. For example, a small population of the species might have recently expanded and taken over the entire range, displacing other populations and reducing genetic diversity. Or it could reflect a difference in co-evolutionary dynamics between the species and its typically reptilian prey, compared to the small mammals preferred by rattlesnakes. The team is now using genetic clues to the population histories of each species to investigate possible explanations.

The results of the study will be helpful to researchers developing eastern coral snake antivenom. Making an antivenom requires samples of venom, but if the mix varies substantially from place to place, this will affect the drug's effectiveness and reliability. For this species, sampling from many populations should not be necessary. "This tells us it doesn't matter where we catch these relatively elusive snakes; we can stick to using those locations where they're easy to find," Rokyta said.

The variation between eastern diamondback populations could provide crucial information to authorities managing the conservation of this species, which is in decline and under consideration for listing as threatened under the Endangered Species Act. Eastern diamondback rattlesnake declines are thought to have been caused by habitat loss compounded by hunting and persecution by humans. The data from this study can be used for population management, to ensure the full range of venom subtypes are conserved for the long-term viability of the species.

"The received wisdom was that venoms are rapidly-evolving, but now we know that's not necessarily the case." said Mark Johnston, Editor-in-Chief of GENETICS. "Clearly, venom evolution in these two snake species has been shaped by different forces. The next challenge is to understand why."

Margres MJ, McGivern JJ, Seavy M, Wray KP, Facente J, Rokyta DR. 2014. Contrasting Modes and Tempos of Venom Expression Evolution in Two Snake Species. Genetics, 2014; DOI: 10.1534/genetics.114.172437

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