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.

A positively selected FBN1 missense variant reduces height in Peruvian individuals.

On average, Peruvian individuals are among the shortest in the world1. Here we show that Native American ancestry is associated with reduced height in an ethnically diverse group of Peruvian individuals, and identify a population-specific, missense variant in the FBN1 gene (E1297G) that is significantly associated with lower height. Each copy of the minor allele (frequency of 4.7%) reduces height by 2.2 cm (4.4 cm in homozygous individuals). To our knowledge, this is the largest effect size known for a common height-associated variant. FBN1 encodes the extracellular matrix protein fibrillin 1, which is a major structural component of microfibrils. We observed less densely packed fibrillin-1-rich microfibrils with irregular edges in the skin of individuals who were homozygous for G1297 compared with individuals who were homozygous for E1297. Moreover, we show that the E1297G locus is under positive selection in non-African populations, and that the E1297 variant shows subtle evidence of positive selection specifically within the Peruvian population. This variant is also significantly more frequent in coastal Peruvian populations than in populations from the Andes or the Amazon, which suggests that short stature might be the result of adaptation to factors that are associated with the coastal environment in Peru.

Native American gene flow into Polynesia predating Easter Island settlement.

The possibility of voyaging contact between prehistoric Polynesian and Native American populations has long intrigued researchers. Proponents have pointed to the existence of New World crops, such as the sweet potato and bottle gourd, in the Polynesian archaeological record, but nowhere else outside the pre-Columbian Americas1-6, while critics have argued that these botanical dispersals need not have been human mediated7. The Norwegian explorer Thor Heyerdahl controversially suggested that prehistoric South American populations had an important role in the settlement of east Polynesia and particularly of Easter Island (Rapa Nui)2. Several limited molecular genetic studies have reached opposing conclusions, and the possibility continues to be as hotly contested today as it was when first suggested8-12. Here we analyse genome-wide variation in individuals from islands across Polynesia for signs of Native American admixture, analysing 807 individuals from 17 island populations and 15 Pacific coast Native American groups. We find conclusive evidence for prehistoric contact of Polynesian individuals with Native American individuals (around AD 1200) contemporaneous with the settlement of remote Oceania13-15. Our analyses suggest strongly that a single contact event occurred in eastern Polynesia, before the settlement of Rapa Nui, between Polynesian individuals and a Native American group most closely related to the indigenous inhabitants of present-day Colombia.

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.

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.

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.

Genomic insight into the origins and dispersal of the Brazilian coastal natives.

In the 15th century, ∼900,000 Native Americans, mostly Tupí speakers, lived on the Brazilian coast. By the end of the 18th century, the coastal native populations were declared extinct. The Tupí arrived on the east coast after leaving the Amazonian basin ∼2,000 y before present; however, there is no consensus on how this migration occurred: toward the northern Amazon and then directly to the Atlantic coast, or heading south into the continent and then migrating to the coast. Here we leveraged genomic data from one of the last remaining putative representatives of the Tupí coastal branch, a small, admixed, self-reported Tupiniquim community, as well as data of a Guaraní Mbyá native population from Southern Brazil and of three other native populations from the Amazonian region. We demonstrated that the Tupiniquim Native American ancestry is not related to any extant Brazilian Native American population already studied, and thus they could be considered the only living representatives of the extinct Tupí branch that used to settle the Atlantic Coast of Brazil. Furthermore, these data show evidence of a direct migration from Amazon to the Northeast Coast in pre-Columbian time, giving rise to the Tupí Coastal populations, and a single distinct migration southward that originated the Guaraní people from Brazil and Paraguay. This study elucidates the population dynamics and diversification of the Brazilian natives at a genomic level, which was made possible by recovering data from the Brazilian coastal population through the genomes of mestizo individuals.

Integration of ancient DNA with transdisciplinary dataset finds strong support for Inca resettlement in the south Peruvian coast.

Ancient DNA (aDNA) analysis provides a powerful means of investigating human migration, social organization, and a plethora of other crucial questions about humanity's past. Recently, specialists have suggested that the ideal research design involving aDNA would include multiple independent lines of evidence. In this paper, we adopt a transdisciplinary approach integrating aDNA with archaeological, biogeochemical, and historical data to investigate six individuals found in two cemeteries that date to the Late Horizon (1400 to 1532 CE) and Colonial (1532 to 1825 CE) periods in the Chincha Valley of southern Peru. Genomic analyses indicate that these individuals are genetically most similar to ancient and present-day populations from the north Peruvian coast located several hundred kilometers away. These genomic data are consistent with 16th century written records as well as ceramic, textile, and isotopic data. These results provide some of the strongest evidence yet of state-sponsored resettlement in the pre-Colonial Andes. This study highlights the power of transdisciplinary research designs when using aDNA data and sets a methodological standard for investigating ancient mobility in complex societies.

The genetic structure and adaptation of Andean highlanders and Amazonians are influenced by the interplay between geography and culture.

Western South America was one of the worldwide cradles of civilization. The well-known Inca Empire was the tip of the iceberg of an evolutionary process that started 11,000 to 14,000 years ago. Genetic data from 18 Peruvian populations reveal the following: 1) The between-population homogenization of the central southern Andes and its differentiation with respect to Amazonian populations of similar latitudes do not extend northward. Instead, longitudinal gene flow between the northern coast of Peru, Andes, and Amazonia accompanied cultural and socioeconomic interactions revealed by archeology. This pattern recapitulates the environmental and cultural differentiation between the fertile north, where altitudes are lower, and the arid south, where the Andes are higher, acting as a genetic barrier between the sharply different environments of the Andes and Amazonia. 2) The genetic homogenization between the populations of the arid Andes is not only due to migrations during the Inca Empire or the subsequent colonial period. It started at least during the earlier expansion of the Wari Empire (600 to 1,000 years before present). 3) This demographic history allowed for cases of positive natural selection in the high and arid Andes vs. the low Amazon tropical forest: in the Andes, a putative enhancer in HAND2-AS1 (heart and neural crest derivatives expressed 2 antisense RNA1, a noncoding gene related to cardiovascular function) and rs269868-C/Ser1067 in DUOX2 (dual oxidase 2, related to thyroid function and innate immunity) genes and, in the Amazon, the gene encoding for the CD45 protein, essential for antigen recognition by T and B lymphocytes in viral-host interaction.

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.

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.

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).

Genetic evidence for two founding populations of the Americas.

Genetic studies have consistently indicated a single common origin of Native American groups from Central and South America. However, some morphological studies have suggested a more complex picture, whereby the northeast Asian affinities of present-day Native Americans contrast with a distinctive morphology seen in some of the earliest American skeletons, which share traits with present-day Australasians (indigenous groups in Australia, Melanesia, and island Southeast Asia). Here we analyse genome-wide data to show that some Amazonian Native Americans descend partly from a Native American founding population that carried ancestry more closely related to indigenous Australians, New Guineans and Andaman Islanders than to any present-day Eurasians or Native Americans. This signature is not present to the same extent, or at all, in present-day Northern and Central Americans or in a ∼12,600-year-old Clovis-associated genome, suggesting a more diverse set of founding populations of the Americas than previously accepted.

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.

Genomic insights into the origin and diversification of late maritime hunter-gatherers from the Chilean Patagonia.

Patagonia was the last region of the Americas reached by humans who entered the continent from Siberia ∼15,000-20,000 y ago. Despite recent genomic approaches to reconstruct the continental evolutionary history, regional characterization of ancient and modern genomes remains understudied. Exploring the genomic diversity within Patagonia is not just a valuable strategy to gain a better understanding of the history and diversification of human populations in the southernmost tip of the Americas, but it would also improve the representation of Native American diversity in global databases of human variation. Here, we present genome data from four modern populations from Central Southern Chile and Patagonia (n = 61) and four ancient maritime individuals from Patagonia (∼1,000 y old). Both the modern and ancient individuals studied in this work have a greater genetic affinity with other modern Native Americans than to any non-American population, showing within South America a clear structure between major geographical regions. Native Patagonian Kawéskar and Yámana showed the highest genetic affinity with the ancient individuals, indicating genetic continuity in the region during the past 1,000 y before present, together with an important agreement between the ethnic affiliation and historical distribution of both groups. Lastly, the ancient maritime individuals were genetically equidistant to a ∼200-y-old terrestrial hunter-gatherer from Tierra del Fuego, which supports a model with an initial separation of a common ancestral group to both maritime populations from a terrestrial population, with a later diversification of the maritime groups.

Evolutionary genomic dynamics of Peruvians before, during, and after the Inca Empire.

Native Americans from the Amazon, Andes, and coastal geographic regions of South America have a rich cultural heritage but are genetically understudied, therefore leading to gaps in our knowledge of their genomic architecture and demographic history. In this study, we sequence 150 genomes to high coverage combined with an additional 130 genotype array samples from Native American and mestizo populations in Peru. The majority of our samples possess greater than 90% Native American ancestry, which makes this the most extensive Native American sequencing project to date. Demographic modeling reveals that the peopling of Peru began ∼12,000 y ago, consistent with the hypothesis of the rapid peopling of the Americas and Peruvian archeological data. We find that the Native American populations possess distinct ancestral divisions, whereas the mestizo groups were admixtures of multiple Native American communities that occurred before and during the Inca Empire and Spanish rule. In addition, the mestizo communities also show Spanish introgression largely following Peruvian Independence, nearly 300 y after Spain conquered Peru. Further, we estimate migration events between Peruvian populations from all three geographic regions with the majority of between-region migration moving from the high Andes to the low-altitude Amazon and coast. As such, we present a detailed model of the evolutionary dynamics which impacted the genomes of modern-day Peruvians and a Native American ancestry dataset that will serve as a beneficial resource to addressing the underrepresentation of Native American ancestry in sequencing studies.

Tracing the genetic history of the 'Cañaris' from Ecuador and Peru using uniparental DNA markers.

BACKGROUND: According to history, in the pre-Hispanic period, during the conquest and Inka expansion in Ecuador, many Andean families of the Cañar region would have been displaced to several places of Tawantinsuyu, including Kañaris, a Quechua-speaking community located at the highlands of the Province of Ferreñafe, Lambayeque (Peru). Other families were probably taken from the Central Andes to a place close to Kañaris, named Inkawasi. Evidence of this migration comes from the presence near the Kañaris-Inkawasi communities of a village, a former Inka camp, which persists until the present day. This scenario could explain these toponyms, but it is still controversial. To clarify this historical question, the study presented here focused on the inference of the genetic relationship between 'Cañaris' populations, particularly of Cañar and Ferreñafe, compared to other highland populations. We analysed native patrilineal Y chromosome haplotypes composed of 15 short tandem repeats, a set of SNPs, and maternal mitochondrial DNA haplotypes of control region sequences. RESULTS: After the genetic comparisons of local populations-three from Ecuador and seven from Peru-, Y chromosome analyses (n = 376) indicated that individuals from the Cañar region do not share Y haplotypes with the Kañaris, or even with those of the Inkawasi. However, some Y haplotypes of Ecuadorian 'Cañaris' were associated with haplotypes of the Peruvian populations of Cajamarca, Chivay (Arequipa), Cusco and Lake Titicaca, an observation that is congruent with colonial records. Within the Kañaris and Inkawasi communities there are at least five clans in which several individuals share haplotypes, indicating that they have recent common ancestors. Despite their relative isolation, most individuals of both communities are related to those of the Cajamarca and Chachapoyas in Peru, consistent with the spoken Quechua and their geographic proximity. With respect to mitochondrial DNA haplotypes (n = 379), with the exception of a shared haplotype of the D1 lineage between the Cañar and Kañaris, there are no genetic affinities. CONCLUSION: Although there is no close genetic relationship between the Peruvian Kañaris (including Inkawasi) and Ecuadorian Cañar populations, our results showed some congruence with historical records.

Dissecting the Pre-Columbian Genomic Ancestry of Native Americans along the Andes-Amazonia Divide.

Extensive European and African admixture coupled with loss of Amerindian lineages makes the reconstruction of pre-Columbian history of Native Americans based on present-day genomes extremely challenging. Still open questions remain about the dispersals that occurred throughout the continent after the initial peopling from the Beringia, especially concerning the number and dynamics of diffusions into South America. Indeed, if environmental and historical factors contributed to shape distinct gene pools in the Andes and Amazonia, the origins of this East-West genetic structure and the extension of further interactions between populations residing along this divide are still not well understood. To this end, we generated new high-resolution genome-wide data for 229 individuals representative of one Central and ten South Amerindian ethnic groups from Mexico, Peru, Bolivia, and Argentina. Low levels of European and African admixture in the sampled individuals allowed the application of fine-scale haplotype-based methods and demographic modeling approaches. These analyses revealed highly specific Native American genetic ancestries and great intragroup homogeneity, along with limited traces of gene flow mainly from the Andes into Peruvian Amazonians. Substantial amount of genetic drift differentially experienced by the considered populations underlined distinct patterns of recent inbreeding or prolonged isolation. Overall, our results support the hypothesis that all non-Andean South Americans are compatible with descending from a common lineage, while we found low support for common Mesoamerican ancestors of both Andeans and other South American groups. These findings suggest extensive back-migrations into Central America from non-Andean sources or conceal distinct peopling events into the Southern Continent.

Pharmacogenomics of thiopurines: distribution of TPMT and NUDT15 polymorphisms in the Brazilian Amazon.

Reduced function alleles in the TPMT and NUDT15 genes are risk factors for thiopurine toxicity. This study evaluated the influence of Native ancestry on the distribution of TPMT (rs1142345, rs1800460 and rs1800462) and NUDT15 (rs116855232) polymorphisms and compound metabolic phenotypes in 128 healthy males from the Brazilian Amazon. The average proportion of Native and European ancestry differed greatly and significantly between self-declared Amerindians and non-Amerindians, although extensive admixture in both groups was evident. Native ancestry was not significantly associated with the frequency distribution of the TPMT or NUDT15 polymorphisms investigated. The apparent discrepancy with our previous results for NUDT15 rs116855232 in the Ad Mixed American superpopulation of the 1000 Genomes Project is ascribed to the diversity of the Native populations of the Americas. Based on the inferred TPMT/NUDT15 compound metabolic phenotypes, the Clinical Pharmacogenetics Implementation Consortium recommendations for starting thiopurine therapy with reduced doses or to consider dose reduction applied respectively to 3-5% and to 12-20% of the study cohorts.

New Evidence of Ancient Mitochondrial DNA of the Southern Andes (Calchaquí Valleys, Northwest Argentina, 3,600-1,900 Years before Present).

Genetic studies on pre-Hispanic populations of the Southern Andes have been increasing steadily in the last decade. Nevertheless, ancient DNA characterization of Formative Period archaeological human remains is particularly scant, especially for Northwest Argentina. To expand current information on genetic characterization of the first agricultural communities of the southern Calchaquí Valleys, we present and discuss the first mitochondrial ancient DNA information obtained on samples dated to ca. 3,600-1,900 years before present from the Cajón Valley, Catamarca Province. Reproducible mtDNA hypervariable region 1 (HVR-1) sequences were obtained in seven individuals. Mitochondrial HVR-1 haplotypes were assigned to three of the four founding haplogroups, D1 (57.1%), C1 (28.5%), and B2 (14.2%), with absence of A2. Our results show that the Cajón Valley sample, with predominance of D1 and C1, differs from that commonly observed in ancient and modern Andean populations, which usually show a high prevalence of haplogroup B2. The fact that the Cajón Valley and Pampa Grande (Salta Province, Argentina) share a prevalence of haplogroup D1 could provide additional evidence to support possible genetic affinities between the valleys and the eastern sub-Andean region during the Formative Period in Northwest Argentina, expanding the archaeological evidence of contact between both populations. Future complete mitogenomic analysis will provide substantial information to formulate new hypotheses about the origins and phylogenetic relationships between the individuals of the Cajón Valley and other groups from the Andes, Gran Chaco, and the Amazon.