Searching for ancient balanced polymorphisms shared between Neanderthals and Modern Humans

Abstract Hominin evolution is characterized by adaptive solutions often rooted in behavioral and cognitive changes. If balancing selection had an important and long-lasting impact on the evolution of these traits, it can be hypothesized that genes associated with them should carry an excess of shared polymorphisms (trans- SNPs) across recent Homo species. In this study, we investigate the role of balancing selection in human evolution using available exomes from modern (Homo sapiens) and archaic humans (H. neanderthalensis and Denisovan) for an excess of trans-SNP in two gene sets: one associated with the immune system (IMMS) and another one with behavioral system (BEHS). We identified a significant excess of trans-SNPs in IMMS (N=547), of which six of these located within genes previously associated with schizophrenia. No excess of trans-SNPs was found in BEHS, but five genes in this system harbor potential signals for balancing selection and are associated with psychiatric or neurodevelopmental disorders. Our approach evidenced recent Homo trans-SNPs that have been previously implicated in psychiatric diseases such as schizophrenia, suggesting that a genetic repertoire common to the immune and behavioral systems could have been maintained by balancing selection starting before the split between archaic and modern humans.

Oxytocin and arginine vasopressin systems in the domestication process

Abstract Domestication is of unquestionable importance to the technological revolution that has given rise to modern human societies. In this study, we analyzed the DNA and protein sequences of six genes of the oxytocin and arginine vasopressin systems (OXT-OXTR; AVP-AVPR1a, AVPR1b and AVPR2) in 40 placental mammals. These systems play an important role in the control of physiology and behavior. According to our analyses, neutrality does not explain the pattern of molecular evolution found in some of these genes. We observed specific sites under positive selection in AVPR1b (ω = 1.429, p = 0.001) and AVPR2 (ω= 1.49, p = 0.001), suggesting that they could be involved in behavior and physiological changes, including those related to the domestication process. Furthermore, AVPR1a, which plays a role in social behavior, is under relaxed selective constraint in domesticated species. These results provide new insights into the nature of the domestication process and its impact on the OXT-AVP system.

FOXP in Tetrapoda: Intrinsically Disordered Regions, Short Linear Motifs and their evolutionary significance

Abstract The FOXP subfamily is probably the most extensively characterized subfamily of the forkhead superfamily, playing important roles in development and homeostasis in vertebrates. Intrinsically disorder protein regions (IDRs) are protein segments that exhibit multiple physical interactions and play critical roles in various biological processes, including regulation and signaling. IDRs in proteins may play an important role in the evolvability of genetic systems. In this study, we analyzed 77 orthologous FOXP genes/proteins from Tetrapoda, regarding protein disorder content and evolutionary rate. We also predicted the number and type of short linear motifs (SLIMs) in the IDRs. Similar levels of protein disorder (approximately 70%) were found for FOXP1, FOXP2, and FOXP4. However, for FOXP3, which is shorter in length and has a more specific function, the disordered content was lower (30%). Mammals showed higher protein disorders for FOXP1 and FOXP4 than non-mammals. Specific analyses related to linear motifs in the four genes showed also a clear differentiation between FOXPs in mammals and non-mammals. We predicted for the first time the role of IDRs and SLIMs in the FOXP gene family associated with possible adaptive novelties within Tetrapoda. For instance, we found gain and loss of important phosphorylation sites in the Homo sapiens FOXP2 IDR regions, with possible implication for the evolution of human speech.

Geografía génica de Chile: Distribución regional de los aportes genéticos americanos, europeos y africanos / Gene geography of Chile: Regional distribution of American, European and African genetic contributions

Background: The geographical distribution of genes plays a key role in genetic epidemiology. The Chilean population has three major stem groups (Native American, European and African). Aim: To estimate the regional rate of American, European and African admixture of the Chilean population. Subjects and Methods: Forty single nucleotide polymorphisms (SNP´s) which exhibit substantially different frequencies between Amerindian populations (ancestry-informative markers or AIM´s), were genotyped in a sample of 923 Chilean participants to estimate individual genetic ancestry. Results: The American, European and African individual average admixture estimates for the 15 Chilean Regions were relatively homogeneous and not statistically different. However, higher American components were found in northern and southern Chile and higher European components were found in central Chile. A negative correlation between African admixture and latitude was observed. On the average, American and European genetic contributions were similar and significantly higher than the African contribution. Weighted mean American, European and African genetic contributions of 44.34% ± 3 9%, 51.85% ± 5.44% and 3.81% ± 0.45%, were estimated. Fifty two percent of subjects harbor African genes. Individuals with Aymara and Mapuche surnames have an American admixture of 58.64% and 68.33%, respectively. Conclusions: Half of the Chilean population harbors African genes. Participants with Aymara and Mapuche surnames had a higher American genetic contribution than the general Chilean population. These results confirm the usefulness of surnames as a frst approximation to determine genetic ancestry.

No fio da navalha: raça, genética e identidades / On the razor's edge: race, genetics and identities

Em capítulos anteriores deste volume vimos que a ciência, se em certos momentos deu amplo respaldo ao conceito de raça, em outros, como no presente, oferece subsídios teóricos que o minam. Mas a trajetória de raça é sinuosa, com aproximações e distanciamentos, pactos e rupturas, que não raro se colocam de forma surpreendente. Considerando-se o atual momento teórico-metodológico da genética, neste capítulo são analisados os modos como identidades raciais podem ser, paradoxalmente, reforçadas com o uso de tecnologias genômicas conhecidas como 'marcadores informativos de ancestralidade' (MIAs). Com base na análise do sítio na Internet de uma empresa norte-americana que comercializa testes genéticos para determinação de ancestralidade, voltados para afro-americanos, procura-se aqui explorar algumas das complexas articulações entre história, ciência, genética e construção de identidades no mundo contemporâneo.

Genetic signatures of parental contribution in black and white populations in Brazil

Two hundred and three individuals classified as white were tested for 11 single nucleotide polymorphisms plus two insertion/deletions in their Y-chromosomes. A subset of these individuals (n = 172) was also screened for sequences in the first hypervariable segment of their mitochondrial DNA (mtDNA). In addition, complementary studies were done for 11 of the 13 markers indicated above in 54 of 107 black subjects previously investigated in this southern Brazilian population. The prevalence of Y-chromosome haplogroups among whites was similar to that found in the Azores (Portugal) or Spain, but not to that of other European countries. About half of the European or African mtDNA haplogroups of these individuals were related to their places of origin, but not their Amerindian counterparts. Persons classified in these two categories of skin color and related morphological traits showed distinct genomic ancestries through the country. These findings emphasize the need to consider in Brazil, despite some general trends, a notable heterogeneity in the pattern of admixture dynamics within and between populations/groups.

Mitochondrial DNA mapping of social-biological interactions in Brazilian Amazonian African-descendant populations

The formation of the Brazilian Amazonian population has historically involved three main ethnic groups, Amerindian, African and European. This has resulted in genetic investigations having been carried out using classical polymorphisms and molecular markers. To better understand the genetic variability and the micro-evolutionary processes acting in human groups in the Brazilian Amazon region we used mitochondrial DNA to investigate 159 maternally unrelated individuals from five Amazonian African-descendant communities. The mitochondrial lineage distribution indicated a contribution of 50.2 percent from Africans (L0, L1, L2, and L3), 46.6 percent from Amerindians (haplogroups A, B, C and D) and a small European contribution of 1.3 percent. These results indicated high genetic diversity in the Amerindian and African lineage groups, suggesting that the Brazilian Amazonian African-descendant populations reflect a possible population amalgamation of Amerindian women from different Amazonian indigenous tribes and African women from different geographic regions of Africa who had been brought to Brazil as slaves. The present study partially mapped the historical biological and social interactions that had occurred during the formation and expansion of Amazonian African-descendant communities.

Polymorphic variation of mononucleotide microsatellites in healthy humans and its implication for microsatellite instability screening

BACKGROUND: Colorectal cancer is the sixth most common tumor and the fifth in mortality in Brazil. Molecular markers have been associated with disease prognosis, especially in relation to therapeutic response and overall survival rates. Among these, microsatellite instability has been extensively studied. Microsatellite stability status is usually determined by comparison of normal and tumoral tissues from the same patient and instability is characterized by the difference in the PCR-amplification profile of these tissues at a given locus. Usually, a panel of five markers is used for this purpose. Two of them (BAT-25 and BAT-26) are considered monomorphic in populations of European origin. AIM: To analyse the frequency of constitutive polymorphic variation at BAT-25 and BAT-26 loci in a sample of individuals from Southern Brazil. METHODS: Two-hundred and sixteen healthy and unrelated individuals were analised to assess the frequency of allelic variation at the BAT-25 and BAT-26 loci in DNA extracted from peripheral blood. Analysis was done by polymerase chain reaction - single strand conformation polymorphism (PCR-SSCP). RESULTS: From the sample of patients studied, 7 percent and 6 percent of the patients had possible constitutive allelic variation at the BAT-25 and BAT-26 loci, respectively. CONCLUSIONS: These results indicate that significant constitutive allelic variation of these loci does occur in heterogeneous populations such as ours, and reinforce the importance of comparative studies between tumoral and corresponding normal tissue to determine microsatellite stability status and correctly identify microsatellite instability in selected populations.

RACIONAL: No Brasil, o câncer colorretal é o sexto tumor em freqüência e o quinto em mortalidade. Marcadores moleculares têm sido associados com o prognóstico da doença, especialmente em relação à resposta terapêutica e taxa de sobrevida. Dentre eles, a instabilidade de microssatélites tem sido amplamente estudada. O estado de instabilidade de microssatélites é usualmente determinado pela comparação entre tecido tumoral e tecido normal correspondente de um mesmo paciente e a instabilidade se caracteriza pela diferença no perfil do produto de amplificação por PCR destes tecidos em um determinado locus. Usualmente, é utilizado um painel de cinco marcadores para este propósito. Dois deles (BAT-25 e BAT-26) são considerados monomórficos em populações de origem européia. OBJETIVO: Analisar a freqüência de variação constitutiva nos loci BAT-25 e BAT-26 em amostra de indivíduos do sul do Brasil. MÉTODOS: Duzentos e dezesseis indivíduos saudáveis e não relacionados foram analisados para determinar a freqüência de variação alélica nestes loci. O rastreamento de variantes alélicas foi feito por "polymerase chain reaction - single strand conformation polymorphism" (PCR-SSCP). RESULTADOS: Observou-se possível variação alélica constitutiva em 7 por cento e 6 por cento dos pacientes nos loci BAT-25 e BAT-26, respectivamente. CONCLUSÃO: Estes resultados indicam que há significativa variação alélica constitucional nos loci BAT-25 e BAT-26 em grupos selecionados, como nesta amostra de indivíduos brasileiros, e reforça a importância de estudos comparativos entre tecido tumoral e o tecido normal correspondente para identificar instabilidade de microssatélites em populações determinadas.

Ribeiro's typology, genomes, and Spanish colonialism, as viewed from Gran Canaria and Colombia

Four biallelic and six multiallelic Y-chromosome polymorphisms were investigated in 59 Gran Canarian, 60 North African Berber and 46 Spanish subjects. These new data were merged with equivalent literature information to obtain the parental Y-chrosomomal contribution in Gran Canarians, Colombians, and Venezuelans. The results were then compared, for Gran Canarians and Colombians, to those derived from autosomal and mtDNA. In both groups, the Spanish Y-chromosome contribution was much more marked than that estimated using mtDNA. This analysis showed a usual trend in the Spanish Colonial history, characterized by a demographic collapse of the aboriginal population, but with considerable introgression of genes through native women. In accordance to D. Ribeiro's typology for peoples subjected to Colonialism, the Y-chromosomes of these admixed populations are classified as transplanted, their mtDNA as witness, and their autosome sets as new.

Pode a genética definir quem deve se beneficiar das cotas universitárias e demais ações afirmativas? / Can the genetics define who must benefit of university quotas and too much affirmative action?

Neste trabalho nós usamos o instrumental da genética molecular e da genética de populações para estimar quantitativamente a contribuição africana para a formação do povo brasileiro. Examinamos dois compartimentos genômicos: o DNA mitocondrial, de herança matrilínea, e o DNA nuclear, de herança bi-parental. Os estudos mitocondriais revelaram que aproximadamente 30 por cento dos brasileiros autoclassificados como brancos e 80 por cento dos negros apresentam linhagens maternas características da áfrica subsaariana. A partir destes dados, estimamos que pelo menos 89 milhões de brasileiros são afro-descendentes, um número bem superior aos 76 milhões de pessoas que se declararam negros (pretos e pardos) no censo de 2000 do IBGE. As análises de polimorfismos nucleares com marcadores "informativos de ancestralidade" mostraram resultados mais expressivos ainda. Usando estudos de brasileiros autoclassificados como brancos de várias regiões do Brasil, estimamos que aproximadamente 146 milhões de brasileiros (86 por cento da população) apresentam mais de 10 por cento de contribuição africana em seu genoma. Estes números devem ser levados em conta nas discussões sobre ações afirmativas no Brasil, mas em um sentido descritivo e não prescritivo.