The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.

We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10−8) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion.

We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.

Twenty-two years ago, Greenberg, Turner and Zegura (Curr. Anthropol. 27,477-495, 1986) suggested a multidisciplinary model for the human settlement of the New World. Since their synthesis, several studies based mainly on partial evidence such as skull morphology and molecular genetics have presented competing, apparently mutually exclusive, settlement hypotheses. These contradictory views are represented by the genetic-based Single Wave or Out of Beringia models and the cranial morphology-based Two Components/Stocks model. Here, we present a geometric morphometric analysis of 576 late Pleistocene/early Holocene and modern skulls suggesting that the classical Paleoamerican and Mongoloid craniofacial patterns should be viewed as extremes of a continuous morphological variation. Our results also suggest that recent contact among Asian and American circumarctic populations took place during the Holocene. These results along with data from other fields are synthesized in a model for the settlement of the New World that considers, in an integrative and parsimonious way, evidence coming from genetics and physical anthropology. This model takes into account a founder population occupying Beringia during the last glaciation characterized by high craniofacial diversity, founder mtDNA and Y-chromosome lineages and some private autosomal alleles. After a Beringian population expansion, which could have occurred concomitant with their entry into America, more recent circumarctic gene flow would have enabled the dispersion of northeast Asian-derived characters and some particular genetic lineages from East Asia to America and vice versa.