Limited evidence for adaptive evolution and functional effect of allelic variation at rs702424 in the promoter of the TAS2R16 bitter taste receptor gene in Africa.

Bitter taste perception, mediated by receptors encoded by the TAS2R loci, has important roles in human health and nutrition. Prior studies have demonstrated that nonsynonymous variation at site 516 in the coding exon of TAS2R16, a bitter taste receptor gene on chromosome 7, has been subject to positive selection and is strongly correlated with differences in sensitivity to salicin, a bitter anti-inflammatory compound, in human populations. However, a recent study suggested that the derived G-allele at rs702424 in the TAS2R16 promoter has also been the target of recent selection and may have an additional effect on the levels of salicin bitter taste perception.

Origin and differential selection of allelic variation at TAS2R16 associated with salicin bitter taste sensitivity in Africa.

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.

Evolutionary history and adaptation from high-coverage whole-genome sequences of diverse African hunter-gatherers.

To reconstruct modern human evolutionary history and identify loci that have shaped hunter-gatherer adaptation, we sequenced the whole genomes of five individuals in each of three different hunter-gatherer populations at > 60× coverage: Pygmies from Cameroon and Khoesan-speaking Hadza and Sandawe from Tanzania. We identify 13.4 million variants, substantially increasing the set of known human variation.

Structural diversity and African origin of the 17q21.31 inversion polymorphism.

The 17q21.31 inversion polymorphism exists either as direct (H1) or inverted (H2) haplotypes with differential predispositions to disease and selection. We investigated its genetic diversity in 2,700 individuals, with an emphasis on African populations.

Patterns of ancestry, signatures of natural selection, and genetic association with stature in Western African pygmies.

African Pygmy groups show a distinctive pattern of phenotypic variation, including short stature, which is thought to reflect past adaptation to a tropical environment. Here, we analyze Illumina 1M SNP array data in three Western Pygmy populations from Cameroon and three neighboring Bantu-speaking agricultural populations with whom they have admixed. We infer genome-wide ancestry, scan for signals of positive selection, and perform targeted genetic association with measured height variation.

Evolution of functionally diverse alleles associated with PTC bitter taste sensitivity in Africa.

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.

Characterization of genetic variation and natural selection at the arylamine N-acetyltransferase genes in global human populations.

Unlabelled: Functional variability at the arylamine N-acetyltransferase genes is associated with drug response in humans and may have been adaptive in the past owing to selection pressure from diet and exposure to toxins during human evolution.

Aims: We have characterized nucleotide variation at the NAT1 and NAT2 genes, and at the NATP1 pseudogene in global human populations, including many previously under-represented African populations, in order to identify potential functional variants and to understand the role that natural selection has played in shaping variation at these loci in globally diverse populations.

Materials & Methods: We have resequenced approximately 2800 bp for each of the NAT1 and NAT2 gene regions, as well as the pseudogene NATP1, in 197 African and 132 nonAfrican individuals.

Genome-wide patterns of population structure and admixture in West Africans and African Americans.

Quantifying patterns of population structure in Africans and African Americans illuminates the history of human populations and is critical for undertaking medical genomic studies on a global scale. To obtain a fine-scale genome-wide perspective of ancestry, we analyze Affymetrix GeneChip 500K genotype data from African Americans (n = 365) and individuals with ancestry from West Africa (n = 203 from 12 populations) and Europe (n = 400 from 42 countries). We find that population structure within the West African sample reflects primarily language and secondarily geographical distance, echoing the Bantu expansion.

The genetic structure and history of Africans and African Americans.

Africa is the source of all modern humans, but characterization of genetic variation and of relationships among populations across the continent has been enigmatic. We studied 121 African populations, four African American populations, and 60 non-African populations for patterns of variation at 1327 nuclear microsatellite and insertion/deletion markers. We identified 14 ancestral population clusters in Africa that correlate with self-described ethnicity and shared cultural and/or linguistic properties.