The Boi receptor regulates stem cell function by sequestering the diffusible hedgehog ligand.

Although human bitter taste perception is hypothesized to be a dietary adaptation, little is known about genetic signatures of selection and patterns of bitter taste perception variability in ethnically diverse populations with different diets, particularly from Africa. To better understand the genetic basis and evolutionary history of bitter taste sensitivity, we sequenced a 2,975 bp region encompassing TAS2R38, a bitter taste receptor gene, in 611 Africans from 57 populations in West Central and East Africa with diverse subsistence patterns, as well as in a comparative sample of 132 non-Africans. We also examined the association between genetic variability at this locus and threshold levels of phenylthiocarbamide (PTC) bitterness in 463 Africans from the above populations to determine how variation influences bitter taste perception. Here, we report striking patterns of variation at TAS2R38, including a significant excess of novel rare nonsynonymous polymorphisms that recently arose only in Africa, high frequencies of haplotypes in Africa associated with intermediate bitter taste sensitivity, a remarkably similar frequency of common haplotypes across genetically and culturally distinct Africans, and an ancient coalescence time of common variation in global populations. Additionally, several of the rare nonsynonymous substitutions significantly modified levels of PTC bitter taste sensitivity in diverse Africans. While ancient balancing selection likely maintained common haplotype variation across global populations, we suggest that recent selection pressures may have also resulted in the unusually high level of rare nonsynonymous variants in Africa, implying a complex model of selection at the TAS2R38 locus in African populations. Furthermore, the distribution of common haplotypes in Africa is not correlated with diet, raising the possibility that common variation may be under selection due to their role in nondietary biological processes. In addition, our data indicate that novel rare mutations contribute to the phenotypic variance of PTC sensitivity, illustrating the influence of rare variation on a common trait, as well as the relatively recent evolution of functionally diverse alleles at this locus.

In many tissues, the presence of stem cells is inferred by the capacity of the tissue to maintain homeostasis and undergo repair after injury. Isolation of self-renewing cells with the ability to generate the full array of cells within a given tissue strongly supports this idea, but the identification and genetic manipulation of individual stem cells within their niche remain a challenge. Here we present novel methods for marking and genetically altering epithelial follicle stem cells (FSCs) within the Drosophila ovary. Using these new tools, we define a sequential multistep process that comprises transitioning of FSCs from quiescence to proliferation. We further demonstrate that integrins are cell-autonomously required within FSCs to provide directional signals that are necessary at each step of this process. These methods may be used to define precise roles for specific genes in the sequential events that occur during FSC division after a period of quiescence.

Dietary cholesterol levels control follicle stem cell proliferation in the Drosophila ovary via regulation of Hedgehog protein localization.

Bitter taste perception influences human nutrition and health, and the genetic variation underlying this trait may play a role in disease susceptibility. To better understand the genetic architecture and patterns of phenotypic variability of bitter taste perception, we sequenced a 996 bp region, encompassing the coding exon of TAS2R16, a bitter taste receptor gene, in 595 individuals from 74 African populations and in 94 non-Africans from 11 populations. We also performed genotype-phenotype association analyses of threshold levels of sensitivity to salicin, a bitter anti-inflammatory compound, in 296 individuals from Central and East Africa. In addition, we characterized TAS2R16 mutants in vitro to investigate the effects of polymorphic loci identified at this locus on receptor function. Here, we report striking signatures of positive selection, including significant Fay and Wu's H statistics predominantly in East Africa, indicating strong local adaptation and greater genetic structure among African populations than expected under neutrality. Furthermore, we observed a "star-like" phylogeny for haplotypes with the derived allele at polymorphic site 516 associated with increased bitter taste perception that is consistent with a model of selection for "high-sensitivity" variation. In contrast, haplotypes carrying the "low-sensitivity" ancestral allele at site 516 showed evidence of strong purifying selection. We also demonstrated, for the first time, the functional effect of nonsynonymous variation at site 516 on salicin phenotypic variance in vivo in diverse Africans and showed that most other nonsynonymous substitutions have weak or no effect on cell surface expression in vitro, suggesting that one main polymorphism at TAS2R16 influences salicin recognition. Additionally, we detected geographic differences in levels of bitter taste perception in Africa not previously reported and infer an East African origin for high salicin sensitivity in human populations.