Passage 5: Genetics
A novel drug, Xenaplex, has shown remarkable efficacy in treating a rare genetic
disorder characterized by the accumulation of a toxic metabolite, “Xenic Acid”, in
the body. The disorder is caused by a recessive mutation in the XEN1 gene, which
encodes an enzyme responsible for the breakdown of the metabolite. Xenaplex
is an enantiomerically pure compound that acts as a potent activator of the
XEN1 enzyme, effectively reducing the levels of the toxic metabolite in affected
individuals.
However, clinical trials have revealed that Xenaplex is only effective in a subset of
patients with the disorder. Genetic analysis of responders and non responders
has uncovered a surprising finding: the presence of a specific single nucleotide
polymorphism (SNP) in the XEN1 gene strongly correlates with the drug’s efficacy.
The results of this study are shown below in figures 1 and 2.
Further investigation into the evolutionary history of the XEN1 gene has revealed
that the SNP is a relatively recent mutation, estimated to have arisen approximately
10,000 years ago. The frequency of the SNP varies significantly across different ethnic
groups, with the highest prevalence observed in populations of East Asian descent.
The evolutionary history of the XEN1 SNP suggests that it may have been
subject to:
A) Stabilizing selection
B) Directional selection
C) Disruptive selection
D) Neutral selection
Correct Answer: D
The relatively recent emergence of the SNP and its varying frequency across
different ethnic groups suggest that it may have been subject to neutral selection,
where the allele frequencies are primarily influenced by genetic drift rather than
selective pressures.