The Genomic and Cultural Diversity of the Inka Qhapaq Hucha Ceremony in Chile and Argentina.

The South American archaeological record has ample evidence of the socio-cultural dynamism of human populations in the past. This has also been supported through the analysis of ancient genomes, by showing evidence of gene flow across the region. While the extent of these signals is yet to be tested, the growing number of ancient genomes allows for more fine-scaled hypotheses to be evaluated. In this study, we assessed the genetic diversity of individuals associated with the Inka ritual, Qhapaq hucha. As part of this ceremony, one or more individuals were buried with Inka and local-style offerings on mountain summits along the Andes, leaving a very distinctive record. Using paleogenomic tools, we analyzed three individuals: two newly generated genomes from El Plomo Mountain (Chile) and El Toro Mountain (Argentina), and a previously published genome from Argentina (Aconcagua Mountain). Our results reveal a complex demographic scenario with each of the individuals showing different genetic affinities. Furthermore, while two individuals showed genetic similarities with present-day and ancient populations from the southern region of the Inka empire, the third individual may have undertaken long-distance movement. The genetic diversity we observed between individuals from similar cultural contexts supports the highly diverse strategies Inka implemented while incorporating new territories. More broadly, this research contributes to our growing understanding of the population dynamics in the Andes by discussing the implications and temporality of population movements in the region.

Differential distribution of NAT2 polymorphisms and NAT2 acetylator phenotypes among indigenous populations of the Brazilian Amazon.

OBJECTIVES: We report, for the first time, the distribution of four no-function NAT2 single nucleotide polymorphisms and inferred NAT2 acetylator phenotypes in three indigenous groups (Munduruku, Paiter-Suruí, and Yanomami), living in reservation areas in the Brazilian Amazon. METHODS: Two hundred and seventy-six participants from three indigenous groups (92 for each group) were included and genotyped for four NAT2 polymorphisms (rs1801279, rs1801280, rs1799930, and rs1799931) by the TaqMan system. Minor Allele Frequency (MAF) was determined and NAT2 acetylator phenotypes were inferred. RESULTS: NAT2 rs1801279G>A was absent in all cohorts; rs1799930G>A was absent in Yanomami and rare (MAF 0.016) in Munduruku and Paiter-Suruí; MAF of rs1801280T>C ranged five-fold (0.092-0.433), and MAF of rs1799931G>A varied between 0.179 and 0.283, among the three groups. The distribution of NAT2 phenotypes differed significantly across cohorts; the prevalence of the slow acetylator phenotype ranged from 16.3% in Yanomami to 33.3% in Munduruku to 48.9% in Paiter-Suruí. This three-fold range of variation is of major clinical relevance because the NAT2 slow phenotype is associated with higher risk of hepatotoxicity with antituberculosis chemotherapy and high incidence rates of tuberculosis and burden of latent infection among Munduruku, Paiter-Surui, and Yanomami peoples. According to the frequency of the NAT2 slow acetylator phenotype, the estimated number of individuals needed to be genotyped to prevent one additional event of hepatotoxicity range from 31 (Munduruku) to 39 (Paiter-Surui) and to 67 (Yanomami). CONCLUSION: The rs1801279 polymorphism was not found in any of the cohorts, while the MAF of the other polymorphisms showed significant variation between the cohorts. The difference in the prevalence of the NAT2 slow acetylator phenotype, which is linked to isoniazid-induced hepatotoxicity, was observed in the different study cohorts.

The need to diversify genomic studies: Insights from Andean highlanders and Amazonians.

More globally diverse perspectives are needed in genomic studies and precision medicine practices on non-Europeans. Here, we illustrate this by discussing the distribution of clinically actionable genetic variants involved in drug response in Andean highlanders and Amazonians, considering their environment, history, genetic structure, and historical biases in the perception of biological diversity of Native Americans.

Pharmacogenetic variability of tuberculosis biomarkers in native and mestizo Peruvian populations.

In Peru, 29 292 people were diagnosed with tuberculosis in 2022. Although tuberculosis treatments are effective, 3.4%-13% are associated with significant adverse drug reactions, with drug-induced liver injury (DILI) considered the most predominant. Among the first-line antituberculosis drugs, isoniazid is the main drug responsible for the appearance of DILI. In liver, isoniazid (INH) is metabolized by N-acetyltransferase-2 (NAT2) and cytochrome P450 2E1 (CYP2E1). Limited information exists on genetic risk factors associated with the presence of DILI to antituberculosis drugs in Latin America, and even less is known about these factors in the native and mestizo Peruvian population. The aim of this study was to determine the prevalence of NAT2 and CYP2E1 genotypes in native and mestizo population. An analytical cross-sectional analysis was performed using genetic data from mestizo population in Lima and native participants from south of Peru. NAT2 metabolizer was determined as fast, intermediate and slow, and CYP2E1 genotypes were classified as c1/c1, c1/c2 and c2/c2, from molecular tests and bioinformatic analyses. Of the 472 participants, 36 and 6 NAT2 haplotypes were identified in the mestizo and native population, respectively. In mestizo population, the most frequent NAT2*5B and NAT2*7B haplotypes were associated with DILI risk; while in natives, NAT2*5G and NAT2*13A haplotypes were associated with decreased risk of DILI. For CYP2E1, c1/c1 and c1/c2 genotypes are the most frequent in natives and mestizos, respectively. The linkage disequilibrium of NAT2 single nucleotide polymorphisms (SNPs) was estimated, detecting a block between all SNPs natives. In addition, a block between rs1801280 and rs1799929 for NAT2 was detected in mestizos. Despite the limitations of a secondary study, it was possible to report associations between NAT2 and CYP2E alleles with Peruvian native and mestizo by prevalence ratios. The results of this study will help the development of new therapeutic strategies for a Tuberculosis efficient control between populations.

Genomic investigation on genes related to mercury metabolism in Amazonian indigenous populations.

Studies have identified elevated levels of mercury in Amazonian Indigenous individuals, highlighting them as one of the most exposed to risks. In the unique context of the Brazilian Indigenous population, it is crucial to identify genetic variants with clinical significance to better understand vulnerability to mercury and its adverse effects. Currently, there is a lack of research on the broader genomic profile of Indigenous people, particularly those from the Amazon region, concerning mercury contamination. Therefore, the aim of this study was to assess the genomic profile related to the processes of mercury absorption, distribution, metabolism, and excretion in 64 Indigenous individuals from the Brazilian Amazon. We aimed to determine whether these individuals exhibit a higher susceptibility to mercury exposure. Our study identified three high-impact variants (GSTA1 rs1051775, GSTM1 rs1183423000, and rs1241704212), with the latter two showing a higher frequency in the study population compared to global populations. Additionally, we discovered seven new variants with modifier impact and a genomic profile different from the worldwide populations. These genetic variants may predispose the study population to more harmful mercury exposure compared to global populations. As the first study to analyze broader genomics of mercury metabolism pathways in Brazilian Amazonian Amerindians, we emphasize that our research aims to contribute to public policies by utilizing genomic investigation as a method to identify populations with a heightened susceptibility to mercury exposure.

New Y-SNPs in QM3 indigenous populations of Colombia.

In evolutionary studies of human populations based on the Y chromosome, the majority of Native Americans belong to the QM3 lineage. Therefore, to study the history of groups inhabiting northern South America, it is necessary to have a higher resolution of the tree. The objective of this work was to identify new SNPs of the QM3 lineage that would allow the evaluation of the phylogenetic relationships between Andean and Amazonian populations of Colombia. Sequences previously obtained from two Y chromosomes of Amazonian populations were used, from which 13 potential SNPs were selected and typed in 171 Amazonian samples from the Vaupés region and in 60 samples from the Pasto, Nasa, Embera, Arhuaco and Kogüi ethnic groups of the Andean region. In addition, the main SNPs/markers (L56, L54, M346, M848, Z780, CTS11780) defining autochthonous Q lineages were typed, along with others defined by different SNPs/markers as reported in the literature (CTS11357, SA05, Z19319, Z5915, and Z19384). It was found that all the new SNPs are present in the Amazonian samples and only 2 of them are shared with the Embera, Nasa and Pasto, but none with the Kogüi and Arhuaco from the northern Andes, in the Colombian Caribbean. Combining the 13 variants of the present study with 14 previously reported and using TMRCA, a new QM3 tree proposal is generated. This method makes it possible to increase the number of sublineages of QM3 with a higher resolution and to detect differences between the different populations of Vaupés in the Amazon, as in the case of the Kubeos and Pisamiras, the latter of which is in grave danger of extinction. These new sublineages are useful for microevolutionary studies of the Amerindian populations of South America.

Genetic determinants and absence of breast cancer in Xavante Indians in Sangradouro Reserve, Brazil.

Genetic compositions of distinct human populations are different. How genomic variants influence many common and rare genetic diseases is always of great medical and anthropological interest, and understanding of genetic architectures of population groups in relation to diseases can advance our knowledge of medicine. Here, we have studied the genomic architecture of a group of Xavante Indians, an indigenous population in Brazil, and compared them with normal populations from the 1000 Genomes Projects. Principal component analysis (PCA) indicates that the Xavante Indians are genetically distinctive when compared to other ethnic groups. No incidence of breast cancer cases has ever been reported in the population, and polygenic risk analysis indicates extremely low breast cancer risk in this population when compared with germline TCGA (The Cancer Genome Atlas) breast cancer normal control samples. Low germinal mutation burden among this population is also observed. Our findings will help to deepen the understanding of breast cancer and might also provide new approaches to study the disease.

Molecular Epidemiology in Amerindians of the Brazilian Amazon Reveals New Genetic Variants in DNA Repair Genes.

Native American populations from the Brazilian Amazon have a low genetic diversity and a different genetic profile when compared to people from other continents. Despite this, few studies have been conducted in this group, and there is no description of their genetic data in the various currently existent international databases. The characterization of the genomic profile of a population not only has an impact in studies of population genetics, but also helps to advance diagnostic and therapeutic response studies, leading to the optimization of clinical applicability. Genetic variations in DNA repair genes have been associated with the modulation of susceptibility to various pathologies, as well as in their prognosis and therapy. This is the first study to investigate DNA repair genes in Amerindians from the Brazilian Amazon region. We investigated 13 important DNA repair genes in the exome of 63 Native Americans, comparing our results with those found in 5 continental populations, whose data are available in the Genome Aggregation Database. Our results showed that 57 variants already described in literature were differentially distributed in the Amerindian populations in relation to the continental populations, 7 of which have significant clinical relevance. In addition, 9 new variants were described, suggesting that they are unique to these populations. Our study reinforces the understanding that the Amazonian Native American population presents a unique genetic profile, and our findings may collaborate with the creation of public policies that optimize the quality of life of these groups as well as the Brazilian population, which presents a high degree of interethnic mixing with Amerindian groups.

Ancient DNA analysis reveals temporal and geographical patterns of mitochondrial diversity in pre-Hispanic populations from Central Argentina.

OBJECTIVES: The study of the ancient populations of Central Argentina has a crucial importance for our understanding of the evolutionary processes in the Southern Cone of South America, given its geographic position as a crossroads. Therefore, the aim of this study is to evaluate the temporal and geographical patterns of genetic variation among the groups that inhabited the current territory of Córdoba Province during the Middle and Late Holocene. METHODS: We analyzed the mitochondrial haplogroups of 74 individuals and 46 Hypervariable Region I (HVR-I) sequences, both novel and previously reported, from archeological populations of the eastern Plains and western Sierras regions of the province of Córdoba. The HVR-I sequences were also compared with other ancient groups from Argentina and with present-day populations from Central Argentina by pairwise distance analysis and identification of shared haplotypes. RESULTS: Significant differences in haplogroup and haplotype distributions between the two geographical regions were found. Sierras showed genetic affinities with certain ancient populations of Northwestern Argentina, while Plains resembled its neighbors from Santiago del Estero Province and the Pampas region. We did not observe genetic differences among the pre 1200 and post 1200 yBP temporal subsets of individuals defined by the emergence of horticulture, considering both geographical samples jointly. CONCLUSIONS: The observed patterns of geographical heterogeneity could indicate the existence of biologically distinct populations inhabiting the mountainous region and the eastern plains of Córdoba Province in pre-Hispanic times. Maternal lineages analyses support a scenario of local evolution with great temporal depth in Central Argentina, with continuity until the present.

Population structure and forensic genetic analyses in Guarani and Kaingang Amerindian populations from Brazil.

When DNA profile comparisons between a crime scene trace and a reference sample generate correspondence, the match probability has to be estimated, so that evaluation of the strength of the forensic DNA evidence can be made. The random match probability estimations require information on allele frequencies and an adjustment factor, referred to as theta (θ) or Fst, a co-ancestry correction factor for subpopulation effects. The θ value has been standardized for urban and isolated populations, but inconsistencies have been reported when it is specifically calculated for smaller and isolated populations, including Amerindian populations. Notably, attempts to characterize forensic markers of these minor populations have been extensively limited and more conservative estimates of the correction factor may be generated for each of them. Therefore, we estimate allele frequencies of 21 autosomal STR markers used for forensic testing and calculated relevant forensic parameters for the set. In addition, we featured the possible structure of five Brazilian Amerindian populations that have been genetically isolated for centuries so we could obtain the appropriate θ value for them. The sample consisted of 319 individuals: (1) 121 Kaingang, from two communities: Ivaí (KIV=61) and Rio das Cobras (KRC=60); and (2) 198 Guaranis from three communities: Mbya from Rio das Cobras (GRC=51), Guarani Ñandeva (GND=71) and Guarani Kaiowá (GKW=76). Between Guarani populations low (Rst=0.0402, p < 10-4) to high (Rst=0.1557, p < 10-5) differentiation was found. Regarding Guarani and Kaingang populations, intermediate (Rst=0.0590, p < 10-5) to high (Rst=0.1604, p < 10-5) differentiation was found. The two Kaingang populations showed very low differentiation between them (Rst=0.0017, p = 0.27), which justifies the union of both genetic data for forensic databases and calculations. The combined power of discrimination (PD) and the combined power of exclusion (PE) were calculated for each population, demonstrating the usefulness of this set of markers in forensic and kinship analysis regarding these populations. Considering the demographic heterogeneity of Amerindian populations in general, the Fst mean value (0.03) was evaluated regarding 43 different indigenous populations from the Americas, including Guaranis and Kaingangs. This result confirms the adequacy of the standardized θ value for the forensic random match probability estimations involving Amerindian populations.

Native American mitochondrial lineages in admixed populations from Chile: Detecting recent migrations during post-Columbian times using geographically restricted lineages.

OBJECTIVES: To analyze the mitochondrial diversity in three admixed populations and evaluate the historical migration effect of native southern population movement to Santiago (capital of Chile). The intensity of migration was quantified using three mitochondrial lineages restricted to South-Central native groups. METHODS: D-loop sequences were genotyped in 550 unrelated individuals from San Felipe-Los Andes (n = 108), Santiago (n = 217), and Concepción (n = 225). Sequence processing, alignment, and haplogroup inference were carried out, and different genetic structure analyses were performed for haplogroup frequencies and D-loop sequences. RESULTS: The Native lineages B2i2, C1b13, and D1g were the most frequent haplogroups, especially in Santiago (71.8%). Despite the distance, this city showed a high-genetic affinity with southern populations, including Concepción (~500 km distant) and native groups, rather than with those from San Felipe-Los Andes (<100 km distant). In fact, there was a negative correlation between geographical and genetic distance among these cities (r corr = -0.5593, p value = 0.8387). Network analysis revealed shared haplotypes between Santiago, Concepción, and other southern populations. Finally, we found lineages from Concepción acting as ancestral nodes in the northern clade. CONCLUSIONS: Considering the geographic distances from these cities, the results were not consistent with a model of genetic isolation by geographic distance, revealing the effects of a historical migration process from the south to the capital. We also show evidence of possible north-to-south migration during admixture onset in Concepción and in addition, we were able to identify previously unreported mitochondrial diversity in urban populations that became lost in Native groups post-European contact.

Remarkably Low KIR and HLA Diversity in Amerindians Reveals Signatures of Strong Purifying Selection Shaping the Centromeric KIR Region.

The killer-cell immunoglobulin-like receptors (KIR) recognize human leukocyte antigen (HLA) molecules to regulate the cytotoxic and inflammatory responses of natural killer cells. KIR genes are encoded by a rapidly evolving gene family on chromosome 19 and present an unusual variation of presence and absence of genes and high allelic diversity. Although many studies have associated KIR polymorphism with susceptibility to several diseases over the last decades, the high-resolution allele-level haplotypes have only recently started to be described in populations. Here, we use a highly innovative custom next-generation sequencing method that provides a state-of-art characterization of KIR and HLA diversity in 706 individuals from eight unique South American populations: five Amerindian populations from Brazil (three Guarani and two Kaingang); one Amerindian population from Paraguay (Aché); and two urban populations from Southern Brazil (European and Japanese descendants from Curitiba). For the first time, we describe complete high-resolution KIR haplotypes in South American populations, exploring copy number, linkage disequilibrium, and KIR-HLA interactions. We show that all Amerindians analyzed to date exhibit the lowest numbers of KIR-HLA interactions among all described worldwide populations, and that 83-97% of their KIR-HLA interactions rely on a few HLA-C molecules. Using multiple approaches, we found signatures of strong purifying selection on the KIR centromeric region, which codes for the strongest NK cell educator receptors, possibly driven by the limited HLA diversity in these populations. Our study expands the current knowledge of KIR genetic diversity in populations to understand KIR-HLA coevolution and its impact on human health and survival.

Population Histories and Genomic Diversity of South American Natives.

South America is home to one of the most culturally diverse present-day native populations. However, the dispersion pattern, genetic substructure, and demographic complexity within South America are still poorly understood. Based on genome-wide data of 58 native populations, we provide a comprehensive scenario of South American indigenous groups considering the genomic, environmental, and linguistic data. Clear patterns of genetic structure were inferred among the South American natives, presenting at least four primary genetic clusters in the Amazonian and savanna regions and three clusters in the Andes and Pacific coast. We detected a cline of genetic variation along a west-east axis, contradicting a hard Andes-Amazon divide. This longitudinal genetic variation seemed to have been shaped by both serial population bottlenecks and isolation by distance. Results indicated that present-day South American substructures recapitulate ancient macroregional ancestries and western Amazonia groups show genetic evidence of cultural exchanges that led to language replacement in precontact times. Finally, demographic inferences pointed to a higher resilience of the western South American groups regarding population collapses caused by the European invasion and indicated precontact population reductions and demic expansions in South America.

Investigating genetic diversity in admixed populations from Ecuador.

OBJECTIVES: According to demographic history, Ecuador has experienced shifts in its Native American populations caused by European colonization and the African slave trade. The continuous admixture events among Europeans, Native Americans, and Africans occurred differently in each region of the country, producing a stratified population. Thus, the aim of this study was to investigate the level of genetic substructure in the Ecuadorian Mestizo population. MATERIALS AND METHODS: A total of 377 male and 209 female samples were genotyped for two sets of X-chromosomal markers (32 X-Indels and 12 X-STRs). Population analyses performed included Hardy-Weinberg equilibrium tests, LD analysis, PCA, pairwise FST s, and AMOVA. RESULTS: Significant levels of LD were observed between markers separated by distances of less than 1 cM, as well as between markers separated by distances varying from 10.891 to 163.53 cM. Among Ecuadorian regions, Amazonia showed the highest average R2 value. DISCUSSION: When X-chromosomal and autosomal differentiation values were compared, a sex-biased admixture between European men and Native American and African women was revealed, as well as between African men and Native American women. Moreover, a distinct Native American ancestry was discernible in the Amazonian population, in addition to sex-biased gene flow between Amazonia and the Andes and Pacific coast regions. Overall, these results underline the importance of integrating X chromosome information to achieve a more comprehensive view of the genetic and demographic histories of South American admixed populations.

The Chilean socio-ethno-genomic cline.

Studies of the current Chilean population performed using classical genetic markers have established that the Chilean population originated primarily from the admixture of European people, particularly Spaniards, and Amerindians. A socioeconomic-ethno-genetic cline was established soon after the conquest. Spaniards born in Spain or Chile occupied the highest Socioeconomic Strata, while Amerindians belonged to the lowest. The intermediate strata consisted of people with different degrees of ethnic admixture; the larger the European admixture, the higher the Socioeconomic Level. The present study of molecular genomic markers sought to calculate the percentage of Amerindian admixture and revealed a finer distribution of this cline, as well as differences between two Amerindian groups: Aymara and Mapuche. The use of two socioeconomic classifications - Class and Socioeconomic Level - reveals important differences. Furthermore, Self-reported Ethnicity (self-assignment to an ethnic group) and Self-reported Ancestry (self-recognition of Amerindian ancestors) show variations and differing relationships between socioeconomic classifications and genomic Amerindian Admixture. These data constitute a valuable input for the formulation of public healthcare policy and show that the notions of Ethnicity, Socioeconomic Strata and Class should always be a consideration in policy development.

Novel loci and Mapuche genetic ancestry are associated with pubertal growth traits in Chilean boys.

Puberty is a complex developmental process that varies considerably among individuals and populations. Genetic factors explain a large proportion of the variability of several pubertal traits. Recent genome-wide association studies (GWAS) have identified hundreds of variants involved in traits that result from body growth, like adult height. However, they do not capture many genetic loci involved in growth changes over distinct growth phases. Further, such GWAS have been mostly performed in Europeans, but it is unknown how these findings relate to other continental populations. In this study, we analyzed the genetic basis of three pubertal traits; namely, peak height velocity (PV), age at PV (APV) and height at APV (HAPV). We analyzed a cohort of 904 admixed Chilean children and adolescents with European and Mapuche Native American ancestries. Height was measured on roughly a [Formula: see text]month basis from childhood to adolescence between 2006 and 2019. We predict that, in average, HAPV is 4.3 cm higher in European than in Mapuche adolescents (P = 0.042), and APV is 0.73 years later in European compared with Mapuche adolescents (P = 0.023). Further, by performing a GWAS on 774, 433 single-nucleotide polymorphisms, we identified a genetic signal harboring 3 linked variants significantly associated with PV in boys (P [Formula: see text]). This signal has never been associated with growth-related traits.

Inflammatory profiles in Chilean Mapuche and non-Mapuche women with gallstones at risk of developing gallbladder cancer.

Chile has high incidence rates of gallbladder cancer globally, particularly among Amerindian women, who also have a high prevalence of gallstones. We examined differences in inflammatory biomarkers between Mapuche and non-Mapuche women from the Chile Biliary Longitudinal Study, a cohort of women with ultrasound-detected gallstones. We randomly selected 200 Mapuche women frequency matched to non-Mapuche women on age and statin use Inflammatory biomarkers were analyzed using a multiplex assay and linear regression to assess associations of a priori markers (CCL20, CXCL10, IL-6, and IL-8) with ethnicity. Novel biomarkers were analyzed using exploratory factor analysis (EFA) and sufficient dimension reduction (SDR) to identify correlated marker groups, followed by linear regression to examine their association with ethnicity. The mean values of IL-8 were higher in Mapuche than non-Mapuche women (P = 0.04), while CCL20, CXCL10, and IL-6 did not differ significantly by ethnicity. EFA revealed two marker groups associated with ethnicity (P = 0.03 and P < 0.001). SDR analysis confirmed correlation between the biomarkers and ethnicity. We found higher IL-8 levels among Mapuche than non-Mapuche women. Novel inflammatory biomarkers were correlated with ethnicity and should be studied further for their role in gallbladder disease. These findings may elucidate underlying ethnic disparities in gallstones and carcinogenesis among Amerindians.

Allelic frequencies with 23 autosomic STRS in the Aymara population of Peru.

Population data of the Aymara in the province of Puno were established for 23 autosomal STR markers. DNA was obtained from unrelated individuals (n = 190) who reside in three areas of the Floating Islands of Lake Titicaca, residents on the border with Bolivia and residents who are not from the border with Bolivia. The PENTA E marker presented the highest PD (0.9738), PIC (0.8793), and PM (0.7847) values. The combined PD was greater than 0.99999999 and the combined PE was 0.99999994. The largest distance, based on Fst values, was between the Aymara population and the Ashaninca population (0.04022), and the smallest distance was with the populations of Bolivia (0.00136) and Peru (0.00525).

A Y-chromosomal survey of Ecuador's multi-ethnic population reveals new insights into the tri-partite population structure and supports an early Holocene age of the rare Native American founder lineage C3-MPB373.

Ecuador is a multiethnic and pluricultural country with a complex history defined by migration and admixture processes. The present study aims to increase our knowledge on the Ecuadorian Native Amerindian groups and the unique South American Y-chromosome haplogroup C3-MPB373 through the analysis of up to 23 Y-chromosome STRs (Y-STRs) and several Y-SNPs in a sample of 527 Ecuadorians from 7 distinct populations and geographic areas, including Kichwa and non-Kichwa Native Amerindians, Mestizos and Afro-Ecuadorians. Our results reveal the presence of C3-MPB373 both in the Amazonian lowland Kichwa with frequencies up to 28 % and, for the first time, in notable proportions in Kichwa populations from the Ecuadorian highlands. The substantially higher frequencies of C3-MPB373 in the Amazonian lowlands found in Kichwa and Waorani individuals suggest a founder effect in that area. Notably, estimates for the time to the most recent common ancestor (TMRCA) in the range of 7.2-9.0 kya point to an ancient origin of the haplogroup and suggest an early Holocene expansion of C3-MPB373 into South America. Finally, the pairwise genetic distances (RST) separate the Kichwa Salasaka from all the other Native Amerindian and Ecuadorian groups, indicating a so far hidden diversity among the Kichwa-speaking populations and suggesting a more southern origin of this population. In sum, our study provides a more in-depth knowledge of the male genetic structure of the multiethnic Ecuadorian population, as well as a valuable reference dataset for forensic use.

Genetic assessment reveals no population substructure and divergent regional and sex-specific histories in the Chachapoyas from northeast Peru.

Many native populations in South America have been severely impacted by two relatively recent historical events, the Inca and the Spanish conquest. However decisive these disruptive events may have been, the populations and their gene pools have been shaped markedly also by the history prior to the conquests. This study focuses mainly on the Chachapoya peoples that inhabit the montane forests on the eastern slopes of the northern Peruvian Andes, but also includes three distinct neighboring populations (the Jívaro, the Huancas and the Cajamarca). By assessing mitochondrial, Y-chromosomal and autosomal diversity in the region, we explore questions that have emerged from archaeological and historical studies of the regional culture (s). These studies have shown, among others, that Chachapoyas was a crossroads for Coast-Andes-Amazon interactions since very early times. In this study, we examine the following questions: 1) was there pre-Hispanic genetic population substructure in the Chachapoyas sample? 2) did the Spanish conquest cause a more severe population decline on Chachapoyan males than on females? 3) can we detect different patterns of European gene flow in the Chachapoyas region? and, 4) did the demographic history in the Chachapoyas resemble the one from the Andean area? Despite cultural differences within the Chachapoyas region as shown by archaeological and ethnohistorical research, genetic markers show no significant evidence for past or current population substructure, although an Amazonian gene flow dynamic in the northern part of this territory is suggested. The data also indicates a bottleneck c. 25 generations ago that was more severe among males than females, as well as divergent population histories for populations in the Andean and Amazonian regions. In line with previous studies, we observe high genetic diversity in the Chachapoyas, despite the documented dramatic population declines. The diverse topography and great biodiversity of the northeastern Peruvian montane forests are potential contributing agents in shaping and maintaining the high genetic diversity in the Chachapoyas region.