The Admixture Structure and Genetic Variation of the Archipelago of Cape Verde and Its Implications for Admixture Mapping Studies

Recently admixed populations offer unique opportunities for studying human history and for elucidating the genetic basis of complex traits that differ in prevalence between human populations. Historical records, classical protein markers, and preliminary genetic data indicate that the Cape Verde islands in West Africa are highly admixed and primarily descended from European males and African females. However, little is known about the variation in admixture levels, admixture dynamics and genetic diversity across the islands, or about the potential of Cape Verde for admixture mapping studies. We have performed a detailed analysis of phenotypic and genetic variation in Cape Verde based on objective skin color measurements, socio-economic status (SES) evaluations and data for 50 autosomal, 34 X-chromosome, and 21 non-recombinant Y-chromosome (NRY) markers in 845 individuals from six islands of the archipelago. We find extensive genetic admixture between European and African ancestral populations (mean West African ancestry = 0.57, sd = 0.08), with individual African ancestry proportions varying considerably among the islands. African ancestry proportions calculated with X and Y-chromosome markers confirm that the pattern of admixture has been sex-biased. The high-resolution NRY-STRs reveal additional patterns of variation among the islands that are most consistent with differentiation after admixture. The differences in the autosomal admixture proportions are clearly evident in the skin color distribution across the islands (Pearson r = 0.54, P-value<2e–16). Despite this strong correlation, there are significant interactions between SES and skin color that are independent of the relationship between skin color and genetic ancestry. The observed distributions of admixture, genetic variation and skin color and the relationship of skin color with SES relate to historical and social events taking place during the settlement history of Cape Verde, and have implications for the design of association studies using this population.     

Y-chromosome lineages in Cabo Verde Islands witness the diverse geographic origin of its first male settlers

The Y-chromosome haplogroup composition of the population of the Cabo Verde Archipelago was profiled by using 32 single-nucleotide polymorphism markers and compared with potential source populations from Iberia, west Africa, and the Middle East. According to the traditional view, the major proportion of the founding population of Cabo Verde was of west African ancestry with the addition of a minor fraction of male colonizers from Europe. Unexpectedly, more than half of the paternal lineages (53.5%) of Cabo Verdeans clustered in haplogroups I, J, K, and R1, which are characteristic of populations of Europe and the Middle East, while being absent in the probable west African source population of Guiné-Bissau. Moreover, a high frequency of J* lineages in Cabo Verdeans relates them more closely to populations of the Middle East and probably provides the first genetic evidence of the legacy of the Jews. In addition, the considerable proportion (20.5%) of E3b(xM81) lineages indicates a possible gene flow from the Middle East or northeast Africa, which, at least partly, could be ascribed to the Sephardic Jews. In contrast to the predominance of west African mitochondrial DNA haplotypes in their maternal gene pool, the major west African Y-chromosome lineage E3a was observed only at a frequency of 15.9%. Overall, these results indicate that gene flow from multiple sources and various sex-specific patterns have been important in the formation of the genomic diversity in the Cabo Verde islands.An erratum to this article can be found at     

Population database of STRs in West Africa: a genetic study of TPOX, HUMVWA31/A, HUMTH01, and CYP19

Four tetrameric STRs (TPOX, HUMVWA31/A, HUMTH01, and CYP19) were analysed in a West African population (Cabo Verde). No significant deviations from Hardy–Weinberg proportions were observed, either in conventional or exact tests. Pairwise comparisons confirmed allelic independence for all the combinations of loci. Data is provided for the first time about CYP19 in Black populations. In comparisons between African and Afro‐American populations, significant frequency differences for several alleles at the TH01 and VWA31/A loci were observed. The allele frequencies provided in this study contribute to a better knowledge of the variability of these markers among the main human groups, especially in the context of Subsaharan African populations. This revised version was published online in July 2006 with corrections to the Cover Date.     

An exceptional case of historical outbreeding in African sable antelope populations

Empirical investigations of intraspecific outbreeding and subsequent introgressive hybridization in natural populations are rare, particularly among conspecific populations of large mammals. Using mitochondrial DNA data [partial control region (496 basepairs - bp) and cytochrome b gene (343 bp) sequences analysed from 95 individuals representing 17 sampling locations scattered through the African miombo (Brachystegia) woodland ecosystem] and phylogeographical statistical procedures (gene genealogy, nested cladistic and admixture proportion analyses), we (i) give a detailed dissection of the geographical genetic structure of Hippotragus niger; (ii) infer the processes and events potentially involved in the population history; and (iii) trace extensive introgressive hybridization in the species. The present-day sable antelope population shows a tripartite pattern of genetic subdivision representing West Tanzanian, Kenya/East Tanzanian and Southern Africa locations. Nested clade analysis revealed that past allopatric fragmentation, caused probably by habitat discontinuities associated with the East African Rift Valley system, together with intermediary episodic long-distance colonization and restricted, recurrent gene flow have played an predominant role in shaping the extent of maternal genetic diversity (10.4%) and population structure. An extensive (average rate of admixture = 20.0%), but geographically circumscribed and unidirectional hybridization event in the past was inferred, resulting in an extreme (the highest discovered so far in mammals) intraspecific difference of 18.2% among morphologically monotypic sable antelopes from West Tanzania. The results are used to provide an evolutionary framework within which taxonomic implications and conservation decisions can be evaluated.     

Pre‐Hispanic Mesoamerican demography approximates the present‐day ancestry of Mestizos throughout the territory of Mexico

Over the last 500 years, admixture among Amerindians, Europeans, and Africans, principally, has come to shape the present‐day gene pool of Mexicans, particularly Mestizos, who represent about 93% of the total Mexican population. In this work, we analyze the genetic data of 13 combined DNA index system‐short tandem repeats (CODIS‐STRs) in 1,984 unrelated Mestizos representing 10 population samples from different regions of Mexico, namely North, West, Central, and Southeast. The analysis of molecular variance (AMOVA) test demonstrated low but significant differentiation among Mestizos from different regions (F_ST = 0.34%; P = 0.0000). Although the spatial analysis of molecular variance (SAMOVA) predicted clustering Mestizo populations into four well‐delimited groups, the main differentiation was observed between Northwest when compared with Central and Southeast regions. In addition, we included analysis of individuals of Amerindian (Purepechas), European (Huelva, Spain), and African (Fang) origin. Thus, STRUCTURE analysis was performed identifying three well‐differentiated ancestral populations (k = 3). STRUCTURE results and admixture estimations by means of LEADMIX software in Mestizo populations demonstrated genetic heterogeneity or asymmetric admixture throughout Mexico, displaying an increasing North‐to‐South gradient of Amerindian ancestry, and vice versa regarding the European component. Interestingly, this distribution of Amerindian ancestry roughly reflects pre‐Hispanic Native‐population density, particularly toward the Mesoamerican area. The forensic, epidemiological, and evolutionary implications of these findings are discussed herein. Am J Phys Anthropol 2009. © 2009 Wiley‐Liss, Inc.     

Genetic structure of kestrel populations and colonization of the Cape Verde archipelago

Genetic diversity and population structure were studied in eight populations of the kestrel Falco tinnunculus to identify the genetic consequences of spatial distribution and to infer the colonization patterns of the Cape Verde archipelago. We studied genetic differentiation and gene flow among seven island populations and one mainland population using nine microsatellite loci. Within the archipelago, differentiation was strong and genetic diversity and heterozygosity were low but variable among populations. Two subspecies F. tinnunculus neglectus on the northwestern islands and F. tinnunculus alexandri on all the other islands were identified as genetically distinct units. F. t. alexandri could be further separated into two groups on eastern and southern islands. Populations are probably founded by birds originating from the mainland. Immigration is more likely to the eastern and southern populations, whereas the northwestern islands with the lowest genetic diversity and highest differentiation are likely to exhibit fewer founding events by immigrants. The number of founding events on each island may depend not only on geographical distance to neighbouring populations, but also on directional immigration due to the northeastern trade winds. This may explain differences in genetic differentiation and diversity between populations and subspecies and may enable allopatric speciation.     

A genomewide admixture mapping panel for Hispanic/Latino populations

Admixture mapping (AM) is a promising method for the identification of genetic risk factors for complex traits and diseases showing prevalence differences among populations. Efficient application of this method requires the use of a genomewide panel of ancestry-informative markers (AIMs) to infer the population of origin of chromosomal regions in admixed individuals. Genomewide AM panels with markers showing high frequency differences between West African and European populations are already available for disease-gene discovery in African Americans. However, no such a map is yet available for Hispanic/Latino populations, which are the result of two-way admixture between Native American and European populations or of three-way admixture of Native American, European, and West African populations. Here, we report a genomewide AM panel with 2,120 AIMs showing high frequency differences between Native American and European populations. The average intermarker genetic distance is ~1.7 cM. The panel was identified by genotyping, with the Affymetrix GeneChip Human Mapping 500K array, a population sample with European ancestry, a Mesoamerican sample comprising Maya and Nahua from Mexico, and a South American sample comprising Aymara/Quechua from Bolivia and Quechua from Peru. The main criteria for marker selection were both high information content for Native American/European ancestry (measured as the standardized variance of the allele frequencies, also known as "f value") and small frequency differences between the Mesoamerican and South American samples. This genomewide AM panel will make it possible to apply AM approaches in many admixed populations throughout the Americas.     

Mitochondrial DNA (mtDNA) haplotypes reveal maternal population genetic affinities of Sea Island Gullah-speaking African Americans

To better understand the population substructure of African Americans living in coastal South Carolina, we used restriction site polymorphisms and an insertion/deletion in mitochondrial DNA (mtDNA) to construct seven-position haplotypes across 1,395 individuals from Sierra Leone, Africa, from U.S. European Americans, and from the New World African-derived populations of Jamaica, Gullah-speaking African Americans of the South Carolina Sea Islands (Gullahs), African Americans living in Charleston, South Carolina, and West Coast African Americans. Analyses showed a high degree of similarity within the New World African-derived populations, where haplotype frequencies and diversities were similar. Phi-statistics indicated that very little genetic differentiation has occurred within New World African-derived populations, but that there has been significant differentiation of these populations from Sierra Leoneans. Genetic distance estimates indicated a close relationship of Gullahs and Jamaicans with Sierra Leoneans, while African Americans living in Charleston and the West Coast were progressively more distantly related to the Sierra Leoneans. We observed low maternal European American admixture in the Jamaican and Gullah samples (m = 0.020 and 0.064, respectively) that increased sharply in a clinal pattern from Charleston African Americans to West Coast African Americans (m = 0.099 and 0.205, respectively). The appreciably reduced maternal European American admixture noted in the Gullah indicates that the Gullah may be uniquely situated to allow genetic epidemiology studies of complex diseases in African Americans with low European American admixture.     

Mitochondrial DNA patterns in the Macaronesia islands: Variation within and among archipelagos

Macaronesia covers four Atlantic archipelagos: the Azores, Madeira, the Canary Islands, and the Cape Verde islands. When discovered by Europeans in the 15th century, only the Canaries were inhabited. Historical reports highlight the impact of Iberians on settlement in Macaronesia. Although important differences in their settlement are documented, its influence on their genetic structures and relationships has yet to be ascertained. In this study, the hypervariable region I (HVRI) sequence and coding region polymorphisms of mitochondrial DNA (mtDNA) in 623 individuals from the Azores (120) and Canary Islands (503) were analyzed. Combined with published data, these give a total of 1,542 haplotypes from Macaronesia and 1,067 from the Iberian Peninsula. The results obtained indicate that Cape Verde is the most distinctive archipelago, with an mtDNA pool composed almost exclusively of African lineages. However, the other archipelagos present an mtDNA profile dominated by the presence of West‐Eurasian mtDNA haplogroups with African lineages present in varying proportions. Moreover, no signs of integration of typical Canarian U6 lineages in the other archipelagos were detected. The four Macaronesia archipelagos currently have differentiated genetic profiles, and the Azores present the highest intra‐archipelago differentiation and the lowest values of diversity. The analyses performed show that the present‐day genetic profile of the Macaronesian archipelagos was mainly determined by the initial process of settlement and further microdifferentiation probably as a consequence of the small population size of some islands. Moreover, contacts between archipelagos seem to have had a low impact on the mtDNA genetic pool of each archipelago. Am J Phys Anthropol, 2010. © 2009 Wiley‐Liss, Inc.     

Exploring Population Admixture Dynamics via Empirical and Simulated Genome-wide Distribution of Ancestral Chromosomal Segments

The processes of genetic admixture determine the haplotype structure and linkage disequilibrium patterns of the admixed population, which is important for medical and evolutionary studies. However, most previous studies do not consider the inherent complexity of admixture processes. Here we proposed two approaches to explore population admixture dynamics, and we demonstrated, by analyzing genome-wide empirical and simulated data, that the approach based on the distribution of chromosomal segments of distinct ancestry (CSDAs) was more powerful than that based on the distribution of individual ancestry proportions. Analysis of 1,890 African Americans showed that a continuous gene flow model, in which the African American population continuously received gene flow from European populations over about 14 generations, best explained the admixture dynamics of African Americans among several putative models. Interestingly, we observed that some African Americans had much more European ancestry than the simulated samples, indicating substructures of local ancestries in African Americans that could have been caused by individuals from some particular lineages having repeatedly admixed with people of European ancestry. In contrast, the admixture dynamics of Mexicans could be explained by a gradual admixture model in which the Mexican population continuously received gene flow from both European and Amerindian populations over about 24 generations. Our results also indicated that recent gene flows from Sub-Saharan Africans have contributed to the gene pool of Middle Eastern populations such as Mozabite, Bedouin, and Palestinian. In summary, this study not only provides approaches to explore population admixture dynamics, but also advances our understanding on population history of African Americans, Mexicans, and Middle Eastern populations.     

Assessing introgression of Sahelian zebu genes into native Bos taurus breeds in Burkina Faso

A total of 350 samples were analyzed to estimate zebu gene proportions into two different taurine cattle breeds of Burkina Faso (Lobi and N’Dama) using 38 microsatellites and various statistical methodologies. West African and East African zebu samples were sequentially used as reference parental populations. Furthermore, N’Dama cattle from Congo, the composite South African Bonsmara cattle breed and a pool of European cattle were used successively as second parental populations. Independently of the methodology applied: (a) the use of West African zebu samples gave higher admixture coefficients than the East African zebu; (b) the higher zebu proportions were estimated when the European cattle was used as parental population 2; and (c) the use of the N’Dama population from Congo as parental population 2 gave the more consistent zebu proportion estimates for both the Lobi and the N’Dama breeds. In any case, the zebu admixture proportions estimated were not negligible and were always higher in the N’Dama cattle than in the Lobi cattle of Burkina Faso. This suggested that the introgression of Sahelian zebu genes into the taurine cattle of Southern West Africa can follow a complex pattern that can depend on local agro-ecological features. The current research pointed out that the estimation of admixture coefficients is highly dependent on both the assumptions underlying the methodologies applied and the selection of parental populations. Our analyses suggest that either too high or nil genetic identity between the parental and the expectedly derived populations must be avoided.     

Population structure in African Drosophila melanogaster revealed by microsatellite analysis

Tropical sub-Saharan regions are considered to be the geographical origin of Drosophila melanogaster. Starting from there, the species colonized the rest of the world after the last glaciation about 10 000 years ago. Consistent with this demographic scenario, African populations have been shown to harbour higher levels of microsatellite and sequence variation than cosmopolitan populations. Nevertheless, limited information is available on the genetic structure of African populations. We used X chromosomal microsatellite variation to study the population structure of D. melanogaster populations using 13 sampling sites in North, West and East Africa. These populations were compared to six European and one North American population. Significant population structure was found among African D. melanogaster populations. Using a Bayesian method for inferring population structure we detected two distinct groups of populations among African D. melanogaster. Interestingly, the comparison to cosmopolitan D. melanogaster populations indicated that one of the divergent African groups is closely related to cosmopolitan flies. Low, but significant levels of differentiation were observed for sub-Saharan D. melanogaster populations from West and East Africa.     

Phylogeography of a Marine Insular Endemic in the Atlantic Macaronesia: The Azorean Barnacle,Megabalanus azoricus (Pilsbry, 1916)

The Azorean barnacle, Megabalanus azoricus (Pilsbry, 1916), is a Macaronesian endemic whose obscure taxonomy and the unknown relationships among forms inhabiting isolated Northern Atlantic oceanic islands is investigated by means of molecular analysis herein. Mitochondrial data from the 16S rRNA and COX1 genes support its current species status, tropical ancestry, and the taxonomic homogeneity throughout its distribution range. In contrast, at the intraspecific level and based on control region sequences, we detected an overall low level of genetic diversity and three divergent lineages. The haplogroups α and γ were sampled in the Azores, Madeira, Canary, and Cabo Verde archipelagos; whereas haplogroup β was absent from Cabo Verde. Consequently, population analysis suggested a differentiation of the Cabo Verde population with respect to the genetically homogenous northern archipelagos generated by current oceanographic barriers. Furthermore, haplogroup α, β, and γ demographic expansions occurred during the interglacial periods MIS5 (130 Kya - thousands years ago -), MIS3 (60 Kya), and MIS7 (240 Kya), respectively. The evolutionary origin of these lineages is related to its survival in the stable southern refugia and its demographic expansion dynamics are associated with the glacial-interglacial cycles. This phylogeographic pattern suggests the occurrence of genetic discontinuity informative to the delimitation of an informally defined biogeographic entity, Macaronesia, and its generation by processes that delineate genetic diversity of marine taxa in this area.     

The St. Lawrence Island Eskimos: genetic variation and genetic distance

The Eskimos of St. Lawrence Island have been typed for genetic variation at 44 discrete genetic loci. Three private polymorphisms, at the 2,3-diphosphoglycerate mutase, peptidase B, and purine nucleoside phosphorylase loci, have been observed, which may be useful in future studies of genetic relationships between Eskimos and other circumpolar populations. Genetic distance analysis reveals a close relationship between the St. Lawrence Island Eskimos and other Eskimo populations and that the Eskimo populations form a distinct cluster from Amerindian populations. The St. Lawrence Island Eskimos appear to be more similar to Asiatic Eskimos than to other groups. Caucasian admixture in this population is estimated to be between 2 and 7%.     

Frequency of the CCR5-delta32 mutation in the Atlantic island populations of Madeira, the Azores, Cabo Verde, and São Tomé e Príncipe

There is evidence that the CCR5-delta32 mutation confers protection against HIV-1 infection to homozygous individuals. It is believed that this mutation spread through Europe with the Vikings and that it has been subjected to positive selection, leading to a high frequency in Europe (approximately 10%). We carried out the present study to determine the 32-bp deletion allele and genotype frequencies of the CCR5 gene (CCR5-delta32) in the Atlantic island populations of Madeira, the Azores, Cabo Verde, and S?o Tomé e Principe. These Atlantic archipelagos were all colonized by the Portuguese in the 15th and 16th centuries, but the latter two received most of their settlers from the West African coast. The frequency of the CCR5-delta32 mutation varies between 0% in S?o Tomé e Príncipe and 16.5% in the Azores. The Azores Islands have one of the highest frequencies of homozygotes found in Europe (4.8%). There are significant differences (P < 0.05) between some of these populations, for example, between S?o Tomé e Príncipe and Cabo Verde, and even within populations (e.g., Portugal, Madeira, and the Azores).     

Historical and contemporary population genetic connectivity of the European short-snouted seahorse Hippocampus hippocampus and implications for management

This first genetic study of Hippocampus hippocampus covers the species' entire geographic range and employs two mtDNA markers (control region and cytochrome b) to establish patterns of population structuring. A total of 255 specimens from 21 locations were used to obtain 89 concatenated haplotypes. The common haplotype was present in all but one population, however, most haplotypes were unique. The haplotype network had a star-like construction, suggesting expansion from a bottleneck event. F(ST) and AMOVA revealed population subdivision into three geographic regions (English Channel + Bay of Biscay, Mediterranean Sea + Atlantic Ocean Iberian coast + Macaronesian Islands, and West Africa) with barriers to gene flow indentified at Cape Finisterre and the Cape Verde frontal zone. Neutrality tests and nested clade analysis suggest a complex demographic history, with both historic events and contemporary processes shaping patterns of genetic differentiation. The genetic population subdivision detected in this study indicates that H. hippocampus should be managed as three separate units. This is especially pertinent as H. hippocampus populations within the West African region are the only ones known to be specifically targeted for exploitation.     

Extremely low genetic diversity and extensive genetic admixture at the northern range margins of Bombax ceiba

Understanding the evolutionary processes in species at the margins of their range is of great significance, because marginal populations may harbor local adaptations and will initiate further expansion in response to changes in the environment. Here we examined genetic variation in two nuclear genes and one chloroplast intergenic spacer in 13 northern marginal populations and one geographically central population of Bombax ceiba, a tree distributed mainly in tropical regions. Our results revealed an extremely low level of genetic diversity in each population at the northern margin of its range and strong genetic differentiation between southern China and South Asia. Cultivated and natural populations showed no significant differences in genetic variability. Genetic admixture in a nuclear gene was detected in 10 of the 13 populations at the northern margin of their range. The founder effect, in which a small number of individuals colonize the northern margins of its range, may explain the extremely low genetic diversity. During the establishment of new populations, different source populations may mix and undergo further genetic drift and differentiation. This study indicates that patterns of genetic diversity in tropical species at the margin of their range may also be severely influenced by founder effects.     

Possible ancestral structure in human populations

Determining the evolutionary relationships between fossil hominid groups such as Neanderthals and modern humans has been a question of enduring interest in human evolutionary genetics. Here we present a new method for addressing whether archaic human groups contributed to the modern gene pool (called ancient admixture), using the patterns of variation in contemporary human populations. Our method improves on previous work by explicitly accounting for recent population history before performing the analyses. Using sequence data from the Environmental Genome Project, we find strong evidence for ancient admixture in both a European and a West African population (p ≈ 10⁻⁷), with contributions to the modern gene pool of at least 5%. While Neanderthals form an obvious archaic source population candidate in Europe, there is not yet a clear source population candidate in West Africa.     

Estimates of African, European and Native American ancestry in Afro-Caribbean men on the island of Tobago

BACKGROUND/AIMS: The Tobago Afro-Caribbean population is a valuable resource for studying the genetics of diseases that show significant differences in prevalence between populations of African descent and populations of other ancestries. Empirical confirmation of low European and Native American admixture may help in clarifying the ethnic variation in risk for such diseases. We hypothesize that the degree of European and Native American admixture in the Tobago population is low. METHODS: Admixture was estimated in a random sample of 220 men, from a population-based prostate cancer screening survey of 3,082 Tobago males, aged 40 to 79 years. We used a set of six autosomal markers with large allele frequency differences between the major ethnic populations involved in the admixture process, Europeans, Native Americans and West Africans. RESULTS: The ancestral proportions of Tobago population are estimated as 94.0+/-1.2% African, 4.6+/-3.4% European and 1.4+/-3.6% Native American. CONCLUSIONS: We conclude that Tobago Afro-Caribbean men are predominantly of West African ancestry, with minimal European and Native American admixture. The Tobago population, thus, may carry a higher burden of high-risk alleles of African origin for certain diseases than the more admixed African-American population. Conversely, this population may benefit from a higher prevalence of protective alleles of African origin.