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Analytical and statistical stochastic approaches are used to model the dispersion of monogenic variants through large populations. These approaches are used to quantify the magnitude of the selective advantage of a monogenic heterozygous variant in the presence of a homozygous disadvantage. Dunbar's results regarding the cognitive upper limit of the number of stable social relationships that humans can maintain are used to determine a realistic effective community size from which an individual can select mates. By envisaging human community structure as a network where social proximity rather than physical geography predominates, a significant simplification is achieved, implicitly accounting for the effects of migration and consanguinity, and with population structure and genetic drift becoming emergent features of the model. Effective community size has a dramatic effect on the probability of establishing beneficial alleles. It also affects the eventual equilibrium values that are reached in the case of variants conferring a heterozygous selective advantage, but a homozygous disadvantage, as in the case of cystic fibrosis and sickle cell disease. The magnitude of this selective advantage can then be estimated based on observed occurrence levels of a specific allele in a population, without requiring prior information regarding its phenotypic manifestation.

The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes.