Rights, interests and expectations: Indigenous perspectives on unrestricted access to genomic data.

Addressing Indigenous rights and interests in genetic resources has become increasingly challenging in an open science environment that promotes unrestricted access to genomic data. Although Indigenous experiences with genetic research have been shaped by a series of negative interactions, there is increasing recognition that equitable benefits can only be realized through greater participation of Indigenous communities. Issues of trust, accountability and equity underpin Indigenous critiques of genetic research and the sharing of genomic data. This Perspectives article highlights identified issues for Indigenous communities around the sharing of genomic data and suggests principles and actions that genomic researchers can adopt to recognize community rights and interests in data.

Palaeo-Eskimo genetic ancestry and the peopling of Chukotka and North America.

Much of the American Arctic was first settled 5,000 years ago, by groups of people known as Palaeo-Eskimos. They were subsequently joined and largely displaced around 1,000 years ago by ancestors of the present-day Inuit and Yup'ik1-3. The genetic relationship between Palaeo-Eskimos and Native American, Inuit, Yup'ik and Aleut populations remains uncertain4-6. Here we present genomic data for 48 ancient individuals from Chukotka, East Siberia, the Aleutian Islands, Alaska, and the Canadian Arctic. We co-analyse these data with data from present-day Alaskan Iñupiat and West Siberian populations and published genomes. Using methods based on rare-allele and haplotype sharing, as well as established techniques4,7-9, we show that Palaeo-Eskimo-related ancestry is ubiquitous among people who speak Na-Dene and Eskimo-Aleut languages. We develop a comprehensive model for the Holocene peopling events of Chukotka and North America, and show that Na-Dene-speaking peoples, people of the Aleutian Islands, and Yup'ik and Inuit across the Arctic region all share ancestry from a single Palaeo-Eskimo-related Siberian source.

Fostering Responsible Research on Ancient DNA.

Anticipating and addressing the social implications of scientific work is a fundamental responsibility of all scientists. However, expectations for ethically sound practices can evolve over time as the implications of science come to be better understood. Contemporary researchers who work with ancient human remains, including those who conduct ancient DNA research, face precisely this challenge as it becomes clear that practices such as community engagement are needed to address the important social implications of this work. To foster and promote ethical engagement between researchers and communities, we offer five practical recommendations for ancient DNA researchers: (1) formally consult with communities; (2) address cultural and ethical considerations; (3) engage communities and support capacity building; (4) develop plans to report results and manage data; and (5) develop plans for long-term responsibility and stewardship. Ultimately, every member of a research team has an important role in fostering ethical research on ancient DNA.

Parallel evolution in human populations: A biocultural perspective.

Parallel evolution-where different populations evolve similar traits in response to similar environments-has been a topic of growing interest to biologists and biological anthropologists for decades. Parallel evolution occurs in human populations thanks to myriad biological and cultural mechanisms that permit humans to survive and thrive in diverse environments worldwide. Because humans shape and are shaped by their environments, biocultural approaches that emphasize the interconnections between biology and culture are key to understanding parallel evolution in human populations as well as the nuances of human biological variation and adaptation. In this review, we discuss how biocultural theory has been and can be applied to studies of parallel evolution and adaptation more broadly. We illustrate this through four examples of parallel evolution in humans: malaria resistance, lactase persistence, cold tolerance, and high-altitude adaptation.

Comparing signals of natural selection between three Indigenous North American populations.

While many studies have highlighted human adaptations to diverse environments worldwide, genomic studies of natural selection in Indigenous populations in the Americas have been absent from this literature until very recently. Since humans first entered the Americas some 20,000 years ago, they have settled in many new environments across the continent. This diversity of environments has placed variable selective pressures on the populations living in each region, but the effects of these pressures have not been extensively studied to date. To help fill this gap, we collected genome-wide data from three Indigenous North American populations from different geographic regions of the continent (Alaska, southeastern United States, and central Mexico). We identified signals of natural selection in each population and compared signals across populations to explore the differences in selective pressures among the three regions sampled. We find evidence of adaptation to cold and high-latitude environments in Alaska, while in the southeastern United States and central Mexico, pathogenic environments seem to have created important selective pressures. This study lays the foundation for additional functional and phenotypic work on possible adaptations to varied environments during the history of population diversification in the Americas.

Chaco Canyon Dig Unearths Ethical Concerns.

The field of paleogenomics (the study of ancient genomes) is rapidly advancing, with more robust methods of isolating ancient DNA and increasing access to next-generation DNA sequencing technology. As these studies progress, many important ethical issues have emerged that should be considered when ancient Native American remains, whom we refer to as ancestors, are used in research. We highlight a 2017 article by Kennett et al., "Archaeogenomic evidence reveals prehistoric matrilineal dynasty," that brings to light several ethical issues that should be addressed in paleogenomics research. The study helps elucidate the matrilineal relationships in ancient Chacoan society through ancient DNA analysis. However, we, as Indigenous researchers and allies, raise ethical concerns with the study's scientific conclusions that can be problematic for Native American communities: (1) the lack of tribal consultation, (2) the use of culturally insensitive descriptions, and (3) the potential impact on marginalized groups. Further, we explore the limitations of the Native American Graves Protection and Repatriation Act, which addresses repatriation but not research, because clear ethical guidelines have not been established for research involving Native American ancestors, especially those deemed "culturally unaffiliated." Multiple studies of "culturally unaffiliated" remains have been initiated recently, so it is imperative that researchers consider the ethical ramifications of paleogenomics research. Past research indiscretions have created a history of mistrust and exploitation in many Native American communities. To promote ethical engagement of Native American communities in research, we therefore suggest careful attention to ethical considerations, strong tribal consultation requirements, and greater collaborations among museums, federal agencies, researchers, scientific journals, and granting agencies.

Combating Racial Health Disparities Through Medical Education: The Need for Anthropological and Genetic Perspectives in Medical Training.

Despite major public health initiatives, significant disparities persist among racially and ethnically defined groups in the prevalence of disease, access to medical care, quality of medical care, and health outcomes for common causes of morbidity and mortality in the United States. It is critical that we develop new and creative strategies to address such inequities; mitigate the social, environmental, institutional, and genetic determinants of poor health; and combat the persistence of racial profiling in clinical contexts that further exacerbates racial/ethnic health disparities. This article argues that medical education is a prime target for intervention and that anthropologists and human population geneticists should play a role in efforts to reform US medical curricula. Medical education would benefit greatly by incorporating anthropological and genetic perspectives on the complexities of race, human genetic variation, epigenetics, and the causes of racial/ethnic disparities. Medical students and practicing physicians should also receive training on how to use this knowledge to improve clinical practice, diagnosis, and treatment for racially diverse populations.

Ancient DNA from the Schild site in Illinois: Implications for the Mississippian transition in the Lower Illinois River Valley.

Archaeologists have long debated whether rapid cultural change in the archaeological record is due to in situ developments, migration of a new group into the region, or the spread of new cultural practices into an area through existing social networks, with the local peoples adopting and adapting practices from elsewhere as they see fit (acculturation). Researchers have suggested each of these explanations for the major cultural transition that occurred at the beginning of the Mississippian period (AD 1050) across eastern North America. In this study, we used ancient DNA to test competing hypotheses of migration and acculturation for the culture change that occurred between the Late Woodland (AD 400-1050) and Mississippian (AD 1050-1500) periods in the Lower Illinois River Valley. We obtained sequences of the first hypervariable segment of the mitochondrial genome (mtDNA) from 39 individuals (17 Late Woodland, 22 Mississippian) interred in the Schild cemetery in western Illinois, and compared these lineages to ancient mtDNA lineages present at other sites in the region. Computer simulations were used to test a null hypothesis of population continuity from Late Woodland to Mississippian times at the Schild site and to investigate the possibility of gene flow from elsewhere in the region. Our results suggest that the Late Woodland to Mississippian cultural transition at Schild was not due to an influx of people from elsewhere. Instead, it is more likely that the transition to Mississippian cultural practices at this site was due to a process of acculturation.

Nocturnal light environments influence color vision and signatures of selection on the OPN1SW opsin gene in nocturnal lemurs.

Although loss of short-wavelength-sensitive (SWS) cones and dichromatic color vision in mammals has traditionally been linked to a nocturnal lifestyle, recent studies have identified variation in selective pressure for the maintenance of the OPN1SW opsin gene (and thus, potentially dichromacy) among nocturnal mammalian lineages. These studies hypothesize that purifying selection to retain SWS cones may be associated with a selective advantage for nocturnal color vision under certain ecological conditions. In this study, we explore the effect of nocturnal light environment on OPN1SW opsin gene evolution in a diverse sample of nocturnal lemurs (106 individuals, 19 species, and 5 genera). Using both phylogenetic and population genetic approaches, we test whether species from closed canopy rainforests, which are impoverished in short-wavelength light, have experienced relaxed selection compared with species from open canopy forests. We identify clear signatures of differential selection on OPN1SW by habitat type. Our results suggest that open canopy species generally experience strong purifying selection to maintain SWS cones. In contrast, closed canopy species experience weaker purifying selection or a relaxation of selection on OPN1SW. We also found evidence of nonfunctional OPN1SW genes in all Phaner species and in Cheirogaleus medius, implying at least three independent losses of SWS cones in cheirogaleids. Our results suggest that the evolution of color vision in nocturnal lemurs has been influenced by nocturnal light environment.

Brief communication: Evolution of a specific O allele (O1vG542A) supports unique ancestry of Native Americans.

In this study, we explore the geographic and temporal distribution of a unique variant of the O blood group allele called O1v(G542A) , which has been shown to be shared among Native Americans but is rare in other populations. O1v(G542A) was previously reported in Native American populations in Mesoamerica and South America, and has been proposed as an ancestry informative marker. We investigated whether this allele is also found in the Tlingit and Haida, two contemporary indigenous populations from Alaska, and a pre-Columbian population from California. If O1v(G542A) is present in Na-Dene speakers (i.e., Tlingits), it would indicate that Na-Dene speaking groups share close ancestry with other Native American groups and support a Beringian origin of the allele, consistent with the Beringian Incubation Model. If O1v(G542A) is found in pre-Columbian populations, it would further support a Beringian origin of the allele, rather than a more recent introduction of the allele into the Americas via gene flow from one or more populations which have admixed with Native Americans over the past five centuries. We identified this allele in one Na-Dene population at a frequency of 0.11, and one ancient California population at a frequency of 0.20. Our results support a Beringian origin of O1v(G542A) , which is distributed today among all Native American groups that have been genotyped in appreciable numbers at this locus. This result is consistent with the hypothesis that Na-Dene and other Native American populations primarily derive their ancestry from a single source population.

Evaluating population histories in Patagonia and Tierra del Fuego, Chile, using ancient mitochondrial and Y-chromosomal DNA.

OBJECTIVES: This study aims to characterize the genetic histories of ancient hunter-gatherer groups in Fuego-Patagonia (Chile) with distinct Marine, Terrestrial, and Mixed Economy subsistence strategies. Mitochondrial (mtDNA) and Y-chromosome data were generated to test three hypotheses. H0: All individuals were drawn from the same panmictic population; H1: Terrestrial groups first populated the region and gave rise to highly specialized Marine groups by ~7,500 cal BP; or H2: Marine and Terrestrial groups represent distinct ancestral lineages who migrated independently into the region. METHODS: Ancient DNA was extracted from the teeth of 50 Fuegian-Patagonian individuals dating from 6,895 cal BP to after European arrival, and analyzed alongside other individuals from previous studies. Individuals were assigned to Marine, Terrestrial, and Mixed Economy groups based on archeological context and stable isotope diet inferences, and mtDNA (HVR1/2) and Y-chromosome variation was analyzed. RESULTS: Endogenous aDNA was obtained from 49/50 (98%) individuals. Haplotype diversities, FST comparisons, and exact tests of population differentiation showed that Marine groups were significantly different from Terrestrial groups based on mtDNA (p < 0.05). No statistically significant differences were found between Terrestrial and Mixed Economy groups. Demographic simulations support models in which Marine groups diverged from the others by ~14,000 cal BP. Y-chromosome results showed similar patterns but were not statistically significant due to small sample sizes and allelic dropout. DISCUSSION: These results support the hypothesis that Marine and Terrestrial economic groups represent distinct ancestral lineages who diverged during the time populations were expanding in the Americas, and may represent independent migrations into Fuego-Patagonia.

The genetic impact of Aztec imperialism: ancient mitochondrial DNA evidence from Xaltocan, Mexico.

In AD 1428, the city-states of Tenochtitlan, Texcoco, and Tlacopan formed the Triple Alliance, laying the foundations of the Aztec empire. Although it is well documented that the Aztecs annexed numerous polities in the Basin of Mexico over the following years, the demographic consequences of this expansion remain unclear. At the city-state capital of Xaltocan, 16th century documents suggest that the site's conquest and subsequent incorporation into the Aztec empire led to a replacement of the original Otomí population, whereas archaeological evidence suggests that some of the original population may have remained at the town under Aztec rule. To help address questions about Xaltocan's demographic history during this period, we analyzed ancient DNA from 25 individuals recovered from three houses rebuilt over time and occupied between AD 1240 and 1521. These individuals were divided into two temporal groups that predate and postdate the site's conquest. We determined the mitochondrial DNA haplogroup of each individual and identified haplotypes based on 372 base pair sequences of first hypervariable region. Our results indicate that the residents of these houses before and after the Aztec conquest have distinct haplotypes that are not closely related, and the mitochondrial compositions of the temporal groups are statistically different. Altogether, these results suggest that the matrilines present in the households were replaced following the Aztec conquest. This study therefore indicates that the Aztec expansion may have been associated with significant demographic and genetic changes within Xaltocan.

Nondestructive sampling of human skeletal remains yields ancient nuclear and mitochondrial DNA.

Museum curators and living communities are sometimes reluctant to permit ancient DNA (aDNA) studies of human skeletal remains because the extraction of aDNA usually requires the destruction of at least some skeletal material. Whether these views stem from a desire to conserve precious materials or an objection to destroying ancestral remains, they limit the potential of aDNA research. To help address concerns about destructive analysis and to minimize damage to valuable specimens, we describe a nondestructive method for extracting DNA from ancient human remains. This method can be used with both teeth and bone, but it preserves the structural integrity of teeth much more effectively than that of bone. Using this method, we demonstrate that it is possible to extract both mitochondrial and nuclear DNA from human remains dating between 300 BC and 1600 AD. Importantly, the method does not expose the remains to hazardous chemicals, allowing them to be safely returned to curators, custodians, and/or owners of the samples. We successfully amplified mitochondrial DNA from 90% of the individuals tested, and we were able to analyze 1-9 nuclear loci in 70% of individuals. We also show that repeated nondestructive extractions from the same tooth can yield amplifiable mitochondrial and nuclear DNA. The high success rate of this method and its ability to yield DNA from samples spanning a wide geographic and temporal range without destroying the structural integrity of the sampled material may make possible the genetic study of skeletal collections that are not available for destructive analysis.

Unraveling Signatures of Local Adaptation among Indigenous Groups from Mexico.

Few studies have addressed how selective pressures have shaped the genetic structure of the current Native American populations, and they have mostly limited their inferences to admixed Latin American populations. Here, we searched for local adaptation signals, based on integrated haplotype scores and population branch statistics, in 325 Mexican Indigenous individuals with at least 99% Native American ancestry from five previously defined geographical regions. Although each region exhibited its own local adaptation profile, only PPARG and AJAP1, both negative regulators of the Wnt/ß catenin signaling pathway, showed significant adaptation signals in all the tested regions. Several signals were found, mainly in the genes related to the metabolic processes and immune response. A pathway enrichment analysis revealed the overrepresentation of selected genes related to several biological phenotypes/conditions, such as the immune response and metabolic pathways, in agreement with previous studies, suggesting that immunological and metabolic pressures are major drivers of human adaptation. Genes related to the gut microbiome measurements were overrepresented in all the regions, highlighting the importance of studying how humans have coevolved with the microbial communities that colonize them. Our results provide a further explanation of the human evolutionary history in response to environmental pressures in this region.

Ancient DNA perspectives on American colonization and population history.

Ancient DNA (aDNA) analyses have proven to be important tools in understanding human population dispersals, settlement patterns, interactions between prehistoric populations, and the development of regional population histories. Here, we review the published results of sixty-three human populations from throughout the Americas and compare the levels of diversity and geographic patterns of variation in the ancient samples with contemporary genetic variation in the Americas in order to investigate the evolution of the Native American gene pool over time. Our analysis of mitochondrial haplogroup frequencies and prehistoric population genetic diversity presents a complex evolutionary picture. Although the broad genetic structure of American prehistoric populations appears to have been established relatively early, we nevertheless identify examples of genetic discontinuity over time in select regions. We discuss the implications this finding may have for our interpretation of the genetic evidence for the initial colonization of the Americas and its subsequent population history.

The genomic landscape of Mexican Indigenous populations brings insights into the peopling of the Americas.

The genetic makeup of Indigenous populations inhabiting Mexico has been strongly influenced by geography and demographic history. Here, we perform a genome-wide analysis of 716 newly genotyped individuals from 60 of the 68 recognized ethnic groups in Mexico. We show that the genetic structure of these populations is strongly influenced by geography, and our demographic reconstructions suggest a decline in the population size of all tested populations in the last 15-30 generations. We find evidence that Aridoamerican and Mesoamerican populations diverged roughly 4-9.9 ka, around the time when sedentary farming started in Mesoamerica. Comparisons with ancient genomes indicate that the Upward Sun River 1 (USR1) individual is an outgroup to Mexican/South American Indigenous populations, whereas Anzick-1 was more closely related to Mesoamerican/South American populations than to those from Aridoamerica, showing an even more complex history of divergence than recognized so far.