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CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior The inclusion of human diversity in genetic studies contributes not only to a better understanding of our history but also to solving biomedical issues such as disease susceptibility, response to medical treatments and elucidation of complex traits. Geneticists have known for more than a decade that focusing on people of European ancestry exacerbates health disparities, and genetic advances can not be applied to those who need it most. Thus, this thesis presents works that contribute to changing this scenario, seeking to increase the visibility of the genetic richness that exists beyond populations of European ancestry. Here, I present research findings that include admixed and non-admixed populations with diverse ancestries, from South American natives to Africans and Asians. The first chapter is a mini-review of the history of humanity on the American continent, told by the genetics of modern and ancient populations, from the arrival of the first humans to the process of admixture, where we also present complementary discussions about the updates of the discoveries made since the publication of this article in 2020. In chapter 2, we present an article published by my group that solves important questions in the Andean and Amazon genetic history, through methods of population genetics. In chapter 3, I devote myself to the methods of scanning these adaptive signatures and create a multi-methodological pipeline for the study of natural selection to minimize the chance of obtaining false positives. Chapter 4 is an important addition to genetically neglected populations and would be a complementary part of our chapter 1, where we applied advances with polygenic risk scores to admixed populations such as the Brazilian. Exploring the diversity of human genetics is not only important for neglected populations, but it is also essential to increase the capacity to make new discoveries. Thus, in the attachments, we present five articles exemplifying how the genomic mosaic of non-European populations is a rich source of information from different perspectives, including medical, historical and evolutionary aspects. The work presented here shows in different ways how the effort to generate data from underrepresented populations makes important contributions to science. A inclusão da diversidade humana nos estudos genéticos contribui não apenas para a melhor compreensão da nossa história, mas tambem para resolver questões biomédicas, como suscetibilidade a doenças, resposta a tratamentos médicos e elucidação de fenótipos complexos. Geneticistas sabem há mais de uma década, que o foco em pessoas de ancestralidade europeia agrava as disparidades de acesso a saúde por parte das populações globais, e os avanços genéticos não são levados a quem mais precisa. Assim, esta tese apresenta trabalhos que contribuem para mudar esse cenário, buscando aumentar a visibilidade da riqueza genética que existe além das populações de ancestralidade europeia. Aqui, apresento resultados de pesquisas que incluem populações miscigenadas e não-miscigenadas com ancestralidades diversas, desde nativos sulamericanos, até africanos e asiáticos. O primeiro capítulo é uma mini revisão da história da humanidade no continente americano, contada pela genética de populações atuais e antigas, desde a chegada dos primeiros seres humanos até o processo de miscigenação, onde tambem apresento discussões complementares sobre às atualizações das descobertas feitas desde a publicação desse artigo em 2020. No capitulo 2, apresento um artigo publicado pelo meu grupo que resolve questões importantes da história genética andina e amazônica, por meio de métodos de genética de populações. No capitulo 3 me aprofundo nos métodos de varredura dessas assinaturas adaptativas e crio um pipeline de estudo de seleção natural multi-metodológico para diminuir ao maximo a chance de se obter falsos-positivos. O Capitulo 4 é uma adição importante para às populações geneticamente negligenciadas e seria uma parte complementar ao nosso capitulo 1, onde eu aplico os avanços com scores poligenicos de riscos às populaçoes miscigenadas, como a Brasileira. Explorar a diversidade da genética humana não é importante apenas para as populações negligenciadas, mas também é essencial para aumentar a capacidade de fazer novas descobertas. Assim, apresento nos anexos, cinco artigos exemplificando como o mosaico genômico de populações não europeias é uma rica fonte de informações de diferentes perspectivas, incluindo aspectos médicos, históricos e evolutivos. O trabalho aqui apresentado mostra de diversas formas como o esforço de geração de dados a partir de populações sub-representadas traz importantes contribuições para a ciência.

The gray-headed tody-flycatcher Todirostrum poliocephalum is a passerine endemic to the Atlantic Forest of Brazil. We describe the nest and nesting behaviour of this species and investigate...

Hair colour is a polygenic phenotype that results from differences in the amount and ratio of melanins located in the hair bulb. Genome-wide association studies (GWAS) have identified many loci involved in the pigmentation pathway affecting hair colour. However, most of the associated loci overlap non-protein coding regions and many of the molecular mechanisms underlying pigmentation variation are still not understood. Here, we conduct GWAS meta-analyses of hair colour in a Canadian cohort of 12,741 individuals of European ancestry. By performing fine-mapping analyses we identify candidate causal variants in pigmentation loci associated with blonde, red and brown hair colour. Additionally, we observe colocalization of several GWAS hits with expression and methylation quantitative trait loci (QTLs) of cultured melanocytes. Finally, transcriptome-wide association studies (TWAS) further nominate the expression of EDNRB and CDK10 as significantly associated with hair colour. Our results provide insights on the mechanisms regulating pigmentation biology in humans., Frida Lona-Durazo et al. perform a GWAS of human hair colour in a Canadian population cohort collected across multiple provinces. By combining these results with transcriptomic and methylation data, the authors provide further insight into the underlying biology of hair colour.

Focusing on literature published in 2018-2020, we review inferences about: (i) how ancient DNA is contributing to clarify the peopling of the Americas and the dispersal of its first inhabitants, (ii) how the interplay between environmental diversity and culture has influenced the genetic structure and adaptation of Andean and Amazon populations, (iii) how genetics has contributed to our understanding of the Pre-Columbian Tupi expansion in Eastern South America, (iv) the subcontinental origins and dynamics of Post-Columbian admixture in the Americas, and finally, (v) episodes of adaptive natural selection in the American continent, particularly in the high altitudes of the Andes.

Western South America was one of the worldwide cradles of civilization. The well known Inca Empire was the tip of the iceberg of a cultural and biological evolutionary process that started 14-11 thousand years ago. Genetic data from 18 Peruvian populations reveal that: (1) The between-population homogenization of the central-southern Andes and its differentiation with respect to Amazonian populations of similar latitudes do not extend northward. Instead, longitudinal gene flow between the northern coast of Peru, Andes and Amazonia accompanied cultural and socioeconomic interactions revealed by archeological studies. This pattern recapitulates the environmental and cultural differentiation between the fertile north, where altitudes are lower; and the arid south, where the Andes are higher, acting as a genetic barrier between the sharply different environments of the Andes and Amazonia (2). The genetic homogenization between the populations of the arid Andes is not only due to migration during the Inca Empire or the subsequent colonial period. It started at least during the earlier expansion of the pre-Inca Wari Empire (600-1000 YBP) (3) This demographic history allowed for cases of positive natural selection in the high and arid Andes vs. the low Amazon tropical forest: in the Andes, HAND2-AS1 (heart and neural crest derivatives expressed 2 antisense RNA1, related with cardiovascular function) and DUOX2 (dual oxidase 2, related to thyroid function and innate immunity) genes; in the Amazon, the gene encoding for the CD45 protein, essential for antigen recognition by T/B lymphocytes in viral-host interaction, consistent with the host-virus arms race hypothesis.

The gray-headed tody-flycatcher Todirostrum poliocephalum is a passerine endemic to the Atlantic Forest of Brazil. We describe the nest and nesting behaviour of this species and investigate geographical variation in breeding traits in the genus using data from the literature, museum collections, and citizen science projects. We located 21 nests of the gray-headed tody-flycatcher, 13 of which we monitored. Nest height above the ground averaged 3.3 ± 3.4 m (n = 21). Nests were built over a 16.8 ± 5.6-day period (n = 6) by both adults. Clutch sizes ranged from two to three eggs, with a mean of 2.9 ± 0.3 eggs (n = 10). Eggs measured 16.6 ± 0.5 × 12.0 ± 0.5 mm (n = 23) and weighed 1.1 ± 0.1 g (n = 19). Mean incubation period was 17 days (n = 3) and mean nestling period was 15.5 days (n = 2). Apparent reproductive success was 30.8%, with predation being the primary cause of nest failure (46.1%). Mayfield’s reproductive success was 25.9%, and daily survival rates for eggs and nestlings were 0.957 and 0.971, respectively. Clutch sizes increased with latitude, but temperature and precipitation seasonality had very low importance in explaining clutch size variation.