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A valuable approach to understand how individual and population genetic differences can predispose to disease is to assess the impact of genetic variants on cellular functions (e.g., gene expression) of cell and tissue types related to pathological states. To understand the genetic basis of nonsyndromic cleft lip with or without cleft palate (NSCL/P) susceptibility, a complex and highly prevalent congenital malformation, we searched for genetic variants with a regulatory role in a disease-related tissue, the lip muscle (orbicularis oris muscle [OOM]), of affected individuals. From 46 OOM samples, which are frequently discarded during routine corrective surgeries on patients with orofacial clefts, we derived mesenchymal stem cells and correlated the individual genetic variants with gene expression from these cultured cells. Through this strategy, we detected significant cis-eQTLs (i.e., DNA variants affecting gene expression) and selected a few candidates to conduct an association study in a large Brazilian cohort (624 patients and 668 controls). This resulted in the discovery of a novel susceptibility locus for NSCL/P, rs1063588, the best eQTL for the MRPL53 gene, where evidence for association was mostly driven by the Native American ancestry component of our Brazilian sample. MRPL53 (2p13.1) encodes a 39S protein subunit of mitochondrial ribosomes and interacts with MYC, a transcription factor required for normal facial morphogenesis. Our study illustrates not only the importance of sampling admixed populations but also the relevance of measuring the functional effects of genetic variants over gene expression to dissect the complexity of disease phenotypes. [ABSTRACT FROM AUTHOR]

The article presents the study which discusses how genetic information can help determine the composition of an organism more specifically in dogs. It mentions that such animal has a beneficial relationship with humans and that their limited number of genes is the main reason for some of the phenotypic differences between breeds. It relates that they are also ideal subjects in investigating the genetic basis of susceptibility to illnesses.

The COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Although our understanding of the pandemic has improved significantly since the beginning, the natural history of COVID-19 and its impacts on under-represented populations, such as Indigenous people from America, remain largely unknown. We performed a retrospective serological survey with two Brazilian Indigenous populations (n=624), Tupiniquim and Guarani-Mbyá. Samples were collected between September 2020 and July 2021: a period comprising the dissemination of SARS-CoV-2 variants and the beginning of COVID-19 vaccination in Brazil. Seroconversions against S and N antigens were assessed using three different commercially available ELISA kits. Samples were also used to assess the prevalence of tuberculosis (TB) in the same population (n=529). Seroconversion against SARS-CoV-2 antigens was considered positive if at least one of the three ELISA kits detected levels of specific antibodies above the threshold specified by the manufacturer. In this sense, we report 56.0% (n=349/623) of seroconverted individuals. Relative seroconversion peaked after introduction of the Coronavac vaccine in February 2021. Vaccination increased the production of anti-S IgG from 3.9% to 48.6%. Our results also indicated that 11.0% (n=46/417) of all individuals were positive for TB. Seroconversion to SARS-CoV-2 was similar between individuals with positive tuberculosis test results to those with negative test results. Most vaccinated individuals seroconverted to SARS-CoV-2, indicating that Coronavac may be as protective in individuals from these indigenous groups as observed in the general Brazilian population. COVID-19 severity was minimal regardless of incomplete vaccine coverage, suggesting that vaccination may not be the only factor protecting individuals from severe COVID-19. Tuberculosis is highly prevalent and not associated with increased seroconversion to SARS-CoV-2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Nagai, Lemes, Mill, Pereira, Marques and Hünemeier.)

Modern humans originated in Africa 300,000 yr ago, and before leaving their continent of origin, they underwent a process of intense diversification involving complex demographic dynamics. Upon exiting Africa, different populations emerged on the four other inhabited continents, shaped by the interplay of various evolutionary processes, such as migrations, founder effects, and natural selection. Within each region, continental populations, in turn, diversified and evolved almost independently for millennia. As a backdrop to this diversification, introgressions from archaic species contributed to establishing different patterns of genetic diversity in different geographic regions, reshaping our understanding of our species' variability. With the increasing availability of genomic data, it has become possible to delineate the subcontinental human population structure precisely. However, the bias toward the genomic research focused on populations from the global North has limited our understanding of the real diversity of our species and the processes and events that guided different human groups throughout their evolutionary history. This perspective is part of a series of articles celebrating 40 yr since our journal, Molecular Biology and Evolution, was founded (Russo et al. 2024). The perspective is accompanied by virtual issues, a selection of papers on human diversification published by Genome Biology and Evolution and Molecular Biology and Evolution., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

COVID-19 pandemic represented a worldwide major challenge in different areas, and efforts undertaken by the scientific community led to the understanding of some of the genetic determinants that influence the different COVID-19 outcomes. In this paper, we review the studies about the role of human genetics in COVID-19 severity and how Brazilian studies also contributed to those findings. Rare variants in genes related to Inborn Errors of Immunity (IEI) in the type I interferons pathway, and its phenocopies, have been described as being causative of severe outcomes. IEI and its phenocopies are present in Brazil, not only in COVID-19 patients, but also in autoimmune conditions and severe reactions to yellow fever vaccine. In addition, studies focusing on common variants and GWAS studies encompassing worldwide patients have found several loci associated with COVID-19 severity. A GWAS study including only Brazilian COVID-19 patients identified a new locus 1q32.1 associated with COVID-19 severity. Thus, more comprehensive studies considering the Brazilian genomic diversity should be performed, since they can help to reveal not only what are the genetic determinants that contribute to the different outcomes for COVID-19 in the Brazilian population, but in the understanding of human genetics in different health conditions.

The cultural and biological diversity of South American indigenous groups represent extremes of human variability, exhibiting one of the highest linguistic diversities alongside a remarkably low within-population genetic variation and an extremely high inter-population genetic differentiation. On top of that, this region has seen some of the most dramatic demographic events in human history unleashed by the European colonization of the Americas. As a result of this process, the distribution of indigenous populations has been radically changed. In this review we focus on the Tupi, the largest and most widespread linguistic family in eastern South America. Tupi are believed to have originated in southwestern Amazon, from where some of its subfamilies expanded into other parts of the Amazon and, in the case of the Tupi-Guarani, beyond its borders. Recent evidence from archaeology, linguistics, and genetics aligns with José Brochado's Tupi Expansion model. He proposed that the gradual development of agricultural systems within the Amazon resulted in population growth and, eventually, territorial expansion. This model also supports separate Tupi Expansion branches: Tupinambá (Atlantic coast) and Guarani (south, midwest Brazil). Although being the most populous group on Brazil's Atlantic coast, which was the most affected by European colonization, the Tupi still account for roughly 20% of the country's overall indigenous population. Finally, despite its importance and more than a century of research on the Tupi and their expansion history, many key questions remain unanswered, which we attempt to summarize and explore here., (© 2023 The Authors. American Journal of Biological Anthropology published by Wiley Periodicals LLC.)

The Nav1.7 voltage-gated sodium channel plays a key role in nociception. Three functional variants in the SCN9A gene (encoding M932L, V991L, and D1908G in Nav1.7), have recently been identified as stemming from Neanderthal introgression and to associate with pain symptomatology in UK BioBank data. In 1000 genomes data, these variants are absent in Europeans but common in Latin Americans. Analysing high-density genotype data from 7594 Latin Americans, we characterized Neanderthal introgression in SCN9A. We find that tracts of introgression occur on a Native American genomic background, have an average length of ~123 kb and overlap the M932L, V991L, and D1908G coding positions. Furthermore, we measured experimentally six pain thresholds in 1623 healthy Colombians. We found that Neanderthal ancestry in SCN9A is significantly associated with a lower mechanical pain threshold after sensitization with mustard oil and evidence of additivity of effects across Nav1.7 variants. Our findings support the reported association of Neanderthal Nav1.7 variants with clinical pain, define a specific sensory modality affected by archaic introgression in SCN9A and are consistent with independent effects of the Neanderthal variants on Nav1.7 function., (© 2023. Springer Nature Limited.)

Sambaqui (shellmound) societies are among the most intriguing archaeological phenomena in pre-colonial South America, extending from approximately 8,000 to 1,000 years before present (yr BP) across 3,000 km on the Atlantic coast. However, little is known about their connection to early Holocene hunter-gatherers, how this may have contributed to different historical pathways and the processes through which late Holocene ceramists came to rule the coast shortly before European contact. To contribute to our understanding of the population history of indigenous societies on the eastern coast of South America, we produced genome-wide data from 34 ancient individuals as early as 10,000 yr BP from four different regions in Brazil. Early Holocene hunter-gatherers were found to lack shared genetic drift among themselves and with later populations from eastern South America, suggesting that they derived from a common radiation and did not contribute substantially to later coastal groups. Our analyses show genetic heterogeneity among contemporaneous Sambaqui groups from the southeastern and southern Brazilian coast, contrary to the similarity expressed in the archaeological record. The complex history of intercultural contact between inland horticulturists and coastal populations becomes genetically evident during the final horizon of Sambaqui societies, from around 2,200 yr BP, corroborating evidence of cultural change., (© 2023. The Author(s).)

We report a genome-wide association study of facial features in >6000 Latin Americans based on automatic landmarking of 2D portraits and testing for association with inter-landmark distances. We detected significant associations (P-value <5 × 10 -8 ) at 42 genome regions, nine of which have been previously reported. In follow-up analyses, 26 of the 33 novel regions replicate in East Asians, Europeans, or Africans, and one mouse homologous region influences craniofacial morphology in mice. The novel region in 1q32.3 shows introgression from Neanderthals and we find that the introgressed tract increases nasal height (consistent with the differentiation between Neanderthals and modern humans). Novel regions include candidate genes and genome regulatory elements previously implicated in craniofacial development, and show preferential transcription in cranial neural crest cells. The automated approach used here should simplify the collection of large study samples from across the world, facilitating a cosmopolitan characterization of the genetics of facial features., (© 2023. The Author(s).)

Motivation: This work is motivated by the problem of identifying homozygosity islands on the genome of individuals in a population. Our method directly tackles the issue of identification of the homozygosity islands at the population level, without the need of analysing single individuals and then combine the results, as is made nowadays in state-of-the-art approaches., Results: We propose regularized offline change-point methods to detect changes in the parameters of a multidimensional distribution when we have several aligned, independent samples of fixed resolution. We present a penalized maximum likelihood approach that can be efficiently computed by a dynamic programming algorithm or approximated by a fast binary segmentation algorithm. Both estimators are shown to converge almost surely to the set of change-points without the need of specifying a priori the number of change-points. In simulation, we observed similar performances from the exact and greedy estimators. Moreover, we provide a new methodology for the selection of the regularization constant which has the advantage of being automatic, consistent, and less prone to subjective analysis., Availability and Implementation: The data used in the application are from the Human Genome Diversity Project (HGDP) and is publicly available. Algorithms were implemented using the R software R Core Team (R: A Language and Environment for Statistical Computing. Vienna (Austria): R Foundation for Statistical Computing, 2020.) in the R package blockcpd, found at https://github.com/Lucas-Prates/blockcpd., (© The Author(s) 2023. Published by Oxford University Press.)

Ecological conditions in the Amazon rainforests are historically favorable for the transmission of numerous tropical diseases, especially vector-borne diseases. The high diversity of pathogens likely contributes to the strong selective pressures for human survival and reproduction in this region. However, the genetic basis of human adaptation to this complex ecosystem remains unclear. This study investigates the possible footprints of genetic adaptation to the Amazon rainforest environment by analyzing the genomic data of 19 native populations. The results based on genomic and functional analysis showed an intense signal of natural selection in a set of genes related to Trypanosoma cruzi infection, which is the pathogen responsible for Chagas disease, a neglected tropical parasitic disease native to the Americas that is currently spreading worldwide.

Chronic Kidney Disease (CKD) is a public health problem that presents genetic and environmental risk factors. Two alleles in the Apolipoprotein L1 ( APOL1 ) gene were associated with chronic kidney disease; these alleles are common in individuals of African ancestry but rare in European descendants. Genomic studies on Afro-Americans have indicated a higher prevalence and severity of chronic kidney disease in people of African ancestry when compared to other ethnic groups. However, estimates in low- and middle-income countries are still limited. Precision medicine approaches could improve clinical outcomes in carriers of risk alleles in the Apolipoprotein L1 gene through early diagnosis and specific therapies. Nevertheless, to enhance the definition of studies on these variants, it would be necessary to include individuals with different ancestry profiles in the sample, such as Latinos, African Americans, and Indigenous peoples. There is evidence that measuring genetic ancestry improves clinical care for admixed people. For chronic kidney disease, this knowledge could help establish public health strategies for monitoring patients and understanding the impact of the Apolipoprotein L1 genetic variants in admixed populations. Therefore, researchers need to develop resources, methodologies, and incentives for vulnerable and disadvantaged communities, to develop and implement precision medicine strategies and contribute to consolidating diversity in science and precision medicine in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Giudicelli, De Souza, Veronese, Pereira, Hünemeier and Vianna.)

It has generally been accepted that the current indigenous peoples of the Americas are derived from ancestors from northeastern Asia. The latter were believed to have spread into the American continent by the end of the Last Glacial Maximum. In this sense, a joint and in-depth study of the earliest settlement of East Asia and the Americas is required to elucidate these events accurately. The first Americans underwent an adaptation process to the Americas' vast environmental diversity, mediated by biological and cultural evolution and niche construction, resulting in enormous cultural diversity, a wealth of domesticated species, and extensive landscape modifications. Afterward, in the Late Holocene, the advent of intensive agricultural food production systems, sedentism, and climate change significantly reshaped genetic and cultural diversity across the continent, particularly in the Andes and Amazonia. Furthermore, starting around the end of the 15th century, European colonization resulted in massive extermination of indigenous peoples and extensive admixture. Thus, the present review aims to create a comprehensive picture of the main events involved in the formation of contemporary South American indigenous populations and the dynamics responsible for shaping their genetic diversity by integrating current genetic data with evidence from archeology, linguistics and other disciplines.

Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Here we evaluate the accuracy of prediction for eye, hair and skin pigmentation in a dataset of > 6500 individuals from Mexico, Colombia, Peru, Chile and Brazil (including genome-wide SNP data and quantitative/categorical pigmentation phenotypes - the CANDELA dataset CAN). We evaluated accuracy in relation to different analytical methods and various phenotypic predictors. As expected from statistical principles, we observe that quantitative traits are more sensitive to changes in the prediction models than categorical traits. We find that Random Forest or Linear Regression are generally the best performing methods. We also compare the prediction accuracy of SNP sets defined in the CAN dataset (including 56, 101 and 120 SNPs for eye, hair and skin colour prediction, respectively) to the well-established HIrisPlex-S SNP set (including 6, 22 and 36 SNPs for eye, hair and skin colour prediction respectively). When training prediction models on the CAN data, we observe remarkably similar performances for HIrisPlex-S and the larger CAN SNP sets for the prediction of hair (categorical) and eye (both categorical and quantitative), while the CAN sets outperform HIrisPlex-S for quantitative, but not for categorical skin pigmentation prediction. The performance of HIrisPlex-S, when models are trained in a world-wide sample (although consisting of 80% Europeans, https://hirisplex.erasmusmc.nl), is lower relative to training in the CAN data (particularly for hair and skin colour). Altogether, our observations are consistent with common variation of eye and hair colour having a relatively simple genetic architecture, which is well captured by HIrisPlex-S, even in admixed Latin Americans (with partial European ancestry). By contrast, since skin pigmentation is a more polygenic trait, accuracy is more sensitive to prediction SNP set size, although here this effect was only apparent for a quantitative measure of skin pigmentation. Our results support the use of HIrisPlex-S in the prediction of categorical pigmentation traits for forensic purposes in Latin America, while illustrating the impact of training datasets on its accuracy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Different models have been proposed to elucidate the origins of the founding populations of America, along with the number of migratory waves and routes used by these first explorers. Settlements, both along the Pacific coast and on land, have been evidenced in genetic and archeological studies. However, the number of migratory waves and the origin of immigrants are still controversial topics. Here, we show the Australasian genetic signal is present in the Pacific coast region, indicating a more widespread signal distribution within South America and implicating an ancient contact between Pacific and Amazonian dwellers. We demonstrate that the Australasian population contribution was introduced in South America through the Pacific coastal route before the formation of the Amazonian branch, likely in the ancient coastal Pacific/Amazonian population. In addition, we detected a significant amount of interpopulation and intrapopulation variation in this genetic signal in South America. This study elucidates the genetic relationships of different ancestral components in the initial settlement of South America and proposes that the migratory route used by migrants who carried the Australasian ancestry led to the absence of this signal in the populations of Central and North America., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

We carried out an exhaustive review regarding human skin color variation and how much it may be related to vitamin D metabolism and other photosensitive molecules. We discuss evolutionary contexts that modulate this variability and hypotheses postulated to explain them; for example, a small amount of melanin in the skin facilitates vitamin D production, making it advantageous to have fair skin in an environment with little radiation incidence. In contrast, more melanin protects folate from degradation in an environment with a high incidence of radiation. Some Native American populations have a skin color at odds with what would be expected for the amount of radiation in the environment in which they live, a finding challenging the so-called "vitamin D-folate hypothesis." Since food is also a source of vitamin D, dietary habits should also be considered. Here we argue that a gene network approach provides tools to explain this phenomenon since it indicates potential alleles co-evolving in a compensatory way. We identified alleles of the vitamin D metabolism and pigmentation pathways segregated together, but in different proportions, in agriculturalists and hunter-gatherers. Finally, we highlight how an evolutionary approach can be useful to understand current topics of medical interest., (© 2020 Wiley Periodicals LLC.)

The American continent was the last to be occupied by modern humans, and native populations bear the marks of recent expansions, bottlenecks, natural selection, and population substructure. Here we investigate how this demographic history has shaped genetic variation at the strongly selected HLA loci. In order to disentangle the relative contributions of selection and demography process, we assembled a dataset with genome-wide microsatellites and HLA-A, -B, -C, and -DRB1 typing data for a set of 424 Native American individuals. We find that demographic history explains a sizeable fraction of HLA variation, both within and among populations. A striking feature of HLA variation in the Americas is the existence of alleles which are present in the continent but either absent or very rare elsewhere in the world. We show that this feature is consistent with demographic history (i.e., the combination of changes in population size associated with bottlenecks and subsequent population expansions). However, signatures of selection at HLA loci are still visible, with significant evidence selection at deeper timescales for most loci and populations, as well as population differentiation at HLA loci exceeding that seen at neutral markers., Competing Interests: The authors have declared that no competing interests exist.

In the post-genomic era, genomic medicine interventions as a key component of personalized medicine and tailored-made health care are greatly anticipated following recent scientific and technological advances. Indeed, large-scale sequencing efforts that explore human genomic variation have been initiated in several, mostly developed, countries across the globe, such as the United States, the United Kingdom, and a few others. Here, we highlight the successful implementation of large-scale national genomic initiatives, namely the Genome of Greece (GoGreece) and the DNA do Brasil (DNABr), aiming to emphasize the importance of implementing such initiatives in developing countries. Based on this experience, we also provide a roadmap for replicating these projects in other low-resource settings, thereby bringing genomic medicine in these countries closer to clinical fruition., (Copyright © 2020 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Over the past few years, tools capable of predicting pigmentation phenotypes have been developed aiming to contribute for criminal and anthropological investigations. In this study, we used eight genetic systems to infer eye, hair, and skin color of ancient and contemporary Native Americans. To achieve this goal, we retrieved 61 SNPs from 42 samples available in free online repositories of DNA sequences. We performed pigmentation predictions using two freely available tools, HIrisPlex-S and Snipper, in addition to two other published models. This workflow made possible to predict all three phenotypes with at least one tool for 29 out of the 42 samples. Considering these 29 individuals, predictions for eye, hair, and skin color were obtained with HIrisPlex-S for 27, 28 and 27 individuals, respectively, while 24, 25 and 25 individuals had such predictions with Snipper. In general, ancient and contemporary Native Americans were predicted to have intermediate/brown eyes, black hair, and intermediate/darker skin pigmentation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare no competing interest.

After the colonization of the Americas by Europeans and the consequent Trans-Atlantic Slave Trade, most Native American populations in eastern Brazil disappeared or went through an admixture process that configured a population composed of three main genetic components: the European, the sub-Saharan African, and the Native American. The study of the Native American genetic history is challenged by the lack of availability of genome-wide samples from Native American populations, the technical difficulties to develop ancient DNA studies, and the low proportions of the Native American component in the admixed Brazilian populations (on average 7%). We analyzed genome-wide data of 5,825 individuals from three locations of eastern Brazil: Salvador (North-East), Bambui (South-East), and Pelotas (South) and we reconstructed populations that emulate the Native American groups that were living in the 16th century around the sampling locations. This genetic reconstruction was performed after local ancestry analysis of the admixed Brazilian populations, through the rearrangement of the Native American haplotypes into reconstructed individuals with full Native American ancestry (51 reconstructed individuals in Salvador, 45 in Bambui, and 197 in Pelotas). We compared the reconstructed populations with nonadmixed Native American populations from other regions of Brazil through haplotype-based methods. Our results reveal a population structure shaped by the dichotomy of Tupi-/Jê-speaking ancestry related groups. We also show evidence of a decrease of the diversity of nonadmixed Native American groups after the European contact, in contrast with the reconstructed populations, suggesting a reservoir of the Native American genetic diversity within the admixed Brazilian population., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample.

We report genome-wide ancient DNA from 49 individuals forming four parallel time transects in Belize, Brazil, the Central Andes, and the Southern Cone, each dating to at least ∼9,000 years ago. The common ancestral population radiated rapidly from just one of the two early branches that contributed to Native Americans today. We document two previously unappreciated streams of gene flow between North and South America. One affected the Central Andes by ∼4,200 years ago, while the other explains an affinity between the oldest North American genome associated with the Clovis culture and the oldest Central and South Americans from Chile, Brazil, and Belize. However, this was not the primary source for later South Americans, as the other ancient individuals derive from lineages without specific affinity to the Clovis-associated genome, suggesting a population replacement that began at least 9,000 years ago and was followed by substantial population continuity in multiple regions., (Published by Elsevier Inc.)

The Andean Altiplano has been occupied continuously since the late Pleistocene, ~12,000 years ago, which places the Andean natives as one of the most ancient populations living at high altitudes. In the present study, we analyzed genomic data from Native Americans living a long-time at Andean high altitude and at Amazonia and Mesoamerica lowland areas. We have identified three new candidate genes - SP100, DUOX2 and CLC - with evidence of positive selection for altitude adaptation in Andeans. These genes are involved in the TP53 pathway and are related to physiological routes important for high-altitude hypoxia response, such as those linked to increased angiogenesis, skeletal muscle adaptations, and immune functions at the fetus-maternal interface. Our results, combined with other studies, showed that Andeans have adapted to the Altiplano in different ways and using distinct molecular strategies as compared to those of other natives living at high altitudes.

Establishing the genetic basis that underlies craniofacial variability in natural populations is one of the main topics of evolutionary and developmental studies. One of the genes associated with mammal craniofacial variability is RUNX2, and in the present study we investigated the association between craniofacial length and width and RUNX2 across New World bats (Phyllostomidae) and primates (Catarrhini and Platyrrhini). Our results showed contrasting patterns of association between the glutamate/alanine ratios (Q/A ratio) and palate shape in these highly diverse groups. In phyllostomid bats, we found an association between shorter/broader faces and increase of the Q/A ratio. In New World monkeys (NWM) there was a positive correlation of increasing Q/A ratios to more elongated faces. Our findings reinforced the role of the Q/A ratio as a flexible genetic mechanism that would rapidly change the time of skull ossification throughout development. However, we propose a scenario in which the influence of this genetic adjustment system is indirect. The Q/A ratio would not lead to a specific phenotype, but throughout the history of a lineage, would act along with evolutionary constraints, as well as other genes, as a facilitator for adaptive morphological changes.

Facial asymmetries are usually measured and interpreted as proxies to developmental noise. However, analyses focused on its developmental and genetic architecture are scarce. To advance on this topic, studies based on a comprehensive and simultaneous analysis of modularity, morphological integration and facial asymmetries including both phenotypic and genomic information are needed. Here we explore several modularity hypotheses on a sample of Latin American mestizos, in order to test if modularity and integration patterns differ across several genomic ancestry backgrounds. To do so, 4104 individuals were analyzed using 3D photogrammetry reconstructions and a set of 34 facial landmarks placed on each individual. We found a pattern of modularity and integration that is conserved across sub-samples differing in their genomic ancestry background. Specifically, a signal of modularity based on functional demands and organization of the face is regularly observed across the whole sample. Our results shed more light on previous evidence obtained from Genome Wide Association Studies performed on the same samples, indicating the action of different genomic regions contributing to the expression of the nose and mouth facial phenotypes. Our results also indicate that large samples including phenotypic and genomic metadata enable a better understanding of the developmental and genetic architecture of craniofacial phenotypes.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia and epilepsy. The disease is caused by a pentanucleotide ATTCT expansion in intron 9 of the ATXN10 gene on chromosome 22q13.3. SCA10 has shown a geographical distribution throughout America with a likely degree of Amerindian ancestry from different countries so far. Currently available data suggest that SCA10 mutation might have spread out early during the peopling of the Americas. However, the ancestral origin of SCA10 mutation remains under speculation. Samples of SCA10 patients from two Latin American countries were analysed, being 16 families from Brazil (29 patients) and 21 families from Peru (27 patients) as well as 49 healthy individuals from Indigenous Quechua population and 51 healthy Brazilian individuals. Four polymorphic markers spanning a region of 5.2 cM harbouring the ATTCT expansion were used to define the haplotypes, which were genotyped by different approaches. Our data have shown that 19-CGGC-14 shared haplotype was found in 47% of Brazilian and in 63% of Peruvian families. Frequencies from both groups are not statistically different from Quechua controls (57%), but they are statistically different from Brazilian controls (12%) (p < 0.001). The most frequent expanded haplotype in Quechuas, 19-15-CGGC-14-10, is found in 50% of Brazilian and in 65% of Peruvian patients with SCA10. These findings bring valuable evidence that ATTCT expansion may have arisen in a Native American chromosome.

Objectives: To determine genetic differences between agriculturalist and hunter-gatherer southern Native American populations for selected metabolism-related markers and to test whether Neel's thrifty genotype hypothesis (TGH) could explain the genetic patterns observed in these populations., Materials and Methods: 375 Native South American individuals from 17 populations were genotyped using six markers (APOE rs429358 and rs7412; APOA2 rs5082; CD36 rs3211883; TCF7L2 rs11196205; and IGF2BP2 rs11705701). Additionally, APOE genotypes from 39 individuals were obtained from the literature. AMOVA, main effects, and gene-gene interaction tests were performed., Results: We observed differences in allele distribution patterns between agriculturalists and hunter-gatherers for some markers. For instance, between-groups component of genetic variance (F CT ) for APOE rs429358 showed strong differences in allelic distributions between hunter-gatherers and agriculturalists (p = 0.00196). Gene-gene interaction analysis indicated that the APOE E4/CD36 TT and APOE E4/IGF2BP2 A carrier combinations occur at a higher frequency in hunter-gatherers, but this combination is not replicated in archaic (Neanderthal and Denisovan) and ancient (Anzick, Saqqaq, Ust-Ishim, Mal'ta) hunter-gatherer individuals., Discussion: A complex scenario explains the observed frequencies of the tested markers in hunter-gatherers. Different factors, such as pleotropic alleles, rainforest selective pressures, and population dynamics, may be collectively shaping the observed genetic patterns. We conclude that although TGH seems a plausible hypothesis to explain part of the data, other factors may be important in our tested populations., (© 2017 Wiley Periodicals, Inc.)

When humans moved from Asia toward the Americas over 18,000 y ago and eventually peopled the New World they encountered a new environment with extreme climate conditions and distinct dietary resources. These environmental and dietary pressures may have led to instances of genetic adaptation with the potential to influence the phenotypic variation in extant Native American populations. An example of such an event is the evolution of the fatty acid desaturases ( FADS ) genes, which have been claimed to harbor signals of positive selection in Inuit populations due to adaptation to the cold Greenland Arctic climate and to a protein-rich diet. Because there was evidence of intercontinental variation in this genetic region, with indications of positive selection for its variants, we decided to compare the Inuit findings with other Native American data. Here, we use several lines of evidence to show that the signal of FADS-positive selection is not restricted to the Arctic but instead is broadly observed throughout the Americas. The shared signature of selection among populations living in such a diverse range of environments is likely due to a single and strong instance of local adaptation that took place in the common ancestral population before their entrance into the New World. These first Americans peopled the whole continent and spread this adaptive variant across a diverse set of environments.