Question

The rough-skinned newt, Taricha granulosa, is a common prey for garter snakes, Thamnophis sirtalis. Several populations of newts in Oregon have individuals that can accumulate a nerve poison, tetrodotoxin (TTX) in their skin. Garter snakes that prey on newts become poisoned if they eat a TTXproducing newt. TTX is poisonous because it binds to the voltage-gated Na+ channel protein that is found on the membrane of nerve cells and blocks electrical signaling in nerve and muscle cells; TTX poisoning results in paralysis and can be fatal. However, resistance to TTX has evolved in some garter snake populations. The TTX-resistant phenotype in snakes is associated with mutations in the voltage-gated sodium channel (NaV) gene. One of these mutations, D1684N, results in a version of the sodium channel (NaV) protein that is still functional, but unable to bind to the TTX molecule. Garter snakes with genotype D/D are sensitive to TTX; garter snakes with genotype D/N or N/N are resistant to TTX but crawl more slowly than snakes with genotype D/D.

a) Refer to the wild-type allele of NaV as the D allele, and to the mutant allele as the N allele. Garter snakes with genotype D/D are sensitive to TTX; garter snakes with genotype D/N or N/N are resistant to TTX. Is the D allele dominant or recessive? Clearly state your answer, and briefly explain your reasoning.

b) Briefly explain why a garter snake with genotype D/N is resistant to tetrodotoxin.

c) Assume that the ancestors of garter snakes were all had genotype D/D. Briefly explain how (by what mechanism and during what process) and why (for what reason) the D1684N mutation most likely first appeared in a garter snake.

d)You would expect the N allele in garter snakes to be under positive selection:  only in locations where TTX-producing newts are present  only in locations where TTX-producing newts are absent  in all locations?

Answer 1

A.

D/D genotype is sensitive to TTX poison while D/N and N/N contribute in TTX resistance in garter snakes. Garter snakes are affected by TTX poison only when they have two copies of this lethal allele(D). This means, in the presence of two mutated alleles i.e. DD, the voltage gated NA+ channel becomes completely non-functional and lethal. While in other genotypes (D/N and N/N), mutated N allele functions as dominant allele and suppresses the activity of D allele.

B.

In a heterozygous condition i.e. D/N, the organism has atleast one TTX resistant allele which is able to block TTX toxin. This is because mutated allele N is dominant over ancestral allele D and thus, able to repress D allele.

C.

TTX resistance in garter snakes appeared to arise as a reult of evolution. It has been observed that mutations in several voltage-gated sodium (NaV) channels led to the TTX resistance. Of all, three important NaV paralogs i.e. NaV1.4, NaV1.6 and NaV1.7 play significant role in this phenomenon. NaV1.4 serves as skeletal muscle channel. NaV1.6 functions in myelinated sheath of nerve fibres while NaV1.7 is known to express in smooth muscle fibres. Mutations in these channels caused amino acid substitution at various location due to which, these organisms have TTX resistance. Mutation in D1684 position of NaV1.7 channel resulted in conversion of aspartate (Asp) into asparagine (Asn). Because of this, TTX toxin cannot get the access on the binding site of this channel and thus unable to block Na+ influx. This mechanism is a remarkable example of an evolutionary process which is known as coevolution. As the number of TTX producing newts increased in the environment, the population of TTX resistant-garter snakes also increased significantly.

D.

N allele in garter snakes would be under the influence of positive selection in those location where only TTX producing newts are present. Because there is no need of TTX resistance in the areas where poisonous newts are absent. Also, if both types of newts are there in an environment, garter snakes have option to feed on non-poisonous snakes. In such an environment, TTX resistance would not be required by the predator.