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.     

Population genetic analysis of the genes APOE, APOB(3'VNTR) and ACE in some black and Amerindian communities from Colombia

A population genetic study was carried out with the APOE, APOB and ACE loci in 17 Colombian human populations. Ten of them were Amerindian communities coming from the northeastern part of Colombia, Pacific region, Eastern Plains and Amazonia. Six were black populations from Providence Island, Caribbean and Pacific coasts. Finally, the Mestizo population of Bogota was studied as well. The APOE and ACE loci were in Hardy-Weinberg equilibrium, whereas the APOB locus was not studied in all populations. The genetic heterogeneity was substantially greater among the Amerindian populations (G(ST) = 0.059) than in the Afrocolombian populations (G(ST) = 0.009). Also the gene flow population pair estimates were so much higher among the Afrocolombian populations (Nm = 49.08 +/- 43.07) than among Amerindian populations (Nm = 9.66 +/- 18.04). Different phylogenetic and multivariant analyses showed that the Amerindian populations analyzed were clustered in three different arrays: one constituted by the Colombian northeastern and Pacific populations, the second one by the two Amazon populations (Coreguaje and Nukak) and the last one by the Yuco (the unique Caribbe-speaking population among those studied). The latter population was highly divergent from a genetic point of view from the remainder Amerindian populations studied. By using the Mantel test, the existence of a positive and significant correlation between the genetic and geographical distances found among Amerindian populations was demonstrated. This fact was not observed among the Afrocolombian populations. Nevertheless, an isolation-by-distance Slatkin analysis test did not show a significant clear structure of this special pattern among the Indian tribes studied.     

Sex differences in humeral bilateral asymmetry in two hunter‐gatherer populations: California Amerinds and British Columbian Amerinds

This study uses two prehistoric Amerindian populations of hunter‐gatherer subsistence patterns to determine whether levels of sexual dimorphism in humeral bilateral cross‐sectional asymmetry are related to sex‐specific differences in activities among these populations. Results confirmed that males of the California Amerind population who engaged in the more unimanual activities of spear hunting and warfare were more asymmetrical than were their female counterparts who engaged in the more bimanual activities of grinding acorns. California Amerind males were also more asymmetrical than British Columbian Amerind males who rowed (using both arms) extensively. Sex differences within British Columbian Amerinds were not statistically significant, nor were female differences between populations. In general, levels of humeral asymmetry appear to be more dependent on sex and population‐specific behaviors rather than broad subsistence patterns. Am J Phys Anthropol 2009. © 2009 Wiley‐Liss, Inc.     

Analysis of paternal lineages in Brazilian and African populations

The present-day Brazilian population is a consequence of the admixture of various peoples of very different origins, namely, Amerindians, Europeans and Africans. The proportion of each genetic contribution is known to be very heterogeneous throughout the country. The aim of the present study was to compare the male lineages present in two distinct Brazilian populations, as well as to evaluate the African contribution to their male genetic substrate. Thus, two Brazilian population samples from Manaus (State of Amazon) and Ribeirão Preto (State of São Paulo) and three African samples from Guinea Bissau, Angola and Mozambique were typed for a set of nine Y chromosome specific STRs. The data were compared with those from African, Amerindian and European populations. By using Y-STR haplotype information, low genetic distances were found between the Manaus and Ribeirão Preto populations, as well as between these and others from Iberia. Likewise, no significant distances were observed between any of the African samples from Angola, Mozambique and Guinea Bissau. Highly significant Rst values were found between both Brazilian samples and all the African and Amerindian populations. The absence of a significant Sub-Saharan African male component resulting from the slave trade, and the low frequency in Amerindian ancestry Y-lineages in the Manaus and Ribeirão Preto population samples are in accordance with the accentuated gender asymmetry in admixture processes that has been systematically reported in colonial South American populations.     

X‐chromosome lineages and the settlement of the Americas

Most genetic studies on the origins of Native Americans have examined data from mtDNA and Y‐chromosome DNA. To complement these studies and to broaden our understanding of the origin of Native American populations, we present an analysis of 1,873 X‐chromosomes representing Native American (n = 438) and other continental populations (n = 1,435). We genotyped 36 polymorphic sites, forming an informative haplotype within an 8‐kb DNA segment spanning exon 44 of the dystrophin gene. The data reveal continuity from a common Eurasian ancestry between Europeans, Siberians, and Native Americans. However, the loss of two haplotypes frequent in Eurasia (18.8 and 7%) and the rise in frequency of a third haplotype rare elsewhere, indicate a major population bottleneck in the peopling of the Americas. Although genetic drift appears to have played a greater role in the genetic differentiation of Native Americans than in the latitudinally distributed Eurasians, we also observe a signal of a differentiated ancestry of southern and northern populations that cannot be simply explained by the serial southward dilution of genetic diversity. It is possible that the distribution of X‐chromosome lineages reflects the genetic structure of the population of Beringia, itself issued from founder effects and a source of subsequent southern colonization(s). Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.     

HLA polymorphism and evaluation of European, African, and Amerindian contribution to the white and mulatto populations from Paraná, Brazil

Polymorphism of classical HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ genes differs greatly among populations, both in frequencies and in the presence of alleles and haplotypes particular to population groups, making these genes powerful tools for the study of origins of populations and their degree of admixture. Antigen, allele, and haplotype frequencies, together with linkage disequilibrium patterns, are reported for 2 populations in the southern Brazilian state of Paraná, one of predominantly European ancestry (white), the other of predominantly African and European ancestry (mulatto). Genetic distance estimates between the 2 groups and other populations studied previously, and of degree of admixture, were performed. In accordance with phenotypic classification, the white population is of predominantly European origin (80.6%), with a smaller contribution of African (12.5%) and Amerindian (7.0%) genes. The mulatto population consists of African (49.5%) and European (41.8%) ancestry, with a smaller but significant contribution of Amerindian (8.7%) ancestry. On the basis of history and population genetics, there is controversy regarding the Amerindian contribution to Paraná's gene pool. These results provide a better picture of Paraná's ethnic constitution and on the Amerindian contribution to the white and mulatto populations.     

Association of PPARG2 Pro12Ala variant with larger body mass index in Mestizo and Amerindian populations of Mexico

Previous studies have sought to associate the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma2 (PPARG2) gene with type 2 diabetes, insulin resistance, and obesity, with controversial results. We have determined the Pro12Ala variant frequency in 370 nondiabetic Mexican Mestizo subjects and in five Mexican Amerindian groups and have investigated its possible association with lipid metabolism, insulin serum levels, and obesity in three of these populations. Two independent case-control studies were conducted in 239 nondiabetic individuals: 135 case subjects (BMI > or = 25 kg/m2) and 104 control subjects (BMI < 25 kg/m2). The PPARG2 Ala12 allele frequency was higher in most Amerindian populations (0.17 in Yaquis, 0.16 in Mazahuas, 0.16 in Mayans, and 0.20 in Triquis) than in Asians, African Americans, and Caucasians. The Pro12Ala and Ala12Ala (X12Ala) genotypes were significantly associated with greater BMI in Mexican Mestizos and in two Amerindian groups. X12Ala individuals had a higher risk of overweight or obesity than noncarriers in Mestizos (OR = 3.67; 95% CI, 1.42-9.48; p = 0.007) and in Yaquis plus Mazahuas (OR = 3.21; 95% CI, 1.27-8.11; p = 0.013). Our results provide further support of the association between the PPARG2 Ala12 allele and risk of overweight or obesity in Mestizos and two Amerindian populations from Mexico.     

Argentine population genetic structure: large variance in Amerindian contribution

Argentine population genetic structure was examined using a set of 78 ancestry informative markers (AIMs) to assess the contributions of European, Amerindian, and African ancestry in 94 individuals members of this population. Using the Bayesian clustering algorithm STRUCTURE, the mean European contribution was 78%, the Amerindian contribution was 19.4%, and the African contribution was 2.5%. Similar results were found using weighted least mean square method: European, 80.2%; Amerindian, 18.1%; and African, 1.7%. Consistent with previous studies the current results showed very few individuals (four of 94) with greater than 10% African admixture. Notably, when individual admixture was examined, the Amerindian and European admixture showed a very large variance and individual Amerindian contribution ranged from 1.5 to 84.5% in the 94 individual Argentine subjects. These results indicate that admixture must be considered when clinical epidemiology or case control genetic analyses are studied in this population. Moreover, the current study provides a set of informative SNPs that can be used to ascertain or control for this potentially hidden stratification. In addition, the large variance in admixture proportions in individual Argentine subjects shown by this study suggests that this population is appropriate for future admixture mapping studies.     

KIR Gene Content in Amerindians Indicates Influence of Demographic Factors

Although the KIR gene content polymorphism has been studied worldwide, only a few isolated or Amerindian populations have been analyzed. This extremely diverse gene family codifies receptors that are expressed mainly in NK cells and bind HLA class I molecules. KIR-HLA combinations have been associated to several diseases and population studies are important to comprehend their evolution and their role in immunity. Here we analyzed, by PCR-SSP (specific sequencing priming), 327 individuals from four isolated groups of two of the most important Brazilian Amerindian populations: Kaingang and Guarani. The pattern of KIR diversity among these and other ten Amerindian populations disclosed a wide range of variation for both KIR haplotypes and gene frequencies, indicating that demographic factors, such as bottleneck and founder effects, were the most important evolutionary factors in shaping the KIR polymorphism in these populations.     

Analysis of ancient DNA from a prehistoric Amerindian cemetery

The Norris Farms No. 36 cemetery in central Illinois has been the subject of considerable archaeological and genetic research. Both mitochondrial DNA (mtDNA) and nuclear DNA have been examined in this 700-year-old population. DNA preservation at the site was good, with about 70% of the samples producing mtDNA results and approximately 15% yielding nuclear DNA data. All four of the major Amerindian mtDNA haplogroups were found, in addition to a fifth haplogroup. Sequences of the first hypervariable region of the mtDNA control region revealed a high level of diversity in the Norris Farms population and confirmed that the fifth haplogroup associates with Mongolian sequences and hence is probably authentic. Other than a possible reduction in the number of rare mtDNA lineages in many populations, it does not appear as if European contact significantly altered patterns of Amerindian mtDNA variation, despite the large decrease in population size that occurred. For nuclear DNA analysis, a novel method for DNA-based sex identification that uses nucleotide differences between the X and Y copies of the amelogenin gene was developed and applied successfully in approximately 20 individuals. Despite the well-known problems of poor DNA preservation and the ever-present possibility of contamination with modern DNA, genetic analysis of the Norris Farms No. 36 population demonstrates that ancient DNA can be a fruitful source of new insights into prehistoric populations.     

Molecular characterization of mitochondrial Amerindian haplogroups and the amelogenin gene in human ancient DNA from three archaeological sites in Lambayeque - Peru

Important pre-Inca civilizations, known by their great political and religious structures, inhabited the northern coast of Peru. Archeological and anthropological studies have shown that people from these villages have hierarchical strata, but the genetic structure has been poorly studied. Here, we aimed to perform a molecular characterization of the Amerindian maternal lineages and the amelogenin gene in skeletons collected from three archeological sites in Lambayeque. Ancient DNA (aDNA) samples were analyzed with conventional PCR to assess the nine-base pair (9 bp) deletion corresponding to mitochondrial haplogroup B and the identification of haplogroups A, C, and D were obtained with PCR-RFLP experiments. The sex was characterized via amplification of the AMEL(X/Y) locus. Haplogroup frequencies were compared with available data from other ancient and modern civilizations from the Peruvian coast and highlands using statistical methods. Our results showed that haplogroup C had the highest frequency, while haplogroup B showed variable diversity in the analyzed populations. The meta-analysis revealed a positive correlation among some coastal villages. We concluded that ancient populations analyzed in our study showed the presence of four Amerindian mitochondrial haplogroups, which is consistent with previous studies.     

Cytochrome P4501A1 polymorphisms in the Amerindian and Mestizo populations of Mexico

Several polymorphisms in the CYP1A1 locus have been identified and their genotypes appear to exhibit population frequencies that depend on ethnicity. We studied two CYP1A1 polymorphic sites (position 4889 and 6235) in a group of 212 unrelated healthy individuals belonging to three different Mexican populations (106 Mexican Mestizos, 52 Teenek and 54 Mayos). Comparison among Mexican populations showed increased frequency of the *Ile allele (A on position 4889) in Mexican Mestizos when compared to Amerindians (p < 0.05). The analysis of position 6235 showed increased frequencies of *m2 (C in this position) allele in Teenek when compared to Mestizos and Mayos (p < 0.05) and of *m2/*m2 genotype when compared to Mestizos (p < 0.05). Amerindian populations (from Mexico and South America) presented the lowest frequencies of *Ile (position 4889) and *m1 (position 6235) alleles, however these frequencies vary according to the ethnic group studied. Mexican Amerindian groups together with other South Amerindian populations showed the highest frequencies for *Val at position 4889 and the *m2 allele at position 6235. The present study corroborates the high frequencies of*Val and *m2 alleles in the Amerindian populations and detects some differences between Mexican populations that correlate with linguistic differences. Our data could be helpful in understanding the distribution of these polymorphisms and in clarifying their roles as genetic and evolution markers in Amerindian populations.     

Terena Amerindian group autosomal STR data: comparison studies with other Brazilian populations

Allele frequencies for the high polymorphic short tandem repeats (STR) loci PentaE, PentaD, D18S51, D21S11, TH01, D3S1358, FGA, D16S539, D7820, D13S317, vWA and D81179 were analysed in an native Amerindian population from Mato Grosso do Sul state named Terena. Deviations from Hardy–Weinberg expectations were evaluated and the results showed no differences from equilibrium in all loci. The combined power of discrimination and the combined power of exclusion for the 12 tested STR loci were 0.99999999 and 0.999999 respectively. The Terena population data were compared to other from 11 Brazilian populations (Amazônia, Pernambuco, Mato Grosso do Sul, São Paulo, Rio Grande do Sul, Alagoas, Sergipe, Rio Grande do Norte, Santa Catarina, Rondônia and Rio de Janeiro) representing the major Brazilian geographic regions. The F_ST comparative analysis showed no significant differences between all those populations except when comparing Terena with the remained ones.     

Population analysis of vitamin D receptor polymorphisms and the role of genetic ancestry in an admixed population

The vitamin D receptor (VDR) is an essential protein related to bone metabolism. Some VDR alleles are differentially distributed among ethnic populations and display variable patterns of linkage disequilibrium (LD). In this study, 200 unrelated Brazilians were genotyped using 21 VDR single nucleotide polymorphisms (SNPs) and 28 ancestry informative markers. The patterns of LD and haplotype distribution were compared among Brazilian and the HapMap populations of African (YRI), European (CEU) and Asian (JPT+CHB) origins. Conditional regression and haplotype-specific analysis were performed using estimates of individual genetic ancestry in Brazilians as a quantitative trait. Similar patterns of LD were observed in the 5' and 3' gene regions. However, the frequency distribution of haplotype blocks varied among populations. Conditional regression analysis identified haplotypes associated with European and Amerindian ancestry, but not with the proportion of African ancestry. Individual ancestry estimates were associated with VDR haplotypes. These findings reinforce the need to correct for population stratification when performing genetic association studies in admixed populations.     

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.     

Genomic conflict drives patterns of X‐linked population structure in Drosophila neotestacea

Intragenomic conflict has the potential to cause widespread changes in patterns of genetic diversity and genome evolution. In this study, we investigate the consequences of sex‐ratio (SR) drive on the population genetic patterns of the X‐chromosome in Drosophila neotestacea. An SR X‐chromosome prevents the maturation of Y‐bearing sperm during male spermatogenesis and thus is transmitted to ~100% of the offspring, nearly all of which are daughters. Selection on the rest of the genome to suppress SR can be strong, and the resulting conflict over the offspring sex ratio can result in the accumulation of multiple loci on the X‐chromosome that are necessary for the expression of drive. We surveyed variation at 12 random X‐linked microsatellites across 16 populations of D. neotestacea that range in SR frequency from 0% to 30%. First, every locus was differentiated between SR and wild‐type chromosomes, and this drives genetic structure at the X‐chromosome. Once the association with SR is accounted for, the patterns of differentiation among populations are similar to the autosomes. Second, within wild‐type chromosomes, the relative heterozygosity is reduced in populations with an increased prevalence of drive, and the heterozygosity of SR chromosomes is higher than expected based on its prevalence. The combination of the relatively high prevalence of SR drive and the structuring of polymorphism between the SR and wild‐type chromosomes suggests that genetic conflict because of SR drive has had significant consequences on the patterns of X‐linked polymorphism and thus also probably affects the tempo of X‐chromosome evolution in D. neotestacea.     

Inversion polymorphism and a new polytene chromosome map of <Emphasis Type="Italic">Zaprionus indianus</Emphasis> Gupta (1970) (Diptera: drosophilidae)

Zaprionus indianus is a recent invader in Brazil and was probably introduced from the West Afrotropical zone. So far, studies regarding its chromosomal polymorphism were limited to India. We found that Brazilian populations were very different from Indian ones. Five new inversions have been discovered. In(II)A, already described in India, where it is quite common, has also been found in Brazil, where it is very rare. The X-chromosome has three inversions; In(X)Na, In(X)Ke and In(X)Eg, which are frequent in all Brazilian populations studied. In every case, we observed strong linkage disequilibrium among these gene arrangements. During the primary collection period (2001–2002), we noticed a significant positive correlation between the frequency of these inversions and latitude, but this was not confirmed in later investigations. Rearrangement In(IV)EF was also common in all populations, while inversion In(V)B was only found in southern populations. Our data suggest that the founders that recently invaded Brazil were polymorphic for the six inversions observed. The place of origin might be identified more precisely by investigating West African populations. In order to facilitate further investigations, we present an updated polytene chromosome photomap, locating the breakpoints of every inversion observed in Brazilian populations. Galina Ananina and Cláudia Rohde contributed equally to this work     

Brief communication: Population data support the adaptive nature of HACNS1 sapiens/neandertal‐chimpanzee differences in a limb expression domain

The 546‐base pair enhancer of limb expression HACNS1, which is highly constrained in all terrestrial vertebrates, has accumulated 16 human‐specific changes after the human‐chimpanzee split. There has been discussion whether this process was driven by positive selection or biased gene conversion, without considering population data. We studied 83 South Amerindian, 11 Eskimo, 35 Europeans, 37 Bantu, and non‐Bantu Sub‐Saharan speakers, and 28 Brazilian mestizo samples and found no variation in this DNA region. Similar lack of variability in this region was found in four Africans, five Europeans or Euro‐derived, two Asians, one Paleo‐Eskimo, and one Neandertal sequence, whose whole genomes are publicly available. No difference was found. This result favors the interpretation of past positive and present conservative selection, as would expected in a region which influences Homo‐specific traits as important as opposable thumbs, manual dexterity, and bipedal walking. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc.     

Within‐population Y‐linked genetic variation for lifespan in Drosophila melanogaster

The view that the Y chromosome is of little importance for phenotypic evolution stems from early studies of Drosophila melanogaster. This species’ Y chromosome contains only 13 protein‐coding genes, is almost entirely heterochromatic and is not necessary for male viability. Population genetic theory further suggests that non‐neutral variation can only be maintained at the Y chromosome under special circumstances. Yet, recent studies suggest that the D. melanogaster Y chromosome trans‐regulates hundreds to thousands of X and autosomal genes. This finding suggests that the Y chromosome may play a far more active role in adaptive evolution than has previously been assumed. To evaluate the potential for the Y chromosome to contribute to phenotypic evolution from standing genetic variation, we test for Y‐linked variation in lifespan within a population of D. melanogaster. Assessing variation for lifespan provides a powerful test because lifespan (i) shows sexual dimorphism, which the Y is primarily predicted to contribute to, (ii) is influenced by many genes, which provides the Y with many potential regulatory targets and (iii) is sensitive to heterochromatin remodelling, a mechanism through which the Y chromosome is believed to regulate gene expression. Our results show a small but significant effect of the Y chromosome and thus suggest that the Y chromosome has the potential to respond to selection from standing genetic variation. Despite its small effect size, Y‐linked variation may still be important, in particular when evolution of sexual dimorphism is genetically constrained elsewhere in the genome.     

EFFECTIVE POPULATION SIZE AND THE FASTER‐X EFFECT: EMPIRICAL RESULTS AND THEIR INTERPRETATION

The X or Z chromosome has several characteristics that distinguish it from the autosomes, namely hemizygosity in the heterogametic sex, and a potentially different effective population size, both of which may influence the rate and nature of evolution. In particular, there may be an accelerated rate of adaptive change for X‐linked compared to autosomal coding sequences, often referred to as the Faster‐X effect. Empirical studies have indicated that the strength of Faster‐X evolution varies among different species, and theoretical treatments have shown that demography and mating system can substantially affect the degree of Faster‐X evolution. Here we integrate genomic data on Faster‐X evolution from a variety of animals with the demographic factors, mating system, and sex chromosome regulatory characteristics that may influence it. Our results suggest that differences in effective population size and mechanisms of dosage compensation may influence the perceived extent of Faster‐X evolution, and help to explain several clade‐specific patterns that we observe.