A Darwinian approach to Huntington's disease: subtle health benefits of a neurological disorder.
Huntington's disease (HD) is a neurodegenerative disorder that, unlike most autosomal dominant disorders, is not being selected against. One explanation for the maintenance of the mutant HD allele is that it is transparent to natural selection because disease symptoms typically occur subsequent to an individual's peak reproductive years. While true, this observation does not explain the population-level increase in HD. The increase in HD is at least partly the result of enhanced fitness: HD+ individuals have more offspring than unaffected relatives. This phenomenon has previously been explained as the result of elevated promiscuity of HD+ individuals. For this to be true, disease symptoms must be expressed during the otherwise asymptomatic peak reproductive years and promiscuity must increase offspring production; however, neither prediction is supported by data. Instead, new data suggest that the mutant HD allele bestows health benefits on its carriers. HD+ individuals show elevated levels of the tumor suppressor protein p53 and experience significantly less cancer than unaffected siblings. We hypothesize that the mutant HD allele elevates carriers' immune activity and thus HD+ individuals are, on average, healthier than HD- individuals during reproductive years. As health and reproductive output are positively related, data suggest a counterintuitive relationship: health benefits may lead to an increased prevalence of Huntington's disease.
Eskenazi
Benjamin R
BR
Department of Biology, Tufts University, Medford, MA 02155, USA.
Wilson-Rich
Noah S
NS
Starks
Philip T
PT
D000483:Alleles; D006801:Humans; D006816:Huntington Disease / Q000453:epidemiology / Q000473:pathology*; D007107:Immune System; D008962:Models, Theoretical; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000453:epidemiology / Q000473:pathology; D012641:Selection, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53