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Snake venom evolved in fits and spurts

Snake venom, including from the Okinawa Habu (Protobothrops flaviviridis), evolved in punctuated, rapid bursts over the last 60 million years. Image credit: Alexander Mikheyev.

Snake venom, including from this habu, evolved in pulsed bursts over the last 60 million years. Image credit: Alexander Mikheyev.

The cocktail of toxins in snake venom experienced constant change with pulses of rapid evolution over the last 60 million years, according to a recent study in the Proceedings of the Royal Society B. Venom, the researchers report, has changed in some snake lineages over timespans as brief as a million years—though whether these changes helped spur diversification is still an open question.

Coauthors Alexander Mikheyev and Agneesh Barua began the study with a phylogeny of 52 venomous snake lineages and the known modern RNA expression levels of toxins in each of the snake’s venoms. The authors then fit a series of evolutionary models to the data, explains Mikheyev, an evolutionary biologist at Australian National University in Canberra. In order to best explain the venom’s modern composition, the authors tested a variety of alternative scenarios about how it had evolved. One model, for instance, assumed an ancestral venom arose in a snake common ancestor and evolved randomly through all 52 lineages. But the model that best fit the data assumed that the evolution of gene expression proceeded constantly, with pulsed periods of rapid change in toxin expression levels.

The results fit expectations, says Barua, a doctoral candidate in ecology and evolution at the Okinawa Institute of Science and Technology Graduate University in Japan. After all, since snakes primarily use their venom to capture food, they’re in a constant evolutionary arms race with their prey’s immune systems. Rapid evolutionary jumps could open up new avenues for prey capture. “For as long as people have studied snake venom, everyone had this intuition that [it] evolves really fast,” he says. The new study is among the first to back up that assumption with quantitative evidence

Rapid evolutionary jumps have often been associated with the rise of new species in the field of evolutionary biology, Mikheyev says. New traits may change the ecology or behavior of a species, provide access to resources, and sometimes can cause reproductive isolation of populations. Evolutionary biologist James Stroud at Washington University in St. Louis, MO points to the evolution of flight in bats and birds, which may have opened access to new prey and led to species diversification, he says. Similarly, “investigating whether venoms played a role in the diversification of snakes is an incredibly exciting idea in evolutionary biology,” Stroud says.

But in the case of snakes, there’s little evidence that venom changes affected mate selection or otherwise influenced reproduction. Indeed, the study’s findings seem to suggest that the diversification of venoms is not responsible for the diversity of snakes. When the authors checked for patterns indicating that periods of rapid venom diversification tightly correlated with periods of snake diversification, they didn’t find evidence for those trends. Ideally, future studies would compare the phylogeny with an evolutionary model of venom evolution, Barua says. But for that, he adds, researchers would need more data from more snakes

Additional analyses—those able to pick up more subtle differences rather than broad-scale patterns—could test for a more subtle link between trait evolution and speciation throughout the snake tree, notes macroevolutionary biologist Luke Harmon at the University of Idaho in Moscow, ID. Still, Harmon agrees with the authors in principle that traits like venom could evolve without necessarily causing reproductive isolation or speciation.

Harmon sees the recent paper as a rich resource of hypotheses for future studies. For example, in some cases, the expression of two or three toxin genes changed at once. “I’d go look at those snakes and ask, have they changed their diet, moved to a different habitat?” he says, alluding to possible future work. “We don’t know that much about what drives evolution across venomous and poisonous organisms in general, and this is a trait where we actually know the genetic basis of the gene.” Knowing which genes encode which toxins means that in future studies, researchers could use evolutionary models, he says, to look across the diets or environmental conditions of many snake species to test which factors influenced the evolution of venom gene expression.

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