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En este trabajo se evalúa la relación entre la asimetría fluctuante facial (AFF) y los tratamientos hormonales, cirugías maxilofaciales, ortodoncia, traumatismos y malformaciones. En el marco del proyecto CANDELA, se tomaron cinco fotografías faciales de 3162 voluntarios entre los 18 y 85 años. Por fotogrametría se colocaron 34 landmarks o puntos en 3D y mediante el método Procrustes ANOVA se obtuvieron valores individuales de asimetría fluctuante facial. Se realizó una prueba de ANOVA de una vía y la prueba de Welch y Levene para conocer las diferencias entre media y varianza de los valores de asimetría facial y las variables respuesta. También, se caracterizó la variación morfológica del componente asimétrico de la forma facial mediante técnicas multivariadas sobre los grupos que resultaran diferentes significativamente. Las mujeres que reportaron haber recibido algún tipo de tratamiento hormonal mostraron mayores valores de asimetría fluctuante facial respecto al grupo sin tratamiento. Esta asociación se mantuvo una vez removido el efecto de la heterocigosidad (como indicador de la ancestría) y sin interactuar con el resto de covariables incluidas en el análisis. Los cambios morfológicos asociados a este factor se concentran en el mentón, maxilar labio inferior, región perifrontal, región nasal y orejas. Algunos trabajos anteriores dieron cuenta de la posible relación entre la asimetría facial y los niveles de hormonas, pero no hay estudios que sustenten la relación causal o directa entre la asociación aquí planteada. El presente trabajo es una evidencia más de la asociación entre el consumo de hormonas y modificaciones de caracteres faciales en poblaciones urbanas mestizas latinoamericanas., In this work we test for the putative association between facial fluctuating asymmetry (FFA) and hormone treatments, maxillofacial surgery, orthodontics, injuries, and malformations. A protocol of five photographs and photogrammetric reconstruction was implemented to place thirty-four 3D landmarks in 3162 individuals aged between 18 and 85 years, belonging to the CANDELA initiative. A Procrustes ANOVA test was used to obtain individual facial fluctuating asymmetry scores. One way ANOVA, Welch, and Levene tests were conducted to explore the potential differences between mean and variance of the response variables. Our results indicate that women who received some hormonal treatment showed higher fluctuating facial asymmetry scores in relation to the unaffected group, this being persistent once the effects of heterozygosity (genetic ancestry) and further variables had been statistically controlled. The shape changes corresponding to this association are focused on the chin, jaw, lower lip, prefrontal region, nose, and ears. Previous reports suggested a potential relationship between facial asymmetry and hormone levels, but to the best of our knowledge there are no reports indicating the causation underlying the association detected here. This report is one more evidence of the association between hormone intake and facial asymmetric features in urban admixed Latin American populations., Asociación de Antropología Biológica de la República Argentina

We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values, Humans show great diversity in facial appearance and this variation is highly heritable. Here, Andres Ruiz-Linares and colleagues examined facial features in admixed Latin Americans and identify genome-wide associations for 14 facial traits, including four gene loci (RUNX2, GLI3, DCHS2 and PAX1) influencing nose morphology.

We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10−8 to 3 × 10−119), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair., By examining Latin American individuals of mixed European, Native American and African ancestry, Adhikari et al. identify novel loci influencing various features of facial and scalp hair. The study also provides experimental evidence that one of the implicated genes (PRSS53) is expressed in the hair follicle and that the top associated variant alters processing of this enzyme.

Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10−8 to 3 × 10−14). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1., The shape of the pinna varies widely in the general human population but the genetic basis of this variation is unknown. Here Adhikari et al. conduct a genome-wide association study in Latin Americans and discover seven gene regions influencing pinna morphology, including EDAR and TBX15.

It has been proposed that the functional ACTN3*R577X polymorphism might have evolved due to selection in Eurasian human populations. To test this possibility we surveyed all available population-based data for this polymorphism and performed a comprehensive evolutionary analysis of its genetic diversity, in order to assess the action of adaptive and random mechanisms on its variation across human geographical distribution. The derived 577X allele increases in frequency with distance from Africa, reaching the highest frequencies on the American continent. Positive selection, detected by an extended haplotype homozygosisty test, was consistent only with the Eurasian data, but simulations with neutral models could not fully explain the results found in the American continent. It is possible that particularities of Native American population structure could be responsible for the observed allele frequencies, which would have resulted from a complex interaction between selective and random factors.

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry., Author Summary Latin America has a history of extensive mixing between Native Americans and people arriving from Europe and Africa. As a result, individuals in the region have a highly heterogeneous genetic background and show great variation in physical appearance. Latin America offers an excellent opportunity to examine the genetic basis of the differentiation in physical appearance between Africans, Europeans and Native Americans. The region is also an advantageous setting in which to examine the interplay of genetic, physical and social factors in relation to ethnic/racial self-perception. Here we present the most extensive analysis of genetic ancestry, physical diversity and self-perception of ancestry yet conducted in Latin America. We find significant geographic variation in ancestry across the region, this variation being consistent with demographic history and census information. We show that genetic ancestry impacts many aspects of physical appearance. We observe that self-perception is highly influenced by physical appearance, and that variation in physical appearance biases self-perception of ancestry relative to genetically estimated ancestry.

Antisocial and criminal behaviors are multifactorial traits whose interpretation relies on multiple disciplines. Since these interpretations may have social, moral and legal implications, a constant review of the evidence is necessary before any scientific claim is considered as truth. A recent study proposed that men with wider faces relative to facial height (fWHR) are more likely to develop unethical behaviour mediated by a psychological sense of power. This research was based on reports suggesting that sexual dimorphism and selection would be responsible for a correlation between fWHR and aggression. Here we show that 4,960 individuals from 94 modern human populations belonging to a vast array of genetic and cultural contexts do not display significant amounts of fWHR sexual dimorphism. Further analyses using populations with associated ethnographical records as well as samples of male prisoners of the Mexico City Federal Penitentiary condemned by crimes of variable level of inter-personal aggression (homicide, robbery, and minor faults) did not show significant evidence, suggesting that populations/individuals with higher levels of bellicosity, aggressive behaviour, or power-mediated behaviour display greater fWHR. Finally, a regression analysis of fWHR on individual’s fitness showed no significant correlation between this facial trait and reproductive success. Overall, our results suggest that facial attributes are poor predictors of aggressive behaviour, or at least, that sexual selection was weak enough to leave a signal on patterns of between- and within-sex and population facial variation.

Um grande desafio para os geneticistas da atualidade é desvendar as relações que os genes ou regiões gênicas, bem como suas variáveis, têm com determinados fenótipos. Deste modo as abordagens apresentadas neste estudo buscaram ajudar a desvendar a conexão entre alguns destes genes/regiões gênicas com variações morfológicas e metabólicas em populações humanas e em outros mamíferos. Os resultados deste trabalho foram apresentados sob a forma de artigos científicos, sendo que os resultados podem ser resumidos como segue: 1) Hünemeier et al. 2009. TCOF1 T/Ser variant and brachycephaly in dogs. Animal Genetics; 40(3):357-358. Neste trabalho foi demonstrado que o polimorfismo do éxon 4 (C396T, Pro117Ser) do gene TCOF1, está envolvido nos mecanismos de variação morfológica da face, sendo encontrado com mais freqüência em cães braquicéfalos do que meso e dolicocéfalos, porém esta associação não é direta como descrita anteriormente. Foram encontrados cães dolicocéfalos homozigotos para o alelo T/Ser, bem como cães braquicéfalos homozigotos para o alelo C/Pro. Considerando a intricada rede de regulação e expressão deste gene, a mutação por nós estudada pode ser codependente de outras variantes na mesma rede de interação gênica; 2) Hünemeier et al. FGFR1 gene haplotype tag-SNPs, linkage disequilibrium patterns, and their influence in normal craniofacial variation (em preparação para ser submetido para a revista Human Heredity). Neste trabalho dados de variação craniofacial foram obtidos e comparados através de análises uni e multivariadas com polimofismos do gene FGFR1 (N = 333). O alelo rs46470905 C parece estar envolvido na variação normal relativo ao índice cefálico encontrado em populações humanas. Entretanto, claramente outros fatores da rede de desenvolvimento também parem estar envolvidos Os blocos de LD variam em cada grupo populacional investigado, influenciando também a relação de cada background genético com os seus respectivos fenótipos. 3) Hünemeier et al 2010. Population Data Support the Adaptive Nature of HACNS1 Sapiens/Neandertal-Chimpanzee Differences in a Limb Expression Domain. American Journal of Physical Anthropology. No prelo. DOI: 10.1002/ajpa.21378. Neste artigo envolvendo o sequenciamento do enhancer HACNS1 em 194 indivíduos de vários grupos geográficos foi possível demonstrar que a ação da seleção positiva na linhagem Homo foi responsável pela fixação das mutações específicas encontradas nesta região quando comparada com o gênero Pan. A ausência de variação intra-específica no Homo sapiens e no Neandertal reforça o papel funcional do enhancer, mantido inalterado posteriormente pela ação extrema de seleção purificadora. Como discutido no artigo, é possível que o mesmo esteja envolvido na regulação de genes que caracterizam morfologicamente nosso gênero, tais como postura ereta e destreza das mãos 4) Hünemeier et al. Gene-culture Dynamics: An Example Involving Native Americans (em preparação para ser submetido para a revista American Journal of Physical Anthropology). Foi possível com este estudo determinar que o alelo funcional autóctone nativo Americano 230Cys do gene ABCA1 teve uma origem a cerca de 8.268 ± 5.916 anos antes do presente, sendo que o aumento de sua freqüência na América Central/Mesoamérica, poderia estar relacionada com a transição de uma cultura caçadora-coletora para agriculturalista, baseada no cultivo do milho. Este caso seria o primeiro exemplo bem documentado de evolução gene-cultura envolvendo alelo autóctone nativo americano. Este cenário, no entanto, não poderia ser extrapolado para a América do Sul e América do Norte, visto que são duas regiões com distintos padrões culturais e ecológicos. Conjuntamente estes achados permitem sugerir que as relações fenótipogenótipo são influenciadas por diversos fatores biológicos/culturais/ambientais e que a variação existente dentro da espécie humana, é resultado de uma intricada rede de interações genéticas, que atuam em todos os níveis do desenvolvimento. Adicionalmente, as interações desta rede no Homo sapiens sapiens se distingue daquelas de outros mamíferos, em especial pela ação catalisadora de processos derivados justamente da característica que torna nossa espécie singular, a cultura. A major challenge for today geneticists is to unveil the relationships that genes or gene regions, and its variables, have over certain phenotypes. Thus the approaches presented in this study sought to help unravelling the connection between some of these genes / gene regions with metabolic and morphological variations in human populations and other mammals. The results of these works were presented in scientific papers, and the results can be summarized as follows: 1) Hünemeier et al. 2009. TCOF1 T / Ser variant and brachycephaly in dogs. Animal Genetics, 40 (3):357-358. This work demonstrated that the polymorphism of the TCOF1 exon 4 (C396T, Pro117Ser) is involved in the mechanisms of morphological variation of the face, being found most often in brachycephalic dogs than meso-and dolichocephalic dogs. However, this association is not straightforward as previously described. Dolichocephalic dogs were found homozygous for the allele T / Ser, and brachycephalic dogs homozygous for the allele C / Pro. Considering the intricate network of regulation and expression of this gene, the mutation that we studied can be co-dependent on other variants on the same gene network; 2) Hünemeier et al. FGFR1 gene haplotype-tag SNPs, linkage disequilibrium patterns, and their influence in normal craniofacial variation (in preparation for Human Heredity journal). In this paper craniofacial variation data were obtained and compared by univariate and multivariate analyses with polymorphic gene FGFR1 (N = 333). Rs46470905 C allele seems to be involved in the normal range relative to the cephalic index found in human populations However, other factors in the development network also enjoy being involved. LD blocks vary in each population group investigated, also influencing the relationship of each genetic background with their respective phenotypes. 3) Hünemeier et al 2010. Population Data Support the Adaptive Nature of HACNS1 sapiens / Neanderthal-Chimpanzee Differences in the Limb Expression Domain. American Journal of Physical Anthropology. In press. DOI: 10.1002/ajpa.21378. This article involved the sequencing of the enhancer HACNS1 in 194 individuals from several continents. It was possible to demonstrate that the action of positive selection in the Homo lineage was responsible for setting the specific mutations found in this region when compared with the genus Pan. The absence of intra- specific variation in Homo sapiens and Neandertal reinforces the functional role of the enhancer, remaining unchanged after due to extreme action of purifying selection. As discussed in the article, it is possible that it is involved in regulating genes that characterize our genus morphologically, such as upright posture and hands dexterity 4) Hünemeier et al. Gene-culture Dynamics: An Example Involving Native Americans (in preparation for American Journal of Physical Anthropology Journal). It was possible to determine from this study that the functional allele indigenous Native American 230Cys ABCA1 gene had an origin about 8268 ± 5916 years before present, and the increase in its frequency in Central America / Mesoamerica could be related to the transition between the hunter-gatherer to agricultural cultures, the last based on the cultivation of maize. This case would be the first well documented example of geneculture co-evolution involving and indigenous Native American functional allele. This scenario, however, could not be extrapolated to South America and North America, since they are two regions with distinct cultural and ecological standards. Together these findings may suggest that the phenotype-genotype relationships are influenced by several biological / cultural / environmental factors and the variation within the species is the result of an intricate network of genetic interactions, which operate at all levels of development. Additionally, the interactions of this network in Homo sapiens sapiens is distinguished from those of others mammals, in particular by the action of catalytic process derived precisely from the characteristic that makes our species unique, the culture.

Há algum tempo dados genéticos vêm sendo utilizados para inferências quanto à natureza do tráfico de escravos ocorrido no período colonial no Atlântico Sul e sobre a origem dos africanos que chegaram ao Brasil. A utilização de marcadores de linhagem mais específicos, como é o caso do DNA mitocondrial (mtDNA) e da região não-recombinante do cromossomo Y (NRY) pode se constituir em poderoso instrumento para o esclarecimento dessas questões. Este trabalho utilizou esses enfoques através do seqüenciamento da HVS-I do mtDNA (highly variable segment I) e de testes em 30 SNPs (single nucleotide polymorphisms) localizados na região não-recombinante do cromossomo Y, em uma amostra de 133 indivíduos classificados como derivados de africanos (preto e pardo) do estado do Rio Grande do Sul (Porto Alegre e região metropolitana), bem como 144 homens classificados do mesmo modo no estado do Rio de Janeiro (Rio de Janeiro e região metropolitana). Os dados do mtDNA indicaram que 89,5% e 78% das matrilinhagens encontradas, respectivamente, no Rio de Janeiro e em Porto Alegre eram de origem africana. Destas, 69% e 82% eram de origem da África Centro-oeste (região típica de povos que falam línguas Bantus), enquanto que a fração complementar teria uma origem no Oeste africano (não-Bantu). Estes resultados estão de acordo com os registros históricos. Os marcadores do cromossomo Y revelaram que 56% (Rio de Janeiro) e 36% (Porto Alegre) destes cromossomos tinham uma origem africana. No entanto, diferentemente do que aconteceu com o mtDNA, as análises não permitiram discriminar os locais de origem dentro do continente africano. Parece, portanto, haver maior estruturação nos dados obtidos com o mtDNA do que com o cromossomo Y, sugerindo uma maior taxa de migração dos homens do que das mulheres dentro do grande tronco lingüístico Niger-Congo. Porto Alegre e Rio de Janeiro quando comparadas em relação ao mtDNA, não apresentam diferenciação significativa, embora pudessem ser observadas algumas diferenças, em destaque a maior presença de linhagens mitocondriais de origem ameríndia em Porto Alegre (16,4%) do que no Rio de Janeiro (8,5%). Já a diferença entre Porto Alegre e o Rio de Janeiro foi significativa quanto aos dados do cromossomo Y. Especialmente notável, é a presença de cromossomos de origem indígena em Porto Alegre: haplogrupos Q* e Q3*, nas freqüências de 3,5% e 1,7%, respectivamente. Analisando somente os indivíduos tipados tanto para o mtDNA quanto para os marcadores do Y, nota-se que ~ 50% deles nas duas amostras apresentam linhagens mitocondriais e do cromossomo Y de origem africana, enquanto de forma complementar, o número de indivíduos com matrilinhagens africanas e cromossomos Y europeus e/ou asiáticos ou ameríndios foi de ~ 41% e ~ 35% para o Rio de Janeiro e Porto Alegre, respectivamente. As amostras estudadas, portanto, caracterizam-se como sendo amplamente mescladas, apenas metade dos genomas considerados sendo de origem completamente africana. Genetic data have been used for some time now for inferences about the nature of the slave trade that occurred in South Atlantic in the Colonial Period, as well as about the origins of the Africans who arrived in Brazil. The use of lineage-specific markers, like mitochondrial DNA (mtDNA) and those of the non-recombining region of the Y chromosome (NRY), can constitute a powerful tool for elucidation of these questions. This work utilized this approach through sequencing of the mtDNA HVS-I (highly variable segment I), as well by testing 30 SNPs (single nucleotide polymorphisms) located in chromosome Y’s nonrecombining region in a sample of 133 individuals classified as African-derived (black or mulatto) from the state of Rio Grande do Sul (Porto Alegre and metropolitan region), as well as 144 men classified in the same manner in the state of Rio de Janeiro (Rio de Janeiro and metropolitan region). The mtDNA data indicated that 89.5% and 78% of the matrilineages found in Rio de Janeiro and Porto Alegre were of African origin. Of these, respectively, 69% and 82% were of Central-West African origin (region typically of people who speak Bantu languages), while the complementary fraction would have the West African origin (non-Bantu). These results are in accordance with the historical records. The Y chromosome markers revealed that 56% (Rio de Janeiro) and 36% (Porto Alegre) of these chromosomes should have an African origin. But differently of what occurred with the mtDNA results, the analyses did not allow a discrimination of the places of their origin within the African continent. It seems, therefore, that a higher structuration occurs in the mtDNA data as compared to the Y chromosome results, suggesting a higher male in relation to female migration rates within the large Niger-Congo linguistic family. Porto Alegre and Rio de Janeiro do not present significant mtDNA frequency differences, although the Amerindian mtDNA presence is higher in Porto Alegre (16.4%) than Rio de Janeiro (8.5%). On the other hand, Porto Alegre and Rio de Janeiro do show significant differences in the Y chromosome data. Especially notable is the presence of Amerindian chromosomes in Porto Alegre: frequencies of, respectively, 3.5% and 1.7% for haplogroups Q* and Q3*. Considering just the individuals simultaneously typed for mtDNA and the Y chromosome, it is verified that ~50% of then show mtDNA and Y chromosome lineages of African origin, while the number of individuals with African mtDNA but European and/or Asiatic or Amerindian lineages was ~41% for Rio de Janeiro and ~35% for Porto Alegre. The samples studied, therefore, can be characterized as amply admixed, only half of the genomes considered being completely of African origin.

A adaptação humana à radiação ocorre, basicamente, pela seleção em genes relacionados à vitamina D e à pigmentação de pele. O objetivo desse trabalho é avaliar se há sinal de que um conjunto pré-selecionado de genes e variantes comuns nessas duas vias estão coevoluindo em populações nativas americanos que habitam diferentes regiões e que têm distintos hábitos de subsistência e dieta. Então podemos sugerir que, se as populações autóctones americanas estiverem adaptadas a seus respectivos contextos geográficos/ecológicos/culturais, é possível que apresentem distribuição alélica diferencial nesses loci. Para testar a hipótese acima, utilizamos dados de varredura genômica, pré-selecionando SNPs de 16 genes (8 relacionados a vitamina D e 8 a pigmentação) em 333 indivíduos de 33 populações nativas. Com objetivo de testar coadaptação, aplicamos um método de redes que mede interação por meio de um cálculo de desequilíbrio de ligação. Comparamos as frequências alélicas, bem como a frequência de indivíduos com as interações alélicas, entre as categorias populacionais relacionadas à incidência de radiação (altas altitudes vs baixas altitudes e altas latitudes vs baixas latitudes) e a potencial variação da disponibilidade de vitamina D na dieta (agriculturalistas vs caçadores-coletores). Aplicando o teste exato de Fisher com correção FDR, encontramos diferenças estatisticamente significativas em diversos SNPs, bem como em combinações alélicas que sugerem interação. Alguns achados merecem destaque. Por exemplo, entre as categorias altas latitudes e baixas latitudes, detectamos uma variante no gene CYP2R1 (alelo A do rs2060793), que confere mais eficiência à enzima codificada por ele, mais frequente em indivíduos de altas latitudes (e baixa incidência de UV). A maior frequência desse alelo pode ter sido favorecida pela seleção natural devido a necessidade aumentada da eficiência no metabolismo da vitamina D nesse ambiente com menos disponibilidade da vitamina. Em relação à comparação entre as categorias altas e baixas altitudes foi encontrada em maior frequência a ligação entre alelos potencialmente 9 funcionais dos genes CYP24A1 e VDR (alelo C do rs2248359 e alelo G do rs11574143, respectivamente) nas terras altas, o que pode ter sido resultado do relaxamento da pressão de seleção para eficiência no metabolismo desse hormônio em ambientes com alta incidência de radiação UV em populações com a pele relativamente clara. No que diz respeito às diferenças nas práticas de subsistência e hábitos de dieta, um alelo (A do rs4516035) relacionado a maior atividade do VDR pode ter sido selecionado em agriculturalistas para compensar a menor disponibilidade dessa vitamina na alimentação deles. Além disso, identificamos alelos (rs3740164/C e rs750358/T) de diferentes genes (CUBN e OCA2, respectivamente) pertencentes a vias distintas (metabolismo da vitamina D e rota da pigmentação) que podem estar sendo segregados juntos em populações nativas que praticam agricultura por favorecerem adaptativamente os indivíduos nesse contexto em particular. The human adaptation to UV radiation occurs, basically, by selection in genes related to vitamin D and skin pigmentation. The objective of this work is to evaluate if there is a signal that a pre-selected set of genes and common variants in these two pathways are co-evolving in Native American populations that inhabit different regions and that have distinct habits of subsistence and diet. Thus, we can suggest that if Native American populations are adapted to their respective geographic/ecological/cultural contexts, they may have differential allelic distribution at these loci. To test the hypothesis above, we used genomic scanning data, pre-selecting SNPs from 17 genes (8 related to vitamin D and 9 to pigmentation) in 333 individuals from 33 Native American populations. In order to test co-adaptation, we applied a method of networks that measures interaction using linkage disequilibrium (LD) approaches. We compared allele frequencies as well as the frequency their interactions, considering population categories related to UV radiation (high altitudes vs low altitudes and high latitudes vs low latitudes), as well as the potential variation of vitamin D availability in the diet (agriculturalists vs hunter-gatherers). Applying the Fisher exact test with FDR correction, we found statistically significant differences in several SNPs, as well as in allelic combinations, suggesting interaction. Some findings deserve attention. For example, among the high latitudes and low latitudes categories, we detected a variant in the CYP2R1 gene (allele A of rs2060793), which gives more efficiency to the enzyme encoded by it, more frequent in individuals of high latitudes (and low incidence of UV). The higher frequency of this allele may have been favored by natural selection because of the increased need for vitamin D metabolism efficiency in this environment with less vitamin availability. Regarding the comparison between the high and low altitudes categories, the interaction between potentially functional alleles of the genes CYP24A1 and VDR (rs2248359 C allele and G allele of rs11574143, respectively) was found to be more frequent in high altitudes populations, which 11 may have resulted from the relaxation of the selection pressure for efficiency in the metabolism of this hormone in environments with high incidence of UV radiation in populations with relatively clear skin. Concerning differences in subsistence practices and dietary habits, an allele (A of rs4516035) related to increased VDR activity may have been selected in agriculturalists to compensate for the lower availability of this vitamin in their foods. In addition, we identified alleles (rs3740164 / C and rs750358 / T) from different genes (CUBN and OCA2, respectively) belonging to distinct pathways (vitamin D metabolism and route of pigmentation) that may be segregating together in agriculturalists, favoring adaptatively individuals from that context.

Os morcegos da família Phyllostomidae, endêmicos da região Neotropical, apresentam notáveis padrões de diversificação nas formas craniofaciais que são associadas às especializações alimentares. Entretanto, as bases genéticas e do desenvolvimento responsáveis pela geração e manutenção de tais especializações adaptativas são amplamente desconhecidas; não apenas nesta linhagem evolutiva, mas para vertebrados de forma geral. Dentre os diversos genes já investigados e associados à morfologia craniofacial, o RUNX2 apresenta amplo potencial de envolvimento causal na diversificação de formas observadas em morcegos filostomídeos. Repetições in tandem na taxa de aminoácidos Glutamina por Alanina (taxa Q/A), relacionadas à morfologia craniana, foram verificadas em carnívoros, porém, o padrão não se manteve quando analisadas outras linhagens de mamíferos como um todo. Neste contexto, o presente estudo analisa, de forma pioneira, o papel da taxa Q/A na diversificação morfológica craniofacial em uma linhagem específica de mamíferos (morcegos filostomídeos) com particular adaptação (distintas dietas, e.g. carnivoria, frugivoria, insetivoria, nectarivoria, onivoria, sanguinivoria). Utilizou-se a abordagem de associação genótipo-fenótipo através de diferentes métodos estatísticos (e.g. correlação de Pearson e inferência Bayesiana), incluindo ainda a relação entre os hábitos alimentares e os traços genotípicos e fenotípicos como variável latente. As análises foram controladas para a não-independência filogenética dos dados, empregando métodos filogenéticos comparativos. Foram verificadas correlações significativas entre a taxa Q/A e diferentes medidas craniométricas que descrevem as mudanças na morfologia integrativa do crânio, em especial a largura e comprimento da maxila superior. Uma correlação positiva entre o aumento da taxa Q/A e os hábitos de frugivoria e onivoria foi verificada, sugerindo também a existência de interação entre o hábito alimentar e as medidas de comprimento e largura da maxila superior, especialmente para animais frugívoros e onívoros. Phyllostomidae bats, a family endemic to the Neotropics, show remarkable diversification in craniofacial forms that are associated with feed specializations. However, the genetic and developmental bases responsible for the generation and maintenance of such morphological adaptation are largely unknown, not only on this evolutionary lineage, but for vertebrates in general. Among the several genes associated with craniofacial morphology so far, RUNX2 is a putative candidate to underlie diversification of forms found in phyllostomids. Tandem repeats in the rate of Glutamine by Alanine amino acids (Q/A ratio), related to cranial morphology, have been demonstrated in carnivores. However, such pattern was not clear when other mammalian lineages were analyzed as a whole. In this context, the present study examines, for the first time, the role of rate Q/A on craniofacial variation in a specific lineage of mammals (phyllostomids) with marked feed specializations (e.g. carnivorous, frugivorous, insectivorous, nectarivorous, omnivorous, hematophagous). The correlation between genotypes and phenotypic traits were made with different statistical methods (e.g. Pearson correlation and Bayesian inference), including the latent variable of diet as well. Such analysis were controlled for the non-independence phylogenetic effect using phylogenetic comparative methods. Significant correlations were observed between different Q/A rates and cranial measurements, which describes changes in the integrative morphology of the skull, especially the length and width of the upper jaw. In addition, a positive correlation between the increase in Q/A rate and frugivorous/omnivorous diet habits was observed, also suggesting the interaction between feed specializations, length and width of the upper jaw, especially for fruit-eating and omnivores animals.

As populações brasileiras são caracterizadas por seus distintos (e extensos) padrões de mestiçagem. Justamente por apresentarem diferenças na proporção da herança genética africana, ameríndia e européia, é esperado que as conexões entre genótipos e fenótipos complexos como é o caso da cor de pele, olhos e cabelos, por exemplo, não sejam idênticas entre diferentes populações brasileiras, ou entre estas e aquelas encontradas em seus grupos ancestrais. Isto é corroborado pela consistente evidência de que grupos geográficos humanos diferem quanto ao background genético relacionado à pigmentação, refletindo-se, portanto, nas suas populações derivadas. Elucidar este background em amostras miscigenadas como a nossa é de fundamental importância para as áreas médica, evolutiva e forense. Na presente tese buscamos entender o que há de mais recente na literatura científica relacionada com a pigmentação humana, bem como produzir conhecimento de extrema relevância neste contexto em populações brasileiras com diferentes histórias demográficas. Para isto, estudamos o efeito de 18 SNPs com pigmentação da pele, olhos e cabelos na amostra de 563 voluntários brasileiros do consórcio internacional CANDELA (Consórcio para análise da diversidade e evolução latino-americana). Além disso, tentamos estabelecer um método de predição de fenótipos de pigmentação com a possível aplicação em genética forense e evolução humana. Na análise de associação dos 18 SNPs com fenótipos de pigmentação, observamos 3 (três) marcadores genéticos (HERC2rs1129038, SLC24A5rs1426654 e SLC45A2rs16891982) consistentemente associados com cor da pele, olhos e cabelos, nas distintas populações brasileiras investigadas. Este é o primeiro passo para compreender melhor o contexto biológico da produção de melanina e entender as relações genótipofenótipo da pigmentação em populações miscigenadas. Com a compreensão dos marcadores genéticos relacionados com pigmentação e também com o aperfeiçoamento do método de predição de fenótipos de pigmentação desenvolvido no presente trabalho, é possível dar o primeiro passo para a criação de uma metodologia de predição de fenótipos de cor da pele, olhos e cabelos em populações com histórias demográficas miscigenadas como a nossa, com possível aplicação nas áreas forense, médica e evolutiva. Brazilian populations are characterized by their distinct (and extensive) admixture patterns. Precisely because there are differences in the proportion of African, Amerindian and European genetic heritage, it is expected that the connections between genotypes and complex phenotypes such as skin, eyes and hair color, are not identical among different Brazilian populations, or between these and those found in their ancestral groups. This is corroborated by consistent evidence that human geographic groups differ in genetic background related to pigmentation, reflecting thus in the respectives populations derived. Elucidating this background in admixed samples such as ours is of fundamental importance to the medical, forensic and evolutionary fields. In this thesis we seek to understand what is latest in the scientific literature related to human pigmentation, as well as producing knowledge extremely relevant in this context in Brazilian populations with different demographic histories. For this, we studied the effect of 18 SNPs with pigmentation of the skin, eyes and hair in a sample of 563 Brazilian volunteers of the international consortium called CANDELA (Consortium for the analysis of the diversity and evolution of Latin America). Also, we try to establish a method for predicting pigmentation phenotypes with possible application in forensic genetics and human evolution. In association analysis of 18 SNPs with pigmentation phenotypes, we observed 3 (three) genetic markers (HERC2rs1129038, SLC24A5rs1426654 and SLC45A2rs16891982) consistently associated with skin, eye and hair color, in distinct Brazilian populations investigated. This is the first step to better understand the biological context of the production of melanin and know the connexions between genotype-phenotype of the pigmentation in admixed populations. With the understanding of the genetic markers related to pigmentation as well as with the improvement of the method of predicting phenotypes developed in the present work, it is possible to take the first step toward establishing a methodology for predicting phenotypes of skin, eye and hair color in populations with demographic histories like ours, with possible application in forensic, medical and evolutionary fields.