Adaptive Evolution of a Blood-Clotting Gene in Venom-Resistant Opossums

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Adaptive Evolution of a Blood-Clotting Gene in Venom-Resistant Opossums

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Action of snake venomHemolytic snake venoms—such as those found in rattlesnakes, moccasins, and lanceheads— are complex cocktails of proteases, phospholipases, and phospho-diesterases. One protein found in the venom of lancehead vipers (genus Bothrops) is botrocetin, which causes aggregation of blood platelets wherever von Willebrand Factor (vWF)and Factor VIII are present in the bloodstream (1).The blood plasma protein vWF and Factor VIII circulate freely in the blood vessel lumen during ordinary (laminar) flow. During normal blood clotting, turbulent blood flow—such as when a blood vessel ruptures—induces vWF to disengage from Factor VIII and complex with glycoprotein Ibαand collagen. This complex, by a series of reactions, aggregates platelets and fibrin to form blood clots (2). Thus, by binding vWF, botrocetin promotes inappropriate systemic clotting, reducing the ability of vWF to respond to ruptures caused by proteolytic venom proteins and promoting hemorrhage. Resistance in opossumsSeveral species of opossums in both North and South America are known to be resistant to lancehead venom—in fact, large opossums will even eat poisonous snakes (Figure 1). The mechanism by which they withstand snakebite is not known; our aim was to assess the possibility that mutations on the vWF gene may play a role in resistance.HyothesisBy calculating the rate of synonymous substitutions dSin the gene and the rate of non-synonymous substitutions dN(i.e., mutations that change the amino acid sequence of the resulting protein), we hope to detect posititve selective pressure. The ratio ω = dN/dS is a key statistic: if ω < 1, purifying selection is acting on this gene (i.e., mutations are purged); if ω = 1, no selection can be inferred; if ω> 1, positive, directional selection is acting on this gene. Our expectation is to find greater rates of substitution in the group of opossums highlighted in red in the phylogeny at right, because these are the species known to be resistant to snake venom.


Additional contributor: Sharon Jansa (faculty mentor).

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We are grateful for the support of the NSF North Star STEM Alliance in the conduct of this research.

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Sosa, Tim. (2010). Adaptive Evolution of a Blood-Clotting Gene in Venom-Resistant Opossums. Retrieved from the University Digital Conservancy,

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