Admixture's impact on Brazilian population evolution and health.

Brazil, the largest Latin American country, is underrepresented in genomic research despite boasting the world's largest recently admixed population. In this study, we generated 2723 high-coverage whole-genome sequences from the Brazilian population, including urban, rural, and riverine communities representing diverse ethnic backgrounds. We reveal the impressive genomic diversity of Brazilians, identifying >8 million previously unknown variants, including 36,637 predicted deleterious and potentially affecting population health. We found a positive correlation between these deleterious variants and ancestry. Brazilian genomes are a global haplotype mosaic shaped by nonrandom mating, with peak admixture in the 18th and 19th centuries. Within this diversity, ancestry-specific haplotypes exhibit an uneven spatiotemporal distribution. We also identified putatively selected genes in this diverse population, primarily linked to fertility, immune response, and metabolic traits. Editor's summary: Many medically relevant traits, such as drug metabolism, are characterized by some genetic variants having relatively large effects. However, it can be difficult to identify such variants when the genetic variation of a population is not well understood. Nunes et al. generated whole-genome sequence data for 2723 healthy individuals across Brazil, a population characterized by recent and unequal admixture among Indigenous Americans, Europeans, and African enslaved people. They identified nearly 9 million previously unreported genetic variants, including some predicted to negatively affect protein function, and used these data to refine admixture timing estimates. These data represent an important step toward ameliorating the disparities in genomic coverage between populations. —Corinne Simonti INTRODUCTION: Brazil is a vast continental country home to the largest population in Latin America and boasts the world's largest recently admixed population. The colonization process brought ∼5 million Europeans to Brazil, alongside the forced migration of at least 5 million Africans and the decimation of Indigenous populations, which once included >10 million people speaking more than 1000 languages. This distinctive historical interplay shaped a complex mosaic of genetic diversity, underscoring the importance of detailed genomic studies. However, similar to other populations in the Global South, the Brazilian population remains notably underrepresented in genomic research, where there is a lack of studies investigating the effects of this population's admixture on its evolution, diversity, and health status. RATIONALE: To address these gaps, we generated 2723 high-coverage whole-genome sequences of the Brazilian population, encompassing urban, rural, and riverine communities from all five geographical regions of Brazil. This dataset reflects a diverse group of ethnic backgrounds, including Afro-Brazilians and descendants of Indigenous people, and provides a comprehensive representation of Brazilian genomic diversity. Advanced methods, such as local ancestry inference and haplotype-based analyses, enabled us to characterize ancestry-specific genomic regions in different time periods and geographic regions and detect signatures of natural selection. Our research highlights admixture's evolutionary and health implications, focusing on the historical and demographic dynamics that shaped Brazilian genomes. Our results contribute to a deeper understanding of how global haplotypes and admixture patterns resulting from an intricate evolutionary history could affect an admixed population's health. RESULTS: We identified >8 million previously unknown variants, 36,637 of which are putatively deleterious, and elucidated a positive correlation between these deleterious variants and genetic ancestry components. We also showed that the Brazilian population is a tapestry of global haplotypes shaped by nonrandom mating, with the peak of admixture occurring in the 18th and 19th centuries. Multiple or continuous admixture events between Indigenous American, African, and European parental sources have formed Brazilian populations. These processes align with major historical events that have shaped the Brazilian state over the past five centuries. We also identified that, after a prolonged period of sex-biased mating in the initial centuries, a strong pattern of assortative mating has more recently emerged in the Brazilian population, regardless of the region studied. These patterns reveal both the violent dynamics of European colonization and the lasting imprints of this process on contemporary South America. Within the extensive diversity found in Brazil, ancestral-specific genomic regions originating from different populations are unevenly spread across Brazilian regions and historical time frames. This distribution demonstrates the lasting impact of the hundreds of ethnicities that arrived in the country through millions of Europeans and Africans at different times, admixing with and replacing the original Indigenous population. Furthermore, our study identifies several candidate genes that were subject to selection both before and after contact in the Brazilian admixed population. These genes are primarily associated with heightened fertility rates, immune response, and distinctive metabolic traits. CONCLUSION: Our findings underscore the discernible influence of different ancestral backgrounds on Brazilian admixed individuals' health and genetic makeup. We show that this genetic landscape finds its roots in the evolutionary history of Brazilian Indigenous communities and the intricate demographic interplay stemming from both coerced and voluntary historical immigration to Brazil. Brazilian genomic diversity.: A comprehensive study of 2723 high-coverage whole-genome sequences from diverse Brazilian regions reveals >8 million newly identified single-nucleotide variants (SNVs), highlighting Brazil's pronounced genomic diversity, shaped by natural selection, nonrandom mating, and continuous admixture pulses since 1500. These findings underscore the influence of ancestral backgrounds on the health and genetic profile of the Brazilian population, rooted in Indigenous history and diverse immigration waves. [ABSTRACT FROM AUTHOR]