Strong Effect of Demographic Changes on Tuberculosis Susceptibility in South Africa.

South Africa is among the world's top eight TB burden countries, and despite a focus on HIV-TB co-infection, most of the population living with TB are not HIV co-infected. The disease is endemic across the country with 80-90% exposure by adulthood. We investigated epidemiological risk factors for tuberculosis (TB) in the Northern Cape Province, South Africa: an understudied TB endemic region with extreme TB incidence (645/100,000) and the lowest provincial population density. We leveraged the population's high TB incidence and community transmission to design a case-control study with population-based controls, reflecting similar mechanisms of exposure between the groups. We recruited 1,126 participants with suspected TB from 12 community health clinics, and generated a cohort of 878 individuals (cases =374, controls =504) after implementing our enrollment criteria. All participants were GeneXpert Ultra tested for active TB by a local clinic. We assessed important risk factors for active TB using logistic regression and random forest modeling. Additionally, a subset of individuals were genotyped to determine genome-wide ancestry components. Male gender had the strongest effect on TB risk (OR: 2.87 [95% CI: 2.1-3.8]); smoking and alcohol consumption did not significantly increase TB risk. We identified two interactions: age by socioeconomic status (SES) and birthplace by residence locality on TB risk (OR = 3.05, p = 0.016) - where rural birthplace but town residence was the highest risk category. Finally, participants had a majority Khoe-San ancestry, typically greater than 50%. Epidemiological risk factors for this cohort differ from other global populations. The significant interaction effects reflect rapid changes in SES and mobility over recent generations and strongly impact TB risk in the Northern Cape of South Africa. Our models show that such risk factors combined explain 16% of the variance (r2) in case/control status.

Persistence of Matrilocal Postmarital Residence Across Multiple Generations in Southern Africa.

Factors such as subsistence turnover, warfare, or interaction between different groups can be major sources of cultural change in human populations. Global demographic shifts such as the transition to agriculture during the Neolithic and more recently the urbanization and globalization of the twentieth century have been major catalysts for cultural change. Here, we test whether cultural traits such as patri/matrilocality and postmarital migration persist in the face of social upheaval and gene flow during the past 150 years in postcolonial South Africa. The recent history of South Africa has seen major demographic shifts that resulted in the displacement and forced sedentism of indigenous Khoekhoe and San populations. During the expansion of the colonial frontier, the Khoe-San admixed with European colonists and enslaved individuals from West/Central Africa, Indonesia, and South Asia, introducing novel cultural norms. We conducted demographic interviews among Nama and Cederberg communities representing nearly 3,000 individuals across three generations. Despite the history of colonial expansion, and the subsequent incorporation of Khoe-San and Khoe-San-descendant communities into a colonial society with strong patrilocal norms, patrilocality is the least common postmarital residence pattern in our study populations today. Our results suggest that more recent forces of integration into the market economy are likely the primary drivers of change in the cultural traits examined in our study. Birthplace had a strong effect on an individual's odds of migration, distance moved, and postmarital residence form. These effects are at least partially explained by the population size of the birthplace. Our results suggest that market factors local to birthplaces are important drivers of residence decisions, although the frequency of matrilocal residence and a geographic and temporal cline in migration and residence patterns also indicate the persistence of some historic Khoe-San cultural traits in contemporary groups.

Epidemiological correlates of overweight and obesity in the Northern Cape Province, South Africa.

Background: In the past several decades, obesity has become a major public health issue worldwide, associated with increased rates of chronic disease and death. Like many developing nations, South Africa is experiencing rapid increases in BMI, and as a result, evidence-based preventive strategies are needed to reduce the increasing burden of overweight and obesity. This study aimed to determine the prevalence and predictors of overweight and obesity among a multi-ethnic cohort from the rural Northern Cape of South Africa. Methods: These data were collected as part of a tuberculosis (TB) case-control study, with 395 healthy control participants included in the final analysis. Overweight and obesity were defined according to WHO classification. Multivariate linear models of BMI were generated using sex, age, education level, smoking, alcohol consumption, and diabetes as predictor variables. We also used multivariable logistic regression analysis to assess the relationship of these factors with overweight and obesity. Results: The average BMI in our study cohort was 25.2. The prevalence of overweight was 18.0% and the prevalence of obesity was 25.0%. We find that female sex, being older, having more years of formal education, having diabetes, and being in a rural area are all positively associated with BMI in our dataset. Women (OR = 5.6, 95% CI [3.3-9.8]), rural individuals (OR = 3.3, 95% CI [1.9-6.0]), older individuals (OR = 1.02, 95% CI [1-1.04]), and those with more years of education (OR = 1.2, 95% CI [1.09-1.32]) were all more likely to be overweight or obese. Alternatively, being a smoker is negatively associated with BMI and decreases one's odds of being overweight or obese (OR = 0.28, 95% CI [0.16-0.46]). Conclusions: We observed a high prevalence of overweight and obesity in this study. The odds of being overweight and obese were higher in women, those living in rural areas, and those with more education, and increases with age. Community-based interventions to control obesity in this region should pay special attention to these groups.

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.

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.

Hunter-gatherer genomes reveal diverse demographic trajectories during the rise of farming in Eastern Africa.

The fate of hunting and gathering populations following the rise of agriculture and pastoralism remains a topic of debate in the study of human prehistory. Studies of ancient and modern genomes have found that autochthonous groups were largely replaced by expanding farmer populations with varying levels of gene flow, a characterization that is influenced by the almost universal focus on the European Neolithic.1-5 We sought to understand the demographic impact of an ongoing cultural transition to farming in Southwest Ethiopia, one of the last regions in Africa to experience such shifts.6 Importantly, Southwest Ethiopia is home to several of the world's remaining hunter-gatherer groups, including the Chabu people, who are currently transitioning away from their traditional mode of subsistence.7 We generated genome-wide data from the Chabu and four neighboring populations, the Majang, Shekkacho, Bench, and Sheko, to characterize their genetic ancestry and estimate their effective population sizes over the last 60 generations. We show that the Chabu are a distinct population closely related to ancient people who occupied Southwest Ethiopia >4,500 years ago. Furthermore, the Chabu are undergoing a severe population bottleneck, which began approximately 1,400 years ago. By analyzing eleven Eastern African populations, we find evidence for divergent demographic trajectories among hunter-gatherer-descendant groups. Our results illustrate that although foragers respond to encroaching agriculture and pastoralism with multiple strategies, including cultural adoption of agropastoralism, gene flow, and economic specialization, they often face population decline.

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.

Ancient DNA Reconstructs the Genetic Legacies of Precontact Puerto Rico Communities.

Indigenous peoples have occupied the island of Puerto Rico since at least 3000 BC. Due to the demographic shifts that occurred after European contact, the origin(s) of these ancient populations, and their genetic relationship to present-day islanders, are unclear. We use ancient DNA to characterize the population history and genetic legacies of precontact Indigenous communities from Puerto Rico. Bone, tooth, and dental calculus samples were collected from 124 individuals from three precontact archaeological sites: Tibes, Punta Candelero, and Paso del Indio. Despite poor DNA preservation, we used target enrichment and high-throughput sequencing to obtain complete mitochondrial genomes (mtDNA) from 45 individuals and autosomal genotypes from two individuals. We found a high proportion of Native American mtDNA haplogroups A2 and C1 in the precontact Puerto Rico sample (40% and 44%, respectively). This distribution, as well as the haplotypes represented, supports a primarily Amazonian South American origin for these populations and mirrors the Native American mtDNA diversity patterns found in present-day islanders. Three mtDNA haplotypes from precontact Puerto Rico persist among Puerto Ricans and other Caribbean islanders, indicating that present-day populations are reservoirs of precontact mtDNA diversity. Lastly, we find similarity in autosomal ancestry patterns between precontact individuals from Puerto Rico and the Bahamas, suggesting a shared component of Indigenous Caribbean ancestry with close affinity to South American populations. Our findings contribute to a more complete reconstruction of precontact Caribbean population history and explore the role of Indigenous peoples in shaping the biocultural diversity of present-day Puerto Ricans and other Caribbean islanders.

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.

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.