Genomic Data Reveal a Complex Making of Humans

Latin America provides an advantageous setting in which to examine the impact of genetic variation on physical appearance. The region has a history of extensive admixture between three continental populations: Africans, Europeans and Native Americans [5], [6]. Latin America also provides an informative context in which to explore the perception of variation in physical appearance. The region has a unique history relating to the social and cultural politics of ethnicity, race and nation [7]–[9]. A considerable number of genetic studies have examined admixture in Latin America [10]–[14]. However, these analyses have mostly been based on relatively small samples and focused mainly on describing patterns of variation in admixture proportions between individuals and countries/regions. Few studies have examined the impact of genetic ancestry on physical appearance or the relationship of these to individual notions of ethnicity and ancestry [15], [16].

In this paper we present the first phase of a research program focused on the genetics of physical appearance in Latin Americans. We base this program on a sample of over 7,000 individuals ascertained in five countries: Brazil, Chile, Colombia, México and Perú. Information was obtained for a range of socio-demographic variables, physical attributes and self-perception of ancestry. Here we report analyses based on individual mean genome admixture proportions. Coordinate-based spatial analyses illustrate the significant variation in ancestry existing across Latin America, in agreement with demographic history and census information. Significant effects of ancestry were detected for most of the phenotypes examined, and the direction of these effects agrees with the phenotypic differentiation of Africans, Europeans and Native Americans. Finally, we observe that certain phenotypes have a strong impact on self-perception and that these phenotypes bias self-perceived relative to genetically estimated ancestry.


Table 1. Sample size, proportion of women, age, estimated admixture proportions and phenotypic features of the study sample.

Geographic variation of ancestry

Consistent with previous studies, we observe extensive variation in ancestry between countries (Table 1) as well as between individuals within countries (Text S1) and between socioeconomic strata (Text S2) [12], [13], [20]–[22]. In order to obtain a spatial representation of variation in ancestry we obtained interpolated maps based on the geographic coordinates for the birthplaces of research volunteers. The geographic distribution of these birthplaces (Figure 1 and Figure S4) overlaps with regional population density from national census data (Figure S5). Consistent with this pattern, the number of volunteers for each birthplace correlates with census size for these localities: Brazil (r = 0.32, p-value <10−5), Chile (r = 0.51, p-value <10−4), Colombia (r = 0.54, p-value <10−13), Mexico (r = 0.44, p-value <10−8), Perú (r = 0.41, p-value <10−4). Few volunteer birthplaces were thus located in sparsely populated regions (e.g. Amazonia) and geographic interpolation of ancestry in those regions should be regarded with special caution.


Figure 1. Geographic distribution of Native American (blue), African (green) and European (red) ancestry based on individual estimates for samples from (A) Brazil, (B) Chile, (C) Colombia, (D) México and (E) Perú.
To facilitate comparison, color intensity transitions occur at 10% ancestry intervals for all maps. The birthplace of individuals are indicated by purple dots on the African ancestry map. Sampling density is shown in Figure S4. Maps were obtained using Kriging interpolation as detailed in the text.

The Brazilian sample (Figure 1A) shows widespread European ancestry with the highest levels being observed in the south. African ancestry is also widespread (except for the south) and reaches its highest values in the East of the country. Native American ancestry is highest in the north-west (Amazonia). The Chilean sample (Figure 1B) shows the least regional variation, with low levels of African ancestry throughout the country. European and Native American ancestry are relatively uniform, although somewhat higher European ancestry is seen around the main urban areas of the north and centre, Native ancestry predominating elsewhere, particularly in the south. The Colombian sample (Figure 1C) shows highest African ancestry in the coastal regions (particularly on the Pacific) and highest European ancestry in central areas. Native ancestry appears highest in the south-west and in the east of the country (Amazonia) but interpolations in these areas are based on few data points. In the Mexican sample (Figure 1D) Native American ancestry is highest in the centre/south of the country with the north showing the highest proportion of European Ancestry. African ancestry is generally low across Mexico except for a few coastal regions. The Peruvian sample (Figure 1E) shows substantial Native American ancestry throughout the country, particularly in the south, European ancestry appears highest around northern/central areas. African ancestry in Peru is generally low, except for parts of the northern coast.

Genetic ancestry, phenotypic diversity and self-perception

Four ethno/racial categories (“Black”, “White”, “Native” and “Mixed”) are commonly used across Latin America in national censuses and other population surveys. We contrasted genetic ancestry and skin pigmentation (as measured by the melanin index) across these four self-estimated categories for the countries sampled (Figure 2 and Table S4). Within each country there is a gradient of decreasing European ancestry (and increasing pigmentation) for the “White”, “Mixed” and “Native/Black” categories. Across countries, skin pigmentation is relatively uniform within ethnicity categories, except for “Black”. For “White”, “Native” and “Mixed” the mean melanin index across countries varies within ~2 units, while the range for “Black” is ~25 units. By contrast, genetic ancestry varies greatly between countries for all ethnicity categories. For example, European ancestry varies across countries by about 40% for “White”, “Mixed” and “Native” and about 20% for “Black” (Figure 2; estimates for African and Native American ancestry are shown in Table S4).


Figure 2. Bar plots contrasting skin pigmentation (Melanin Index) to proportion of European genetic ancestry across four self-identified ethno/racial categories in samples from Brazil, Chile, Colombia, México and Perú.
Sample sizes and all estimates of pigmentation and ancestry, are presented in Table S4. In Perú no individual self-identified as “Black”.

Contrasting self-perceived (ranked into five bands at 20% increments) and genetically estimated continental ancestry we observe a moderate, but highly significant, correlation: America: r = 0.48, P<2.2×10−6, Europe: r = 0.48, P<2.2×10−6, Africa: r = 0.32, P<2.2×10−6. However, there is a trend for higher self-perceived Native American and African ancestry to exceed the genetic estimates (Figure 3). Similarly, there is a trend for lower self-perceived Native American and European ancestry to underestimate the genetic ancestry (Figure 3). To explore these trends further we performed a multiple linear regression of the difference between self-perceived and genetically estimated ancestry (i.e. the bias, see Methods), using genetic ancestry and covariates as predictors (Table 3). As expected, we observe that genetic ancestry has a highly significant effect (<2×10−16 for all ancestries) and the negative sign of the regression coefficients reflects the orientation of bias seen in Figure 3. At increasing European genetic ancestry, there is greater underestimation in self-perception (a more negative bias). By contrast, with increasing African genetic ancestry there is less overestimation (less positive bias). For Native American ancestry, there is an overestimation (positive bias) at low levels, and an underestimation at high levels of ancestry (negative bias).

Discussion

Since the late 15th century, the population of what is now called “Latin America” has undergone major demographic changes within the context of a highly diversified physical and social environment [6], [23]. These changes include the occurrence of waves of immigration from various parts of Africa and Europe, the resulting decline of the Native populations most exposed to the immigrants and a variable admixture between these groups. There have also been a number of noticeable population movements in the region. For example, in recent generations there has been an extensive migration to the cities, Latin America now being the most urbanized region of the world (about 80% of its population is currently considered urban) [24]. Three of the countries we sampled (Brazil, Mexico and Colombia) are the most populous in the region and the combined population of the five countries examined here account for ~70% of Latin Americans. Although ours is a convenience sample, the individuals studied show considerable variation in birthplace and for a range of biological and social variables, illustrating the extensive heterogeneity of Latin Americans.

The interpolated ancestry maps obtained (Figure 1) are consistent with other genetic studies [20], [21], [25], [26] and with census information on the distribution of the main ethnicity groups within each country (available at geoftp.ibge.gov.br; www.censo2010.org.mx, . Altogether, these data underline the extensive genetic structure existing within and between Latin American countries. It is possible to relate this genetic heterogeneity to well documented historical factors [6], [23], [27]. Broadly, Native American ancestry is highest in areas that were densely populated in pre-Columbian times (particularly Meso-America and the Andean highlands) as well as in regions that received relatively little non-native immigration and which currently have relatively low population densities (e.g. Amazonia). During the colonial period Africans were brought to Latin America as forced labour mainly to coastal tropical areas, particularly in the Caribbean and Brazil [28]. That country was the main recipient of African slaves in the region (representing about 40% of all African slaves brought to the Americas [29]). Early (mostly male) Iberian immigrants settled across the continent, admixing extensively with Native Americans and Africans [5]. These were followed by further currents of European immigration, including individuals from various parts of Europe (often arriving as a result of governmental initiatives) and resulting in the dense settlement of specific geographic regions (such as the south of Brazil). The larger variance in individual ancestry observed for larger urban centres is consistent with the increasing urbanization of Latin America seen recent generations, the cities absorbing immigrants with diverse genetic backgrounds. Other than demographic history, it is possible that assortative mating has also contributed to shaping population structure across Latin America. The Iberian “Conquest” (i.e. the first century of settlement) was characterized by extensive admixture between Natives and immigrants (driven by the highly predominant immigration of males) [5]. However, during the subsequent colonial period society became increasingly stratified, including the instauration during the 18th century of a caste system regulating marriages [6], [27]. These restrictions were mostly abolished with the establishment of republican governments in the 19th century [6]. However, a number of studies have documented continuing assortative mating in Latin America, in relation to genetic ancestry, physical appearance and a range of social factors [30]–[34].

The pattern of variation we observe between physical appearance and genetic ancestry is consistent with information on the variation in frequency of the traits examined in Native Americans, Europeans and Africans. Constitutive skin pigmentation (i.e. in areas not exposed to light), hair and eye color and hair type are traits with little environmental sensitivity and show large differences between continental populations [35]. As expected, increased European ancestry shows a highly significant association with lighter skin, hair and eye pigmentation. A number of allelic variants impacting on these traits have been identified in Europeans and certain of these show large allele frequency differences between Europeans and non-Europeans [1], [2], [36]. We also found a highly significant effect of ancestry on hair type, individuals with higher Native American ancestry showing greater frequency of straight hair, a phenotype that is essentially fixed in Native Americans. Recent studies in East Asians implicate a p.Val370Ala substitution in the EDAR gene in hair morphology [37]–[39]. One of the ancestry informative markers typed here (rs260690) is located in the first intron of EDAR, is in high linkage disequilibrium with the p.Val370Ala variant in the HapMap dataset and is strongly associated with hair type in our sample, after accounting for ancestry (Text S4), suggesting that variants at EDAR could be impacting on hair morphology in Latin Americans. Greater European ancestry also correlates significantly with higher rates of male balding and (marginally) with hair greying (our sample is perhaps underpowered to detect these effects due to its relatively young age; Table 1). Although no thorough comparative data is available, classical population studies indicate that hair greying and androgenetic alopecia are rarer, less severe and of later onset in Native Americans than in other continental populations [40] and our data points to the existence of loci influencing the continental distribution of these traits. Studies in Europeans have recently identified loci associated with androgenetic alopecia [41], [42], but no similar analyses have been performed for hair greying.

Recent genome-wide association analyses in Europeans have implicated loci for variation in height and related anthropometric traits [43], [44]. However, these traits are also strongly influenced by environmental factors, including nutrition [45]. In the sample studied here we find that Native American ancestry correlates significantly with lower height and we also detect a significant effect of socioeconomic position (Text S3), lower socioeconomic position correlating with decreased height. The significant effect of age on height, with younger individuals tending to be taller than older ones suggests that the two socioeconomic indicators examined here (education and wealth) capture only part of the environmental variation impacting on height. The rate of increase in height for individuals born more recently (~0.1 cm/year) estimated here is similar to that obtained from extensive longitudinal surveys in Latin America (~1 cm per decade in the last century), an observation that has been interpreted as resulting from the historical improvement in living standards across the region [45], [46]. It is thus possible that the ancestry effect on height that we detect could be influenced by environmental factors that correlate with ancestry that are not captured by the socioeconomic variables examined here.

The ancestry effects that we detect for facial features (eye fold, face shape and size), but not for head circumference, agree with the notion of a greater developmental and evolutionary constraint on neuro-cranium than on facial variation. This is also in line with proposals that human facial features include a range of environmental adaptations [47]–[49]. Aspects of face shape variation captured by principal components analysis that are influenced by genetic ancestry include mainly, width and height of the face, facial flatness, position of the glabella and fronto-temporal points, extent of eye fold and the relative size and position of lips and nose (a fuller description of face shape variation associated with each PC is presented in Text S5 and Figure S3). Two genome-wide association scans in Europeans have identified a few loci associated with aspects of face shape [50], [51] but these results are pending confirmation by further studies. No genetic variants have yet been implicated in intercontinental differentiation for facial features.

Our joint analysis of genetic, phenotypic and self-perception variation emphasizes the strong impact of physical appearance on self-perception. Comparison of skin pigmentation across self-perceived ethno/racial categories shows remarkable consistency between countries, underlining the weight given to this trait in self-perception [52]. The large variation in genetic ancestry between countries for each ethnicity category illustrates the relatively low predictive power of physical appearance for genetic ancestry. Although we detected highly significant effects of ancestry on many of the phenotypes examined, the observed correlations are relatively low (Table 2). The poor reliability of physical appearance as an indicator of genetic ancestry likely relates to the impact of environmental variation on some of these traits, and to their specific genetic architecture. Particularly, a few genetic variants could have relatively large phenotypic effects (as documented for pigmentation [2], [36]). The impact of physical appearance on self-perception of ancestry likely relates to admixture in Latin America largely occurring many generations ago and the frequent unavailability of reliable genealogical information. The contrast between self-perceived and genetically estimated admixture proportions confirms the impact of physical appearance on self-perception and shows how certain traits, particularly but not exclusively related to pigmentation, can bias self-perception of ancestry. This biased perception of physical attributes is likely to be influenced by social and individual factors shaping the interpretation of phenotypic variation. The effect of such factors is illustrated by the observation of differences in bias across countries and the positive correlation between wealth and European ancestry (Table 2). An effect of wealth on self-perception of ancestry has also been the subject of study in the sociological literature on Latin America [52].

In conclusion, our study sample illustrates the extensive geographic variation in genetic ancestry seen across Latin America, reflecting the heterogeneous demographic history of the region. The highly significant impact of genetic ancestry on physical appearance is consistent with some of the phenotypic variation seen in Latin Americans stemming from genetic loci with differentiated allele frequencies between Africans, Europeans and Native Americans [53]. Further analysis of the study sample collected here should enable the identification of such loci. The significant correlation between self-perceived and genetically estimated ancestry is consistent with the observed effects of genetic ancestry on physical appearance. However, self-perception is biased, possibly due to non-biological factors affecting the perception of phenotypic variation and to the genetic architecture of physical appearance traits. Our findings exemplify the informativity of Latin America for studies encompassing genetic, phenotypic and sociodemographic information and the interest of a multidisciplinary approach to human diversity studies.

Ruiz-Linares A, Adhikari K, Acuña-Alonzo V, Quinto-Sanchez M, Jaramillo C, et al. (2014) Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals. PLoS Genet 10(9): e1004572. doi:10.1371/journal.pgen.1004572