Linkage disequilibrium patterns across a recombination gradient in African Drosophila melanogaster

Previous multilocus surveys of nucleotide polymorphism have documented a genome-wide excess of intralocus linkage disequilibrium (LD) in Drosophila melanogaster and D. simulans relative to expectations based on estimated mutation and recombination rates and observed levels of diversity. These studies examined patterns of variation from predominantly non-African populations that are thought to have recently expanded their ranges from central Africa. Here, we analyze polymorphism data from a Zimbabwean population of D. melanogaster, which is likely to be closer to the standard population model assumptions of a large population with constant size. Unlike previous studies, we find that levels of LD are roughly compatible with expectations based on estimated rates of crossing over. Further, a detailed examination of genes in different recombination environments suggests that markers near the telomere of the X chromosome show considerably less linkage disequilibrium than predicted by rates of crossing over, suggesting appreciable levels of exchange due to gene conversion. Assuming that these populations are near mutation-drift equilibrium, our results are most consistent with a model that posits heterogeneity in levels of exchange due to gene conversion across the X chromosome, with gene conversion being a minor determinant of LD levels in regions of high crossing over. Alternatively, if levels of exchange due to gene conversion are not negligible in regions of high crossing over, our results suggest a marked departure from mutation-drift equilibrium (i.e., toward an excess of LD) in this Zimbabwean population. Our results also have implications for the dynamics of weakly selected mutations in regions of reduced crossing over.     

Combining sperm typing and linkage disequilibrium analyses reveals differences in selective pressures or recombination rates across human populations

A previous polymorphism survey of the type 2 diabetes gene CAPN10 identified a segment showing an excess of polymorphism levels in all population samples, coinciding with localized breakdown of linkage disequilibrium (LD) in a sample of Hausa from Cameroon, but not in non-African samples. This raised the possibility that a recombination hotspot is present in all populations and we had insufficient power to detect it in the non-African data. To test this possibility, we estimated the crossover rate by sperm typing in five non-African men; these estimates were consistent with the LD decay in the non-African, but not in the Hausa data. Moreover, resequencing the orthologous region in a sample of Western chimpanzees did not show either an excess of polymorphism level or rapid LD decay, suggesting that the processes underlying the patterns observed in humans operated only on the human lineage. These results suggest that a hotspot of recombination has recently arisen in humans and has reached higher frequency in the Hausa than in non-Africans, or that there is no elevation in crossover rate in any human population, and the observed variation results from long-standing balancing selection.     

Short tandem-repeat polymorphism/alu haplotype variation at the PLAT locus: implications for modern human origins

Two dinucleotide short tandem-repeat polymorphisms (STRPs) and a polymorphic Alu element spanning a 22-kb region of the PLAT locus on chromosome 8p12-q11.2 were typed in 1,287-1,420 individuals originating from 30 geographically diverse human populations, as well as in 29 great apes. These data were analyzed as haplotypes consisting of each of the dinucleotide repeats and the flanking Alu insertion/deletion polymorphism. The global pattern of STRP/Alu haplotype variation and linkage disequilibrium (LD) is informative for the reconstruction of human evolutionary history. Sub-Saharan African populations have high levels of haplotype diversity within and between populations, relative to non-Africans, and have highly divergent patterns of LD. Non-African populations have both a subset of the haplotype diversity present in Africa and a distinct pattern of LD. The pattern of haplotype variation and LD observed at the PLAT locus suggests a recent common ancestry of non-African populations, from a small population originating in eastern Africa. These data indicate that, throughout much of modern human history, sub-Saharan Africa has maintained both a large effective population size and a high level of population substructure. Additionally, Papua New Guinean and Micronesian populations have rare haplotypes observed otherwise only in African populations, suggesting ancient gene flow from Africa into Papua New Guinea, as well as gene flow between Melanesian and Micronesian populations.     

Nucleotide variation at Msn and Alas2, two genes flanking the centromere of the X chromosome in humans

The centromeric region of the X chromosome in humans experiences low rates of recombination over a considerable physical distance. In such a region, the effects of selection may extend to linked sites that are far away. To investigate the effects of this recombinational environment on patterns of nucleotide variability, we sequenced 4581 bp at Msn and 4697 bp at Alas2, two genes situated on either side of the X chromosome centromere, in a worldwide sample of 41 men, as well as in one common chimpanzee and one orangutan. To investigate patterns of linkage disequilibrium (LD) across the centromere, we also genotyped several informative sites from each gene in 120 men from sub-Saharan Africa. By studying X-linked loci in males, we were able to recover haplotypes and study long-range patterns of LD directly. Overall patterns of variability were remarkably similar at these two loci. Both loci exhibited (i) very low levels of nucleotide diversity (among the lowest seen in the human genome); (ii) a strong skew in the distribution of allele frequencies, with an excess of both very-low and very-high-frequency derived alleles in non-African populations; (iii) much less variation in the non-African than in the African samples; (iv) very high levels of population differentiation; and (v) complete LD among all sites within loci. We also observed significant LD between Msn and Alas2 in Africa, despite the fact that they are separated by approximately 10 Mb. These observations are difficult to reconcile with a simple demographic model but may be consistent with positive and/or purifying selection acting on loci within this large region of low recombination.     

Molecular Variation at the Vermilion Locus in Geographically Diverse Populations of Drosophila Melanogaster and D. Simulans

We surveyed nucleotide variation at vermilion in population samples of Drosophila melanogaster from Africa, Asia and the Americas to test the hypothesis that the vermilion gene was a target of balancing selection and to improve our understanding of geographic differentiation. Patterns of polymorphism and divergence showed no evidence for non-neutral evolution. However, the frequency spectrum of polymorphic sites in some non-African samples departed from the neutral equilibrium expectation. Furthermore, there were high levels of linkage disequilibrium in non-African samples, despite apparently high rates of crossing over in the vermilion region. In the absence of comparable data from other loci in these same population samples, we cannot determine whether the unusual patterns of variation at vermilion reflect demographic as opposed to locus-specific events. We found surprisingly high levels of differentiation at vermilion between U.S. and Congo samples of D. simulans. In light of previously published allozyme and mtDNA data that provided no evidence for significant differentiation between African and non-African D. simulans populations, the vermilion data raise the possibility that both mtDNA and allozymes have been influenced by selection.     

Extent of linkage disequilibrium between the androgen receptor gene CAG and GGC repeats in human populations: implications for prostate cancer risk

While studies have implicated alleles at the CAG and GGC trinucleotide repeats of the androgen receptor gene with high-grade, aggressive prostate cancer disease, little is known about the normal range of variation for these two loci, which are separated by about 1.1 kb. More importantly, few data exist on the extent of linkage disequilibrium (LD) between the two loci in different human populations. Here we present data on CAG and GGC allelic variation and LD in six diverse populations. Alleles at the CAG and GGC repeat loci of the androgen receptor were typed in over 1000 chromosomes from Africa, Asia, and North America. Levels of linkage disequilibrium between the two loci were compared between populations. Haplotype variation and diversity were estimated for each population. Our results reveal that populations of African descent possess significantly shorter alleles for the two loci than non-African populations (P<0.0001). Allelic diversity for both markers was higher among African Americans than any other population, including indigenous Africans from Sierra Leone and Nigeria. Analysis of molecular variance revealed that approx. 20% of CAG and GGC repeat variance could be attributed to differences between the populations. All non-African populations possessed the same common haplotype while the three populations of African descent possessed three divergent common haplotypes. Significant LD was observed in our sample of healthy African Americans. The LD observed in the African American population may be due to several reasons; recent migration of African Americans from diverse rural communities following urbanization, recurrent gene flow from diverse West African populations, and admixture with European Americans. This study represents the largest genotyping effort to be performed on the two androgen receptor trinucleotide repeat loci in diverse human populations.     

Inferring human population sizes, divergence times and rates of gene flow from mitochondrial, X and Y chromosome resequencing data

We estimate parameters of a general isolation-with-migration model using resequence data from mitochondrial DNA (mtDNA), the Y chromosome, and two loci on the X chromosome in samples of 25-50 individuals from each of 10 human populations. Application of a coalescent-based Markov chain Monte Carlo technique allows simultaneous inference of divergence times, rates of gene flow, as well as changes in effective population size. Results from comparisons between sub-Saharan African and Eurasian populations estimate that 1500 individuals founded the ancestral Eurasian population approximately 40 thousand years ago (KYA). Furthermore, these small Eurasian founding populations appear to have grown much more dramatically than either African or Oceanian populations. Analyses of sub-Saharan African populations provide little evidence for a history of population bottlenecks and suggest that they began diverging from one another upward of 50 KYA. We surmise that ancestral African populations had already been geographically structured prior to the founding of ancestral Eurasian populations. African populations are shown to experience low levels of mitochondrial DNA gene flow, but high levels of Y chromosome gene flow. In particular, Y chromosome gene flow appears to be asymmetric, i.e., from the Bantu-speaking population into other African populations. Conversely, mitochondrial gene flow is more extensive between non-African populations, but appears to be absent between European and Asian populations.     

Natural selection and population history in the human angiotensinogen gene (AGT): 736 complete AGT sequences in chromosomes from around the world

Several lines of evidence suggest that patterns of genetic variability in the human angiotensinogen gene (AGT) contribute to phenotypic variability in human hypertension. The A(-6) promoter variant of AGT is associated with higher plasma angiotensinogen levels and increased risk of essential hypertension. The geographic distribution of the A(-6) variant leads to the intriguing hypothesis that the G(-6) promoter variant has been selectively advantageous outside Africa. To test these hypotheses, we investigated the roles of population history and natural selection in shaping patterns of genetic diversity in AGT, by sequencing the entire AGT gene (14400 bp) in 736 chromosomes from Africa, Asia, and Europe. We found that the A(-6) variant is present at higher frequency in African populations than in non-African populations. Neutrality tests found no evidence of a departure from selective neutrality, when whole AGT sequences were compared. However, tests restricted to sites in the vicinity of the A(-6)G polymorphism found evidence of a selective sweep. Sliding-window analyses showed that evidence of the sweep is restricted to sites in tight linkage disequilibrium (LD) with the A(-6)G polymorphism. Further, haplotypes carrying the G(-6) variant showed elevated levels of LD, suggesting that they have risen recently to high frequency. Departures from neutral expectation in some but not all regions of AGT indicate that patterns of diversity in the gene cannot be accounted for solely by population history, which would affect all regions equally. Taken together, patterns of genetic diversity in AGT suggest that natural selection has generally favored the G(-6) variant over the A(-6) variant in non-African populations. However, important localized effects may also be present.     

Nucleotide variation of the Est-6 gene region in natural populations of Drosophila melanogaster

We have investigated nucleotide polymorphism in the Est-6 gene region in four samples of Drosophila melanogaster derived from natural populations of East Africa (Zimbabwe), Europe (Spain), North America (California), and South America (Venezuela). There are two divergent sequence types in the North and South American samples, which are not perfectly (North America) or not at all (South America) associated with the Est-6 allozyme variation. Less pronounced or no sequence dimorphism occurs in the European and African samples, respectively. The level of nucleotide diversity is highest in the African sample, lower (and similar to each other) in the samples from Europe and North America, and lowest in the sample from South America. The extent of linkage disequilibrium is low in Africa (1.23% significant associations), but much higher in non-African populations (22.59, 21.45, and 37.68% in Europe, North America, and South America, respectively). Tests of neutrality with recombination are significant in non-African samples but not significant in the African sample. We propose that demographic history (bottleneck and admixture of genetically different populations) is the major factor shaping the nucleotide patterns in the Est-6 gene region. However, positive selection modifies the pattern: balanced selection creates elevated levels of nucleotide variation around functionally important (target) polymorphic sites (RsaI-/RsaI+ in the promoter region and F/S in the coding region) in both African and non-African samples; and directional selection, acting during the geographic expansion phase of D. melanogaster, creates an excess of very similar sequences (RsaI- and S allelic lineages, in the promoter and coding regions, respectively) in the non-African samples.     

Non-African populations of Drosophila melanogaster have a unique origin

Drosophila melanogaster is widely used as a model in DNA variation studies. Patterns of polymorphism have, however, been affected by the history of this species, which is thought to have recently spread out of Africa to the rest of the world. We analyzed DNA sequence variation in 11 populations, including four continental African and seven non-African samples (including Madagascar), at four independent X-linked loci. Variation patterns at all four loci followed neutral expectations in all African populations, but departed from it in all non-African ones due to a marked haplotype dimorphism at three out of four loci. We also found that all non-African populations show the same major haplotypes, though in various frequencies. A parsimonious explanation for these observations is that all non-African populations are derived from a single ancestral population having undergone a substantial reduction of polymorphism, probably through a bottleneck. Less likely alternatives involve either selection at all four loci simultaneously (including balancing selection at three of them), or admixture between two divergent populations. Small but significant structure was observed among African populations, and there were indications of differentiation across Eurasia for non-African ones. Since population history may result in non-equilibrium variation patterns, our study confirms that the search for footprints of selection in the D. melanogaster genome must include a sufficient understanding of its history.     

DNA polymorphism in a worldwide sample of human X chromosomes

DNA sequence data from humans can provide insight into the history of modern humans and the genetic variability in human populations. We report here a study of human DNA sequence variation at an X-linked noncoding region of 10,346 bp. The sample consists of 62 X chromosomes from Africa, Europe, and Asia. Forty-four polymorphic sites were found among the 62 sequences, resulting in 23 different haplotypes. Statistical analyses of the data led to the following inferences. (1) There is strong evidence of human population expansion in the relatively recent past, and this population expansion has had a significant effect on the pattern of polymorphism at this locus. (2) Non-African populations were unlikely to have been derived from a very small number of African lineages. (3) There was considerable geographic subdivision in the ancient human population, which could be an important reason why many studies failed to detect population expansion. (4) The long-term effective population size of humans is between 12,000 and 15,000. And (5) a non-African specific variant was found at a frequency of 35% in non-Africans, an estimate supported by the genotyping of additional 80 non-African and 106 African X chromosomes. This variant could have arisen in Eurasia more than 140,000 years ago, predating the emergence of modern humans. Moreover, this haplotype and all other haplotypes coalesced to the most recent common ancestor of the sample, which was estimated to be older than 490,000 years. Therefore, this region may have a long history in Eurasia.     

African sequence variation accounts for most of the sequence polymorphism in non-African Drosophila melanogaster

We compared the sequence polymorphism of 12 genomic fragments in six geographically dispersed African populations to one European Drosophila melanogaster population. On the basis of one African and one European population half of these fragments have strongly reduced levels of variability outside of Africa. Despite this striking difference in European variation, we detected no significant difference in African variation between the two fragment classes. The joint analysis of all African populations indicated that all high-frequency European alleles are of African origin. We observed a negative Tajima's D in all African populations, with three populations deviating significantly from neutral equilibrium. Low, but statistically significant, population differentiation was observed among the African populations. Our results imply that the population structure and demographic past of African D. melanogaster populations need to be considered for the inference of footprints of selection in non-African populations.     

High diversity of alpha-globin haplotypes in a Senegalese population, including many previously unreported variants.

RFLP haplotypes at the alpha-globin gene complex have been examined in 190 individuals from the Niokolo Mandenka population of Senegal: haplotypes were assigned unambiguously for 210 chromosomes. The Mandenka share with other African populations a sample size-independent haplotype diversity that is much greater than that in any non-African population: the number of haplotypes observed in the Mandenka is typically twice that seen in the non-African populations sampled to date. Of these haplotypes, 17.3% had not been observed in any previous surveys, and a further 19.1% have previously been reported only in African populations. The haplotype distribution shows clear differences between African and non-African peoples, but this is on the basis of population-specific haplotypes combined with haplotypes common to all. The relationship of the newly reported haplotypes to those previously recorded suggests that several mutation processes, particularly recombination as homologous exchange or gene conversion, have been involved in their production. A computer program based on the expectation-maximization (EM) algorithm was used to obtain maximum-likelihood estimates of haplotype frequencies for the entire data set: good concordance between the unambiguous and EM-derived sets was seen for the overall haplotype frequencies. Some of the low-frequency haplotypes reported by the estimation algorithm differ greatly, in structure, from those haplotypes known to be present in human populations, and they may not represent haplotypes actually present in the sample.     

Endothelial nitric oxide synthase intron 4 VNTR gene polymorphisms in European and African populations

Endogenous nitric oxide (NO) is a molecule synthesized by endothelium nitric oxide synthase encoded by the ecNOS gene that plays an important role in regulating the systemic, cardiac and pulmonary circulation. Impairment in NO synthesis has been associated to many cardiovascular disorders, including coronary artery disease and hypertension. We investigated the frequency of the intron 4 VNTR ecNOS gene polymorphism in an Ivorian and an Italian population. The frequencies of the ecNOSb/b, ecNOSa/b and ecNOSa/a genotypes were 0.422, 0.476, and 0.102, respectively, for the Ivorian sample, and 0.712, 0.269, and 0.019, respectively, for the Italian population. The frequencies of ecNOS4b and ecNOS4a alleles were 0.660 and 0.340, respectively, for the Ivorian group, and 0.847 and 0.153, respectively, for the studied Italian population. Genotype frequencies were in Hardy–Weinberg equilibrium in both populations. The Ivorian population showed a significantly higher frequency of the ecNOS4a allele compared to other African and non-African populations, while the Italian sample confirmed the high genetic homogeneity of this polymorphism among Europeans. The maldistribution of endothelial ecNOS polymorphisms between populations could be the results of differential exposure to selection pressures in Africa and during the out-of-Africa expansion.     

The β-esterase Gene Cluster of Drosophila melanogaster: is ψEst-6 a Pseudogene, a Functional Gene, or both?

Pseudogenes have been defined as non-functional sequences of genomic DNA that are originally derived from functional genes, but exhibit degenerative features such as premature stop codons and frameshifts that prevent their expression. However, there is increasing evidence that pseudogenes are often evolutionarily conserved and may have retained some functional role or acquired new ones. Pseudogenes may exhibit non-functional features as well as functional ones. We investigate, as a model case, the beta-esterase gene cluster of Drosophila melanogaster that includes the Est-6 gene and the psiEst-6 putative pseudogene. We study four samples derived from natural populations of east Africa (Zimbabwe), Europe (Spain), North America (California), and South America (Venezuela). The level of nucleotide diversity is higher in Africa than in the non-African populations. There is twice more nucleotide diversity in psiEst-6 than in Est-6. Linkage disequilibrium within the beta-esterase gene cluster is strong in non-African samples, but much lower in Africa. The population recombination rate is the same for psiEst-6 and Est-6 in Africa, but significantly different in non-African samples. Intragenic gene conversion events are detected within Est-6 and, with much higher incidence, within psiEst-6; intergenic gene conversion events are rare. The extensive intragenic gene conversion within psiEst-6 can be explained by the invasion of retrotransposons that promote a form of homology-dependent gene conversion upon excision. Tests of neutrality with recombination are significant for the beta-esterase gene cluster in the non-African populations but not in Africa. The Est-6 gene sequences exhibit a well-known allozyme dimorphic structure. The sequences of psiEst-6 are also dimorphic in North and South America, but they do not correspond at all (South America) or only imperfectly (North America) to the Est-6 allozyme dimorphism. Sequence dimorphism is less pronounced in the European and African samples. We suggest that demographic history (bottleneck and admixture of genetically differentiated populations) is the major factor shaping the nucleotide pattern in the beta-esterase gene cluster. However, there are some clear indications of positive selection shaping the distribution of nucleotide polymorphism within the cluster. Intergenic epistatic selection may play an important role in the evolution of the beta-esterase gene cluster, preserving psiEst-6 from degenerative destruction and reflecting its functional interaction with Est-6. The Est-6 gene cluster of D. melanogaster represents an example of a functionally interacting complex ('intergene') in which two components (Est-6 and psiEst-6) or more are required to perform the final function.     

Linkage Disequilibrium Decay and Past Population History in the Human Genome

The fluctuation of population size has not been well studied in the previous studies of theoretical linkage disequilibrium (LD) expectation. In this study, an improved theoretical prediction of LD decay was derived to account for the effects of changes in effective population sizes. The equation was used to estimate effective population size (N_e) assuming a constant N_e and LD at equilibrium, and these N_e estimates implied the past changes of N_e for a certain number of generations until equilibrium, which differed based on recombination rate. As the influence of recent population history on the N_e estimates is larger than old population history, recent changes in population size can be inferred more accurately than old changes. The theoretical predictions based on this improved expression showed accurate agreement with the simulated values. When applied to human genome data, the detailed recent history of human populations was obtained. The inferred past population history of each population showed good correspondence with historical studies. Specifically, four populations (three African ancestries and one Mexican ancestry) showed population growth that was significantly less than that of other populations, and two populations originated from China showed prominent exponential growth. During the examination of overall LD decay in the human genome, a selection pressure on chromosome 14, the gephyrin gene, was observed in all populations.     

Heterogeneous patterns of variation among multiple human x-linked Loci: the possible role of diversity-reducing selection in non-africans

Studies of human DNA sequence polymorphism reveal a range of diversity patterns throughout the genome. This variation among loci may be due to natural selection, demographic influences, and/or different sampling strategies. Here we build on a continuing study of noncoding regions on the X chromosome in a panel of 41 globally sampled humans representing African and non-African populations by examining patterns of DNA sequence variation at four loci (APXL, AMELX, TNFSF5, and RRM2P4) and comparing these patterns with those previously reported at six loci in the same panel of 41 individuals. We also include comparisons with patterns of noncoding variation seen at five additional X-linked loci that were sequenced in similar global panels. We find that, while almost all loci show a reduction in non-African diversity, the magnitude of the reduction varies substantially across loci. The large observed variance in non-African levels of diversity results in the rejection of a neutral model of molecular evolution with a multi-locus HKA test under both a constant size and a bottleneck model. In non-Africans, some loci harbor an excess of rare mutations over neutral equilibrium predictions, while other loci show no such deviation in the distribution of mutation frequencies. We also observe a positive relationship between recombination rate and frequency spectra in our non-African, but not in our African, sample. These results indicate that a simple out-of-Africa bottleneck model is not sufficient to explain the observed patterns of sequence variation and that diversity-reducing selection acting at a subset of loci and/or a more complex neutral model must be invoked.     

Contrasting Patterns of Nucleotide Sequence Variation at the Glucose Dehydrogenase (Gld) Locus in Different Populations of Drosophila Melanogaster

We have analyzed nucleotide sequence variation at the Glucose dehydrogenase (Gld) locus from four populations of Drosophila melanogaster from four continents. All four population samples show a significant reduction in silent variation compared to the neutral expectation. The levels of silent variation across all four populations are consistent with the predictions of the background selection model; however, Zimbabwe has a remarkably low level of variation. In the face of dramatically reduced silent polymorphism, an amino acid variant, leading to the common allozyme polymorphism at Gld, remains in low to intermediate frequency in all non-African samples. In the Chinese population sample, the ratio of replacement to silent variation is significantly elevated compared to the neutral expectation. The difference in patterns of variation across these population samples suggests that selection on Gld (or the Gld region) has been different in the Chinese population than in the other three.     

African Drosophila melanogaster and D. simulans populations have similar levels of sequence variability, suggesting comparable effective population sizes

Drosophila melanogaster and D. simulans are two closely related species with a similar distribution range. Many studies suggested that D. melanogaster has a smaller effective population size than D. simulans. As most evidence was derived from non-African populations, we readdressed this question by sequencing 10 X-linked loci in five African D. simulans and six African D. melanogaster populations. Contrary to previous results, we found no evidence for higher variability, and thus larger effective population size, in D. simulans. Our observation of similar levels of variability of both species will have important implications for the interpretation of patterns of molecular evolution.     

Population Genomics of Sub-Saharan Drosophila melanogaster: African Diversity and Non-African Admixture

Drosophila melanogaster has played a pivotal role in the development of modern population genetics. However, many basic questions regarding the demographic and adaptive history of this species remain unresolved. We report the genome sequencing of 139 wild-derived strains of D. melanogaster, representing 22 population samples from the sub-Saharan ancestral range of this species, along with one European population. Most genomes were sequenced above 25X depth from haploid embryos. Results indicated a pervasive influence of non-African admixture in many African populations, motivating the development and application of a novel admixture detection method. Admixture proportions varied among populations, with greater admixture in urban locations. Admixture levels also varied across the genome, with localized peaks and valleys suggestive of a non-neutral introgression process. Genomes from the same location differed starkly in ancestry, suggesting that isolation mechanisms may exist within African populations. After removing putatively admixed genomic segments, the greatest genetic diversity was observed in southern Africa (e.g. Zambia), while diversity in other populations was largely consistent with a geographic expansion from this potentially ancestral region. The European population showed different levels of diversity reduction on each chromosome arm, and some African populations displayed chromosome arm-specific diversity reductions. Inversions in the European sample were associated with strong elevations in diversity across chromosome arms. Genomic scans were conducted to identify loci that may represent targets of positive selection within an African population, between African populations, and between European and African populations. A disproportionate number of candidate selective sweep regions were located near genes with varied roles in gene regulation. Outliers for Europe-Africa F_ST were found to be enriched in genomic regions of locally elevated cosmopolitan admixture, possibly reflecting a role for some of these loci in driving the introgression of non-African alleles into African populations.