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A review in the latest Medical Hypotheses discusses the evolutionary basis of Huntington’s disease, a rare dominant genetic disorder affecting around 3-7 per 100,000 people of European origin. Individuals carrying a single mutant copy of the huntingtin gene (HD+) typically suffer serious neurological and physical problems beginning between age 35 and 50, and killing them within 10 to 15 years.

From an evolutionary POV, the existence of Huntington’s disease alleles seems straightforward: the disease typically hits people after their reproductive years, and due to the nature of the mutation (an expansion of a polyglutamine repeat) the incidence of new sporadic mutations is pretty high – around 5% of cases are due to new mutations.

However, it appears that another factor is in play. The review lists five studies indicating greater reproductive fitness in HD+ individuals, who apparently produce between 1.14 and 1.34 children for every child borne by unaffected sibling controls. Apparently the popular theory is that this increased fertility is due to heightened promiscuity in HD+ individuals, presumably due to some early-onset sub-clinical psychological manifestation of the disease.

The authors of this review pooh-pooh the promiscuity hypothesis, pointing out the lack of evidence that most HD+ individuals suffer any neurological alterations during their reproductive years, and also arguing that promiscuity doesn’t necessarily increase reproductive fitness. Instead, they point to a single study indicating substantially decreased cancer risks in HD+ subjects. Their hypothesis is not that this reduced cancer risk itself increases reproductive output, but rather that this reflects increased immune surveillance and vigour that would be expected to increase overall health and attractiveness in young HD+ individuals.

There is lengthy speculation about a link between the huntingtin protein and p53, a well-known tumour-suppressor. In support of their argument for a general immune boost in HD+ carriers they cite increased rates of type 2 diabetes and Alzheimer’s, which both have a substantial auto-immune component.

Like most adaptive Just So stories the immune-boosting hypothesis is almost certainly wrong, and both it and the promiscuity story have essentially nothing in the way of direct evidence. Still, the increased fertility rates in HD+ individuals – which seem fairly well-supported – scream out for an explanation. With luck, someone will eventually carry out some actual experiments to figure out what that explanation is.

(Republished from GNXP.com by permission of author or representative)
 
• Category: Science • Tags: Disease, Evolution 
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