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1.
Sci Adv ; 7(6)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33547071

RESUMO

To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice.

2.
Am J Med Genet C Semin Med Genet ; 184(4): 1060-1077, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33325159

RESUMO

We carried out an exhaustive review regarding human skin color variation and how much it may be related to vitamin D metabolism and other photosensitive molecules. We discuss evolutionary contexts that modulate this variability and hypotheses postulated to explain them; for example, a small amount of melanin in the skin facilitates vitamin D production, making it advantageous to have fair skin in an environment with little radiation incidence. In contrast, more melanin protects folate from degradation in an environment with a high incidence of radiation. Some Native American populations have a skin color at odds with what would be expected for the amount of radiation in the environment in which they live, a finding challenging the so-called "vitamin D-folate hypothesis." Since food is also a source of vitamin D, dietary habits should also be considered. Here we argue that a gene network approach provides tools to explain this phenomenon since it indicates potential alleles co-evolving in a compensatory way. We identified alleles of the vitamin D metabolism and pigmentation pathways segregated together, but in different proportions, in agriculturalists and hunter-gatherers. Finally, we highlight how an evolutionary approach can be useful to understand current topics of medical interest.

3.
Mol Biol Evol ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32986821

RESUMO

The origin of nervous systems is a main theme in biology and its mechanisms are largely underlied by synaptic neurotransmission. One problem to explain synapse establishment is that synaptic orthologs are present in multiple aneural organisms. We questioned how the interactions among these elements evolved and to what extent it relates to our understanding of the nervous systems complexity. We identified the human neurotransmission gene network based on genes present in GABAergic, glutamatergic, serotonergic, dopaminergic, and cholinergic systems. The network comprises 321 human genes, 83 of which act exclusively in the nervous system. We reconstructed the evolutionary scenario of synapse emergence by looking for synaptic orthologs in 476 eukaryotes. The Human-Cnidaria common ancestor displayed a massive emergence of neuroexclusive genes, mainly ionotropic receptors, which might have been crucial to the evolution of synapses. Very few synaptic genes had their origin after the Human-Cnidaria common ancestor. We also identified a higher abundance of synaptic proteins in vertebrates, which suggests an increase in the synaptic network complexity of those organisms.

4.
Sci Rep ; 10(1): 13706, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32792643

RESUMO

Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10-6). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10-10). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America.

5.
Genet Mol Biol ; 43(2): e20200104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520981

RESUMO

The recent emergence of SARS-CoV-2 is responsible for the current pandemic of COVID-19, which uses the human membrane protein ACE2 as a gateway to host-cell infection. We performed a comparative genomic analysis of 70 ACE2 placental mammal orthologues to identify variations and contribute to the understanding of evolutionary dynamics behind this successful adaptation to infect humans. Our results reveal that 4% of the ACE2 sites are under positive selection, all located in the catalytic domain, suggesting possibly taxon-specific adaptations related to the ACE2 function, such as cardiovascular physiology. Considering all variable sites, we selected 30 of them located at the critical ACE2 binding sites to the SARS-CoV-like viruses for analysis in more detail. Our results reveal a relatively high diversity of ACE2 between placental mammal species, while showing no polymorphism within human populations, at least considering the 30 inter-species variable sites. A perfect scenario for natural selection favored this opportunistic new coronavirus in its trajectory of infecting humans. We suggest that SARS-CoV-2 became a specialist coronavirus for human hosts. Differences in the rate of infection and mortality could be related to the innate immune responses, other unknown genetic factors, as well as non-biological factors.

6.
Infect Genet Evol ; 84: 104364, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32422351

RESUMO

Despite worldwide research efforts since 2015, Zika virus infection and its consequences are not fully understood yet. Nowadays, it is known that microcephaly is only one of the possible outcomes of being infected by ZIKV during the early stages of life. Musashi 1 (MSI1) is an RNA-binding protein that is involved in neurodevelopmental processes. Also, ZIKV genome (a single-stranded positive-sense RNA) uses MSI1 for its replication. Here we perform an evolutionary analysis of MSI1 coding sequence and their orthologs in vertebrate species. We added original sequencing data from selected regions of interest (RNA-binding domains-RBDs of MSI1) of sixteen Platyrrhini (or New World monkeys), known to have high evolutionary rates. The Musashi family (MF) includes MSI2, TARDBP, DAZAP1, HNRNPD, HNRNPDL, and HNRNPAB, which do not interact with the virus but are critical RNA-binding proteins that act on many regulatory processes ubiquitously. We found that all sixteen primate species have the RBD1 of MSI1 conserved. While the general code sequences of MF genes are under purifying selection, the evolution of regulatory mechanisms, especially alternative splicing, seems to be a frequent phenomenon in these genes. Different isoforms differ in the N-terminal region and it affects protein size. Existing MSI1 isoforms probably diverge in their binding affinity, the kinetics of interaction, and other aspects when in the MSI1-ZIKV complex. It is a signal that some RBD-containing MSI1 isoforms can be incompatible to ZIKV binding and replication. Consequently, the chance of ZIKV successfully infecting host cells could also be associated with alternative splicing and expression of ZIKV-compatible MSI1 isoforms in both inter and intraspecific levels.

7.
Preprint em Inglês | SciELO Preprints | ID: pps-34

RESUMO

The recent emergence of SARS-CoV-2 is responsible for the current pandemic of COVID-19, which uses the human membrane protein ACE2 as a gateway to the host-cell infection. We perform comparative genomic analysis of 70 ACE2 placental mammal orthologues to identify variations and contribute to the understanding of evolutionary dynamics behind this successful adaptation to infect humans. Our results reveal that 4% of the ACE2 sites are under positive selection, all located in the catalytic domain, suggesting possibly taxon-specific adaptations related to the ACE2 function, such as cardiovascular physiology. Considering all variable sites, we selected 30 of them located at the critical ACE2 binding sites to the SARS-CoV-like viruses to analyze in more detail. Our results reveal a relatively high diversity of ACE2 between placental mammal species while showing no polymorphism within human populations, at least considering the 30 inter-species variable sites. A perfect scenario for natural selection favored this opportunistic new coronavirus in its trajectory of infecting humans. We suggest that SARS-CoV-2 became a specialist coronavirus for human hosts. Differences in the rate of infection and mortality could be related to the innate immune responses, other unknown genetic factors, as well as non-biological factors.

8.
Mol Biol Evol ; 37(6): 1647-1656, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32128591

RESUMO

The Transatlantic Slave Trade transported more than 9 million Africans to the Americas between the early 16th and the mid-19th centuries. We performed a genome-wide analysis using 6,267 individuals from 25 populations to infer how different African groups contributed to North-, South-American, and Caribbean populations, in the context of geographic and geopolitical factors, and compared genetic data with demographic history records of the Transatlantic Slave Trade. We observed that West-Central Africa and Western Africa-associated ancestry clusters are more prevalent in northern latitudes of the Americas, whereas the South/East Africa-associated ancestry cluster is more prevalent in southern latitudes of the Americas. This pattern results from geographic and geopolitical factors leading to population differentiation. However, there is a substantial decrease in the between-population differentiation of the African gene pool within the Americas, when compared with the regions of origin from Africa, underscoring the importance of historical factors favoring admixture between individuals with different African origins in the New World. This between-population homogenization in the Americas is consistent with the excess of West-Central Africa ancestry (the most prevalent in the Americas) in the United States and Southeast-Brazil, with respect to historical-demography expectations. We also inferred that in most of the Americas, intercontinental admixture intensification occurred between 1750 and 1850, which correlates strongly with the peak of arrivals from Africa. This study contributes with a population genetics perspective to the ongoing social, cultural, and political debate regarding ancestry, admixture, and the mestizaje process in the Americas.

9.
Proc Natl Acad Sci U S A ; 117(5): 2372-2377, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31932419

RESUMO

In the 15th century, ∼900,000 Native Americans, mostly Tupí speakers, lived on the Brazilian coast. By the end of the 18th century, the coastal native populations were declared extinct. The Tupí arrived on the east coast after leaving the Amazonian basin ∼2,000 y before present; however, there is no consensus on how this migration occurred: toward the northern Amazon and then directly to the Atlantic coast, or heading south into the continent and then migrating to the coast. Here we leveraged genomic data from one of the last remaining putative representatives of the Tupí coastal branch, a small, admixed, self-reported Tupiniquim community, as well as data of a Guaraní Mbyá native population from Southern Brazil and of three other native populations from the Amazonian region. We demonstrated that the Tupiniquim Native American ancestry is not related to any extant Brazilian Native American population already studied, and thus they could be considered the only living representatives of the extinct Tupí branch that used to settle the Atlantic Coast of Brazil. Furthermore, these data show evidence of a direct migration from Amazon to the Northeast Coast in pre-Columbian time, giving rise to the Tupí Coastal populations, and a single distinct migration southward that originated the Guaraní people from Brazil and Paraguay. This study elucidates the population dynamics and diversification of the Brazilian natives at a genomic level, which was made possible by recovering data from the Brazilian coastal population through the genomes of mestizo individuals.


Assuntos
Genoma Humano/genética , Índios Sul-Americanos/genética , Dinâmica Populacional , Brasil , Variação Genética , Genômica , Humanos , Densidade Demográfica
10.
Elife ; 82019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31763980

RESUMO

The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited, despite the relevance for various fields. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching study-wide suggestive association (p < 5 × 10-8), among which 17 were previously unreported. A follow-up multi-ethnic study in additional 7917 individuals confirmed 10 loci including six unreported ones (padjusted < 2.1 × 10-3). A global map of derived polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis-regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies.


Assuntos
Face/anatomia & histologia , Loci Gênicos/genética , Desenvolvimento Maxilofacial/genética , Fenótipo , Adolescente , Adulto , Pontos de Referência Anatômicos , Padronização Corporal/genética , Criança , Pré-Escolar , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Ontologia Genética , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Adulto Jovem
11.
Genome Biol Evol ; 11(9): 2593-2604, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31328768

RESUMO

After the colonization of the Americas by Europeans and the consequent Trans-Atlantic Slave Trade, most Native American populations in eastern Brazil disappeared or went through an admixture process that configured a population composed of three main genetic components: the European, the sub-Saharan African, and the Native American. The study of the Native American genetic history is challenged by the lack of availability of genome-wide samples from Native American populations, the technical difficulties to develop ancient DNA studies, and the low proportions of the Native American component in the admixed Brazilian populations (on average 7%). We analyzed genome-wide data of 5,825 individuals from three locations of eastern Brazil: Salvador (North-East), Bambui (South-East), and Pelotas (South) and we reconstructed populations that emulate the Native American groups that were living in the 16th century around the sampling locations. This genetic reconstruction was performed after local ancestry analysis of the admixed Brazilian populations, through the rearrangement of the Native American haplotypes into reconstructed individuals with full Native American ancestry (51 reconstructed individuals in Salvador, 45 in Bambui, and 197 in Pelotas). We compared the reconstructed populations with nonadmixed Native American populations from other regions of Brazil through haplotype-based methods. Our results reveal a population structure shaped by the dichotomy of Tupi-/Jê-speaking ancestry related groups. We also show evidence of a decrease of the diversity of nonadmixed Native American groups after the European contact, in contrast with the reconstructed populations, suggesting a reservoir of the Native American genetic diversity within the admixed Brazilian population.


Assuntos
Índios Sul-Americanos/genética , Brasil , Variação Genética , Genoma Humano , Geografia , Haplótipos , Humanos , Densidade Demográfica
12.
Am J Primatol ; 81(8): e23028, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31318063

RESUMO

Platyrrhini (New World monkeys, NWm) are a group of primates characterized by behavioral and reproductive traits that are otherwise uncommon among primates, including social monogamy, direct paternal care, and twin births. As a consequence, the study of Platyrrhine primates is an invaluable tool for the discovery of the genetic repertoire underlying these taxon-specific traits. Recently, high conservation of vasopressin (AVP) sequence, in contrast with high variability of oxytocin (OXT), has been described in NWm. AVP and OXT functions are possible due to interaction with their receptors: AVPR1a, AVPR1b, AVPR2, and OXTR; and the variability in this system is associated with the traits mentioned above. Understanding the variability in the receptors is thus fundamental to understand the function and evolution of the system as a whole. Here we describe the variability of AVPR1b coding region in 20 NWm species, which is well-known to influence behavioral traits such as aggression, anxiety, and stress control in placental mammals. Our results indicate that 4% of AVPR1b sites may be under positive selection and a significant number of sites under relaxed selective constraint. Considering the known role of AVPR1b, we suggest that some of the changes described here for the Platyrrhini may be a part of the genetic repertoire connected with the complex network of neuroendocrine mechanisms of AVP-OXT system in the modulation of the HPA axis. Thus, these changes may have promoted the emergence of social behaviors such as direct paternal care in socially monogamous species that are also characterized by small body size and twin births.


Assuntos
Evolução Molecular , Platirrinos/genética , Receptores de Vasopressinas/genética , Comportamento Social , Animais , Variação Genética , Tamanho da Ninhada de Vivíparos/genética , Comportamento Paterno , Fenótipo , Comportamento Sexual Animal
13.
Am J Hum Biol ; 31(3): e23243, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31016798

RESUMO

OBJECTIVES: The major aim of this article was to estimate the demographic impact of European arrival and colonization over Native American populations from southern Brazil and Uruguay. We also compared the mitochondrial DNA (mtDNA) genetic diversity, structure, and demography of Native American lineages present in current indigenous (Natives) and nonindigenous admixed (Admixed) populations to estimate the effective population size (Ne ) of contemporary and ancestral (pre-Columbian) Native American populations. METHODS: We retrieved published mtDNA sequences from Native (n = 396) and Admixed (n = 309) populations from southern Brazil, Uruguay, and surrounding areas. We conducted genetic diversity, structure, and demographic analyses. Finally, we used Approximate Bayesian Computation to estimate the Ne for current Native, Admixed, and pre-Columbian Native American populations. RESULTS: We found higher Native American mtDNA genetic diversity in admixed rather than in indigenous populations (131/309 vs 27/396 different haplotypes, respectively). Only Admixed populations maintained ancient signals of the Native American population expansion approximately 14 to 17 kya, which have decayed in Natives. Our Ne estimates suggest that Natives represent only 0.33% (0.18%-1.19%) of the Ne for ancestral pre-Columbian indigenous populations. CONCLUSIONS: Admixed populations represent an important genetic reservoir of Native American lineages, many of which are extinct in contemporary indigenous populations. In addition, the Native American lineages present in Admixed populations retain part of the past demographic history of Native Americans. The intensity of the reduction is congruent with historical accounts of strong indigenous depopulation during the colonization process.


Assuntos
Colonialismo/história , DNA Mitocondrial/análise , Grupo com Ancestrais do Continente Europeu/genética , Índios Sul-Americanos/genética , Densidade Demográfica , Teorema de Bayes , Brasil , História do Século XVI , História do Século XVII , Humanos , Modelos Biológicos , Uruguai
14.
Nat Commun ; 10(1): 358, 2019 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-30664655

RESUMO

We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.


Assuntos
Epistasia Genética , Cor de Olho/genética , Genoma Humano , Locos de Características Quantitativas , Pigmentação da Pele/genética , Alelos , Grupo com Ancestrais do Continente Asiático , Evolução Biológica , Grupos Étnicos , Grupo com Ancestrais do Continente Europeu , Feminino , Expressão Gênica , Frequência do Gene , Genética Populacional , Estudo de Associação Genômica Ampla , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , América Latina , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Polimorfismo de Nucleotídeo Único , Receptor de Glutamato Metabotrópico 5/genética , Ubiquitina-Proteína Ligases
15.
Am J Phys Anthropol ; 168(3): 438-447, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30582632

RESUMO

OBJECTIVES: To investigate the variation in dental nonmetric traits and to evaluate the utility of this variation for inferring genetic ancestry proportions in a sample of admixed Latin Americans. MATERIALS AND METHODS: We characterized a sample from Colombia (N = 477) for 34 dental traits and obtained estimates of individual Native American, European, and African ancestry using genome-wide SNP data. We tested for correlation between dental traits, genetic ancestry, age, and sex. We carried out a biodistance analysis between the Colombian sample and reference continental population samples using the mean measure of divergence statistic calculated from dental trait frequencies. We evaluated the inference of genetic ancestry from dental traits using a regression approach (with 10-fold cross-validation) as well as by testing the correlation between estimates of ancestry obtained from genetic and dental data. RESULTS: Latin Americans show intermediate dental trait frequencies when compared to Native Americans, Europeans, and Africans. Significant correlations were observed for several dental traits, genetic ancestry, age, and sex. The biodistance analysis displayed a closer relationship of Colombians to Europeans than to Native Americans and Africans. Mean ancestry estimates obtained from the dental data are similar to the genetic estimates (Native American: 32% vs. 28%, European: 59% vs. 63%, and African: 9% vs. 9%, respectively). However, dental features provided low predictive power for genetic ancestry of individuals in both approaches tested (R2 < 5% for all genetic ancestries across methods). DISCUSSION: The frequency of dental traits in Latin Americans reflects their admixed Native American, European and African ancestry and can provide reasonable average estimates of genetic ancestry. However, the accuracy of individual genetic ancestry estimates is relatively low, probably influenced by the continental differentiation of dental traits, their genetic architecture, and the distribution of genetic ancestry in the individuals examined.


Assuntos
Grupos de Populações Continentais , Hispano-Americanos/genética , Dente/anatomia & histologia , Adolescente , Adulto , Antropologia Física , Grupos de Populações Continentais/genética , Grupos de Populações Continentais/estatística & dados numéricos , Feminino , Genética Populacional , Hispano-Americanos/estatística & dados numéricos , Humanos , Masculino , Fotografia Dentária , Adulto Jovem
16.
Int J Cardiol ; 279: 168-173, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30305239

RESUMO

BACKGROUND: Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there are few GWAS in Latino populations, and the role of SUA-associated single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population. METHODS: We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD. RESULTS: Only two loci were associated with SUA levels: SLC2A9 (ß = -0.47 mg/dl, P = 1.57 × 10-42 for lead SNP rs7678287) and ABCG2 (ß = 0.23 mg/dl, P = 2.42 × 10-10 for lead SNP rs2231142). No significant interaction between SLC2A9 rs7678287 and ABCG2 rs2231142 genotypes and obesity was observed. However, a significant ABCG2 rs2231142 genotype*sex interaction (P = 0.001) was observed in adults but not in children. Although SUA levels were associated with premature CAD, metabolic syndrome and decreased glomerular filtration rate (eGFR), only ABCG2 rs2231142 was associated with decreased eGFR in the premature CAD group. CONCLUSIONS: SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABCG2) did not support a causal role of elevated SUA levels for premature CAD.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único/genética , Ácido Úrico/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Criança , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Masculino , Análise da Randomização Mendeliana/métodos , México/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem
17.
Nat Commun ; 9(1): 5388, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30568240

RESUMO

Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample.


Assuntos
Migração Humana , Índios Norte-Americanos/genética , Índios Sul-Americanos/genética , Haplótipos , Humanos , México , Nariz/anatomia & histologia , América do Sul
18.
PLoS Genet ; 14(9): e1007640, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30248107

RESUMO

Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10(-10)) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10(-8)). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10(-11)) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure.


Assuntos
Sobrancelhas/crescimento & desenvolvimento , Loci Gênicos/genética , Fenótipo , Sistemas CRISPR-Cas/genética , Cromossomos Humanos/genética , Fatores de Transcrição Forkhead/genética , Edição de Genes , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição SOXB1/genética , Seleção Genética
19.
Sci Rep ; 8(1): 12733, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-30143708

RESUMO

The Andean Altiplano has been occupied continuously since the late Pleistocene, ~12,000 years ago, which places the Andean natives as one of the most ancient populations living at high altitudes. In the present study, we analyzed genomic data from Native Americans living a long-time at Andean high altitude and at Amazonia and Mesoamerica lowland areas. We have identified three new candidate genes - SP100, DUOX2 and CLC - with evidence of positive selection for altitude adaptation in Andeans. These genes are involved in the TP53 pathway and are related to physiological routes important for high-altitude hypoxia response, such as those linked to increased angiogenesis, skeletal muscle adaptations, and immune functions at the fetus-maternal interface. Our results, combined with other studies, showed that Andeans have adapted to the Altiplano in different ways and using distinct molecular strategies as compared to those of other natives living at high altitudes.


Assuntos
Adaptação Fisiológica/genética , Altitude , Grupo com Ancestrais Nativos do Continente Americano/genética , Loci Gênicos , Seleção Genética , Alelos , Genética Populacional , Geografia , Haplótipos/genética , Homozigoto , Humanos , Polimorfismo de Nucleotídeo Único/genética , América do Sul
20.
J Evol Biol ; 31(8): 1180-1192, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29943391

RESUMO

Traits that undergo massive natural selection pressure, with multiple events of positive selection, are hard to find. Social behaviour, in social animals, is crucial for survival, and genetic networks involved in behaviour, such as those of serotonin (5-HT) and other neurotransmitters, must be the target of natural selection. Here, we used molecular analyses to search for signals of positive selection in the 5-HT system and found such signals in the M3-M4 intracellular domain of the 5-HT3A serotonin receptor subunit (HTR3A) in primates. We detected four amino acid sites with signs of putatively positive selection (398, 403, 432 and 416); the first three showed indications of being selected in New World monkeys (NWM, Platyrrhini), specifically in the Callitrichinae branch. Additionally, we searched for associations of these amino acid variants with social behavioural traits (i.e. sex-biased dispersal, dominance and social monogamy) using classical and Bayesian methods, and found statistically significant associations for unbiased sex dispersal (398L and 416S), unbiased sex dominance (416S) and social monogamy (416S), as well as significant positive correlation between female dispersal and 403G. Furthermore, we found putatively functional protein motifs determined by three selected sites, of which we highlight a ligand motif to GSK3 in the 416S variant, appearing only in Platyrrhini. 5-HT, 5-HT3A receptor and GSK3 are part of a network that participates in neurodevelopment and regulates behaviour, among other functions. We suggest that these genetic variations, together with those found in other neurotransmitter systems, must contribute to adaptive behaviours and consequently to fitness in NWMs.


Assuntos
Comportamento Animal/fisiologia , Platirrinos/genética , Platirrinos/fisiologia , Seleção Genética , Serotonina/metabolismo , Animais , Evolução Molecular , Regulação da Expressão Gênica/fisiologia , Filogenia , Serotonina/genética
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