markers allowed us to identify which parental populations contributed heterogeneously to populations in the Americas. Discussion The goal of this analysis was to investigate the differences in within-Africa genetic ancestry between the admixed groups of the Americas with African origin. Continental ancestry We first considered how maternal and paternal continental ancestries that reflect gender-specific admixture patterns at the group level are correlated with the average individual ancestry represented by AIMs for each African-derived American popula- tion. Using mtDNA and NRY, we confirmed the presence of sex- specific admixture as well as the existence of differences across the Americas in continental admixture that are largely due to maternal contributions [4], [7]. So, while South American populations of both primarily African and European ancestry are highly admixed, in North America it is only the African American population that is highly admixed (Figure 1) compared to European Americans (Figure S1 in File S3). Based on AIMs and comparisons with other admixed popula- tions, Philadelphia African Americans are, as expected, signifi- cantly more admixed than Senegalese or Nigerians [47] (average individual African ancestry in Philadelphia: 79.1%, Senegalese/ Nigerians ,95%), and the admixture profile resembles that of other African American groups in the US [47], [48] (79–83%). More importantly, we confirmed that the combined ancestry information is largely captured by uniparental markers and these can therefore not only provide insights into gender-specific admixture processes but also inform us about the source of the founding populations that contribute to admixture. Maternal ancestry within Africa Africa is the most genetically diverse of the continents [49]. Since distinct groups of the Americas could have drawn the African portion of their ancestry from different populations within Africa, African ‘‘admixture’’ (in addition to continental admixture) can add to the diversity of these groups when population stratification is considered. In order to assess the within-Africa ancestry of African-derived Americans, possible source popula- tions need to be defined from a thoroughly sampled genetic variation of Africa. We used mtDNA to evaluate the genomic variation contributed by populations from distinct African regions to American populations, since large source African mtDNA variation is already in place. We assembled a comprehensive database of published mtDNA profiles, focusing on the African continent and admixed African- American populations. We have used this database to estimate the genetic ancestry and admixture proportions based on our well-defined map of correlation between geography-language- ethnicity and phylogenetically-relevant genetic distances. Our initial choice of separating Africa into geographically discrete regions was based on published work that reports correlation between genetic and geographic/linguistic distances in African populations [50]. Additionally, we separated Bantu and Pygmy, since the Bantu expansion was shown to weaken the language- genetic distance correlation [50]. Also, Pygmy and Bantu populations were shown to be distinct in their mtDNA signature [51], although Bantu males reduced this difference in NRY through an asymmetrical gene flow between Bantu males and Pygmy females [52]. Within-Africa Ancestry Within-Africa ancestry of populations of African descent Our results allowed us to narrow down the founding groups that play a significant role in the within-Africa ancestry of African Americans. These groups are ancestrally found in the W, WC, SW, and SE regions of Africa, with the WC group split between Bantu and non-Bantu populations. There is a decreasing contribution from W/WC Africa in the order of C.N.S America such that the contribution of W/WC Africa is the greatest in the Caribbean (,75%) and Cuba (,79%), less in the United States (,68%) and Philadelphia (,59%), and even less in Brazil (,41%) (the exception being Colombia with ,63%). This is in agreement with published literature (Salas et al., [3]) that investigated the populations of the United States, the Caribbean, and Brazil and defined the African groups as W (our W and WC) and WC (our SW/WC Bantu and Sa˜o Tome´ e Pr´ıncipe), using 27 African haplotypes (see comparison in Figure 3a). Additionally, we observed a significant contribution from SE Africa to the African mtDNA pool of Brazil and Colombia (14% and 10%, respectively), perhaps because of greater phylogenetic resolution of our study (we defined 429 haplotypes). While the contribution of SE Africans to the Brazilian and Colombian pools was not reported in [3], it is corroborated by previous reports on Brazilians from Sa˜o Paulo (,12%) [6] and historical resources. By undertaking a detailed phylogenetic analysis, we were able to further separate the contribution by various African regions into 7-10 genetically diverse groups/regions and estimate the propor- tions by which these regions contributed to the admixed African and American populations. We paid particular attention to the W/WC African variation, since West Africa was historically considered to be a highly significant source of slaves to North America. First, we compared the African profiles of the admixed populations of archipelagos off the W/WC Africa coast (Cabo Verde and Sa˜o Tome´ e Pr´ıncipe), followed by the Americas (USA, Philadelphia, Cuba, Caribbean islands, Colombia, and Brazil). The population of Cabo Verde is mainly drawn from the Senegambia/Guinea/Windward coast directly neighboring the archipelago. In Sa˜o Tome´ e Pr´ıncipe, ,40% of mtDNAs were drawn from nearby Gabon and Equatorial Guinea and Angola, and ,60% from the West coast region (or possibly Cabo Verde). Both of these regions were major sources of slaves for Portuguese colonies at the time of populating this archipelago (Figure S6 in File S3), connecting it to the parental African regions not only by a geographical distance but also by the Portuguese control of both the source and target regions. Colonial systems and genetic ancestry Detailed analysis of the populations of the New World revealed a marked difference in the source of African mtDNAs between North and South America, Caribbean, and neighboring regions. Closer examination of these within-Africa ancestry estimates reinforced the strong relationship between the colonial systems of Africa and the Americas and present-day genomic ancestry. The Portuguese were the pioneers of the slave trade and the main importers of African slaves into Brazil. The Portuguese started bringing slaves into Brazil by the end of the 16th century, mainly from the Upper Guinea and Kongo-Angola regions. But, the majority (,80%) of the slaves was brought during the 18th and 19th centuries, where Guinea Bissau and Angola were the major sources of slaves. Towards the end of the slave trade, Mozambique contributed significantly as well as Bight of Benin (mainly US import). The current genetic variation of Brazilian populations reflects these geographical and historical sources: Angola and Gabon/Equatorial Guinea (32% and 13%, respectively) represent the majority of Brazilian ancestry, followed by the Senegambia/ PLoS ONE | www.plosone.org 6 January 2011 | Volume 6 | Issue 1 | e14495