How Snakes Became Resistant To Their Toxic Newt Prey

A snake eating a newt carrying toxins. Richard Greene

Some snakes are incredibly resistant to toxins found in the newts they eat. This adaptation required changes in several genes over millions and millions of years, according to findings published in Current Biology last week. And these changes arose in reptiles long before snakes even evolved.

Common garter snakes (Thamnophis sirtalis) and several other modern snake species are able to eat salamanders like the rough-skinned newt (Taricha granulosa) thanks to their resistance to tetrodotoxin, or TTX. This toxin works by blocking sodium channels, which allow the movement of important ions through various membranes. In non-resistant victims (including people), the toxin can cause numbness and paralysis.


The extreme resistance to TTX seen in snakes requires changes in multiple genes. But novel adaptations have to originate and function within a genome that’s already established. So did these changes arise all at once or were they accrued over evolutionary time? To reconstruct the history of TTX-resistance genes in snakes, a team led by Virginia Tech’s Joel McGlothlin sequenced genes from 78 snake species. They focused on genes that code for amino acids in three different sodium channels found in the snakes' nerves and muscles.

The team found that the ability to withstand the newt toxin – and resist the numbing and paralyzing effects – evolved in a “stepwise” fashion, in which evolutionary change in one gene leads to change in another. In this case, resistant nerves always evolved before resistant muscle. Some snakes built up more resistance than others, but the changes always occurred in that same order.

Ancestors of garter snakes, for instance, gained resistant nerves some 40 million years ago. "Garter snakes and newts are locked in a coevolutionary arms race whereas the newts become more toxic, the snakes become more resistant," McGlothlin explained in a statement. "However, without the leg-up provided by those resistant nerves, snakes wouldn't have been able to withstand enough toxin to get this whole process started." 

Furthermore, TTX-resistance in sensory neurons evolved in reptiles before the origin of snakes. The first change that helped confer resistance arose in lizards some 170 million years ago, and it was present in the common ancestor all snakes. A second change occurred beginning 38 million years ago in four snake lineages, and extreme TTX-resistance evolved at least five times within the last 12 million years via changes in sodium channels – but only in lineages that had evolved the previous two changes. 


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