Evolutionary biology:  Channels of resistance
Rory Howlett
Nature 434, 716 (7 April 2005) | doi: 10.1038/434716a

Two studies reported in this issue provide striking examples of how biologists are getting to grips with adaptive diversification at the molecular level. They deal with two very different animals — one a marine invertebrate and the other a terrestrial vertebrate.
The softshell clam (Mya arenaria) occurs around the Atlantic coast of North America. The clams can become contaminated with saxitoxin, the cause of paralytic shellfish poisoning in humans and economic losses to the shellfish industry. The toxin is produced by 'red tide' algae and finds its way into the clams when the algae are ingested. V. Monica Bricelj et al. (Nature 434, 763-767; 2005) show that clams from areas subject to recurrent red tides are relatively resistant to the toxin and tend to accumulate it in their tissues. But clams from unaffected areas have low resistance when exposed to the toxin in the laboratory. These differences were mirrored by the sensitivity of isolated clam nerve-trunks exposed to the toxin in vitro.
To investigate the underlying molecular mechanism, Bricelj et al. sequenced the genomic region encoding a putative voltage-gated sodium channel. Such channels sit in cell membranes and regulate ion flow. The authors found a single mutation that correlated with resistance to the toxin, and that results in replacement of a glutamic acid by aspartic acid at a site previously implicated in the binding of saxitoxin. When introduced into a channel from rat brain, this mutation did not affect ion conductance. But the sensitivity of the channel to saxitoxin was greatly reduced owing to a large decrease in the binding affinity of the toxin at the channel pore.
Saxitoxin produced by red-tide algae probably acts as a potent selective agent on the clams, leading to genetic adaptation, the target of selection being genetic variation at a single site in an ion channel.
E. D. BRODIE
But this phenomenon is not unique to clams. Saxitoxin is related to another nerve poison called tetrodotoxin (TTX). In some populations of the newt Taricha granulosa, individuals accumulate large amounts of TTX in their skin as a defence against garter snakes (Thamnophis sirtalis; pictured). As a result, the snakes that prey on toxic newts have evolved high levels of resistance to the toxin. Shana L. Geffeney et al. (Nature 434, 759-763; 2005) show that variation in the level of resistance of garter snakes co-evolving with their newt prey can be traced to molecular changes that affect the binding of TTX to — you guessed it — a sodium channel.
So similar mechanisms underlie the adaptation of both softshell clams and garter snakes to regular neurotoxin exposure. Evolution is baroque in its many aspects, but is sometimes more predictable than we imagine.