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.

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.

Abstract Oxytocin receptor (OXTR) and arginine vasopressin receptors (AVPR1a, AVPR1b, and AVPR2) are paralogous genes that emerged through duplication events; along the evolutionary timeline, owing to speciation, numerous orthologues emerged as well. In order to elucidate the evolutionary forces that shaped these four genes in placental mammals and to reveal specific aspects of their protein structures, 35 species were selected. Specifically, we investigated their molecular evolutionary history and intrinsic protein disorder content, and identified the presence of short linear interaction motifs. OXTR seems to be under evolutionary constraint in placental mammals, whereas AVPR1a, AVPR1b, and AVPR2 exhibit higher evolutionary rates, suggesting that they have been under relaxed or experienced positive selection. In addition, we describe here, for the first time, that the OXTR, AVPR1a, AVPR1b, and AVPR2 mammalian orthologues preserve their disorder content, while this condition varies among the paralogues. Finally, our results reveal the presence of short linear interaction motifs, indicating possible functional adaptations related to physiological and/or behavioral taxa-specific traits.

A general introduction to the origins and history of Latin American populations is followed by a systematic review of the data from molecular autosomal assessments of the ethnic/continental (European, African, Amerindian) ancestries for 24 Latin American countries or territories. The data surveyed are of varying quality but provide a general picture of the present constitution of these populations. A brief discussion about the applications of these results (admixture mapping) is also provided. Latin American populations can be viewed as natural experiments for the investigation of unique anthropological and epidemiological issues.

A comprehensive review of uniparental systems in South Amerindians was undertaken. Variability in the Y-chromosome haplogroups were assessed in 68 populations and 1,814 individuals whereas that of Y-STR markers was assessed in 29 populations and 590 subjects. Variability in the mitochondrial DNA (mtDNA) haplogroup was examined in 108 populations and 6,697 persons, and sequencing studies used either the complete mtDNA genome or the highly variable segments 1 and 2. The diversity of the markers made it difficult to establish a general picture of Y-chromosome variability in the populations studied. However, haplogroup Q1a3a* was almost always the most prevalent whereas Q1a3* occurred equally in all regions, which suggested its prevalence among the early colonizers. The STR allele frequencies were used to derive a possible ancient Native American Q-clade chromosome haplotype and five of six STR loci showed significant geographic variation. Geographic and linguistic factors moderately influenced the mtDNA distributions (6% and 7%, respectively) and mtDNA haplogroups A and D correlated positively and negatively, respectively, with latitude. The data analyzed here provide rich material for understanding the biological history of South Amerindians and can serve as a basis for comparative studies involving other types of data, such as cultural data.

HLA-G is a non-classical HLA (Human Leukocyte Antigen) molecule characterized by limited tissue distribution under normal physiological conditions and low variability at both DNA and protein levels. Several studies suggest that HLA-G could play a role, as an immunoregulatory molecule, in situations as diverse as transplantation, cancer, viral infections and inflammatory diseases. A total of 237 individuals from 21 South American tribes speaking nine different linguistic families were studied in relation to the 14 bp insertion/deletion polymorphism at the HLA-G gene. A consistent (seven in nine) excess of heterozygosity in samples classified by language was obtained. Our data supply evidences for balancing selection acting at the HLA-G 14 bp INDEL region. Enhanced fetal survival in a pathogen-rich environment may account for these findings.

After a brief review of the most recent findings in the study of human evolution, an extensive comparison of the complete genomes of our nearest relative, the chimpanzee (Pan troglodytes), of extant Homo sapiens, archaic Homo neanderthalensis and the Denisova specimen were made. The focus was on non-synonymous mutations, which consequently had an impact on protein levels and these changes were classified according to degree of effect. A total of 10,447 non-synonymous substitutions were found in which the derived allele is fixed or nearly fixed in humans as compared to chimpanzee. Their most frequent location was on chromosome 21. Their presence was then searched in the two archaic genomes. Mutations in 381 genes would imply radical amino acid changes, with a fraction of these related to olfaction and other important physiological processes. Eight new alleles were identified in the Neanderthal and/or Denisova genetic pools. Four others, possibly affecting cognition, occured both in the sapiens and two other archaic genomes. The selective sweep that gave rise to Homo sapiens could, therefore, have initiated before the modern/archaic human divergence.

A total of 149 chickens from two different sources (one non-commercial, the other commercial) was tested for variability of the LEI0258 microsatellite. Fifty- three genotypes, explainable by 15 alleles, were found. There are clear allele and heterozygosity differences between the two samples. One of them was simultaneously studied for the MHC B-F haplotypes. Strong genetic disequilibrium was observed between the variants of the two systems, therefore providing a cheap alternative for MHC genotyping.

Folhas de 14 genótipos brasileiros de Triticum aestivum L. foram tratadas com ácido salicílico para a indução de proteínas relacionadas à patogênese (PR). Extratos inter e intracelulares foram assim obtidos e estudados através de eletroforese em gel de poliacrilamida. Sete bandas foram observadas, sendo que o material referente a duas delas (de 40 e 24 kDa) foi detectado somente nos espaços intracelulares. O DNA desses mesmos genótipos foi então amplificado através de PCR, usando iniciadores desenvolvidos a partir de três seqüências que codificam proteínas PR, e comparados com seqüências previamente descritas. Eles apresentaram homologia com os grupos PR 1, PR 3 (quitinases) e PR 5 (semelhante à taumatina), sendo que a seqüência do grupo PR 3 apresentou também um sítio característico de PRs induzidas pelo etileno e uma porção sem homologia com seqüências prévias. Não foi observada qualquer variação entre genótipos, seja nos extratos protéicos ou nas seqüências de DNA.

Leaves from 14 Brazilian genotypes of Triticum aestivum L. were treated with salicylic acid to induce pathogenesis-related (PR) proteins. Inter and intracellular extracts were then obtained and investigated through polyacrilamide gel electrophoresis. Seven bands were observed. Material related to two of them (of 40 and 24 kDa) occurred in intracellular spaces only. DNA from these same genotypes was then amplified through PCR using primers developed from three sequences encoding PR proteins, and compared with previously described sequences. The fragments presented homologies to PR groups 1, 3 (chitinases), and 5 (thaumatin-like). The PR3-like sequence also showed a site characteristic of PRs induced by ethylene and a portion without homology with previous sequences. No variation among genotypes were observed, either for protein extracts or DNA sequences.

Las migraciones desde las Islas Canarias a Venezuela han sido constantes desde la época colonial, presentando algunas regiones del país una importante influencia de ese origen. Algunos estudios han demostrado el mantenimiento de las características genéticas fundadoras en tres poblaciones semi-aisladas de la región nor-central de Venezuela. Este trabajo reporta sobre el origen del cromosoma Y en esas poblaciones, a través del análisis de cuatro marcadores bi-alélicos y tres microsatélites ubicados en su región no recombinante. Los haplogrupos Q-M3 y E-M2 , no están en esas poblaciones reflejando el origen predominantemente europeo de sus fundadores. El uso combinado de los polimorfismos bi-alélicos y los microsatélites corrobora este postulado; además, el cromosoma YAP detectado en dos de esas poblaciones está asociado con el alelo 13 del locus DYS19 el cual presenta las mas elevadas frecuencias en los Beréberes del norte de África, revelando la importancia de los hombres Beréberes en la formación de población canaria y/o la introducción de cromosomas Y Beréberes en el sur-este de España durante los siete siglos de dominación musulmana. El origen predominantemente europeo de los cromosomas Y ha sido reportado en otras áreas de América, sugiriendo que el reemplazo del cúmulo de genes aborígenes masculinos parece representar la tendencia general en el proceso de conquista y colonización del Nuevo Mundo. Tomando en consideración la clasificación propuesta por Darcy Ribeiro, nosotros proponemos la expresión genomas masculinos transplantados que refiere a la sustitución de los cromosomas Y nativos en Sur América.

Migration from the Canary Islands to Venezuela has been continuous since Colonial times, some regions of the country presenting an important Canarian influence. Earlier studies demonstrated the maintenance of the original Canarian gene pool in three north-central semi-isolated Venezuelan populations. The present study investigates the origin of the Y-chromosomes in these populations, through the analysis of four biallelic markers and three microsatellite loci located at its nonrecombining region. Haplogroups Q-M3 and E-M2 do not occur in these populations, reflecting the predominantly European origin of their male founders. The combined use of biallelic and microsatellite polymorphisms corroborated this postulation; moreover, the YAP chromosomes detected in two of these Venezuelan populations was associated with allele 13 at the DYS19 locus, which occurs with highest frequencies in Berbers from North Africa, revealing the importance of Berber males in the formation of the Canarian population and/or Berber Y-chromosome introgression during the seven centuries of the Muslim domination of Southern Spain. The predominantly European origin of the Y-chromosome had also been reported for other areas of the Americas, suggesting that the replacement of the aboriginal male background seems to represent a general trend in the process of Conquest and Colonization of the New World. Therefore, and taking into consideration the classification of the American peoples proposed by Darcy Ribeiro, we coined the expression transplanted male genome for the substitution of Native Y-chromosomes in South America

Movimentos migratórias das Ilhas Canárias para a Venezuela têm sido constantes desde os tempos coloniais, resultando que em algumas regiões deste país Sul-americano há considerável influência Canária. Anteriormente, nós conduzimos alguns estudos que demonstraram a manutenção de um pool gênico canário original em três populações Venezuelanas semi-isoladas localizadas na região centro-norte do país. Aqui, nós investigamos a origem dos cromossomos Y nestas mesmas três populações através do estudo de quatro marcadores bialélicos e três locos de microsatélites localizados na região não recombinante do cromossomo Y. Haplogrupos Q-M3 e E-M2 não foram detectados, refletindo a origem européia dos homens que fundaram estas populações. Analises combinadas utilizando os locos bialélicos juntamente com os microsatélites corroborou este achado. Cromossomos YAP detectados em duas destas populações venezuelanas mostraram estar associados com o alelo 13 do loco DYS19, sendo que esta composição apresenta suas mais altas freqüências entre os Berberes do norte da África. Este fato revela a importância dos homens Berberes na formação da população contemporânea das Ilhas Canárias e/ou a introgressão destes cromossomos no sul da Espanha durante a ocupação muçulmana da Península Ibérica. A predominância de cromossomos Y de origem européia, juntamente com a substituição do background nativo, tem também sido reportada em outras áreas do continente, sugerindo que esta é uma tendência generalizada no processo de conquista e colonização do Novo Mundo. Assim, e levando-se em consideração a classificação dos povos proposto por Darcy Ribeiro (Ribeiro, 1970), nós cunhamos a expressão "genoma masculino transplantado" para o fenômeno da substituição dos cromossomos Y nativos americanos que ocorreu na América do Sul.

O direito universal à saúde está bem estabelecido, mas entre declarações de propósitos e a realidade existem abismos difíceis de transpor. O desenvolvimento científico-tecnológico desigual tem acentuado as distâncias entre os padrões de vida, e, portanto, o estado sanitário de populações do Primeiro e Terceiro Mundos. Um dos segmentos mais importantes deste desenvolvimento científico-tecnológico é o que se relaciona à genética e à biologia molecular. Os avanços espetaculares nesta área fazem com que nossas vidas sejam cada vez mais "genetizadas". Procurou-se abordar, aqui, as relações entre essas áreas e a da saúde pública no que se refere a (a) doenças infecciosas; (b) enfermidades mendelianas; (c) aberrações cromossômicas; (d) condições multifatoriais; (e) mutagênese, teratogênese, carcinogênese; e (f) hemoglobinopatias e talassemias. O futuro da saúde pública no país está longe de ser promissor, mas deve-se fazer um esforço para a montagem de programas apropriados neste setor que envolvam inversões apropriadas, tanto na infra-estrutura como na formação de recursos humanos; e tais programas não podem se dar ao luxo de ignorar a genética e a biologia molecular.

The universal right to health is well established, but between declarations of principles and reality there are gaps difficult to transpose. Unequal scientific-technological developments have enlarged the distances between standards of living, and therefore of the health conditions, of 1st and 3rd World populations. One of the most important areas of this scientific-technological development is that related to genetics and molecular biology. The spectacular advances in this area are conditioning that human life is becoming more and more "geneticized". The present review considered the relations between these areas and that of public health with reference to (a) infectious diseases; (b) mendelian illnesses; (c) chromosome aberrations; (d) multifactorial conditions; (e) mutagenesis, teratogenesis, carcinogenesis; (f) hemoglobinopathies and thalassemias. The future of Brazil's public health is far from promising, but an effort should be made for the establishment of programs in this sector that would involve appropriate inversions both in infrastructure and the formation of human resources; and such programs cannot afford the luxury of ignoring genetics and molecular biology.

O direito universal à saúde está bem estabelecido, mas entre declarações de propósitos e a realidade existem abismos difíceis de transpor. O desenvolvimento científico-tecnológico desigual tem acentuado as distâncias entre os padrões de vida, e, portanto, o estado sanitário de populações do Primeiro e Terceiro Mundos. Um dos segmentos mais importantes deste desenvolvimento científico-tecnológico é o que se relaciona à genética e à biologia molecular. Os avanços espetaculares nesta área fazem com que nossas vidas sejam cada vez mais "genetizadas". Procurou-se abordar, aqui, as relações entre essas áreas e a da saúde pública no que se refere a (a) doenças infecciosas; (b) enfermidades mendelianas; (c) aberrações cromossômicas; (d) condições multifatoriais; (e) mutagênese, teratogênese, carcinogênese; e (f) hemoglobinopatias e talassemias. O futuro da saúde pública no país está longe de ser promissor, mas deve-se fazer um esforço para a montagem de programas apropriados neste setor que envolvam inversões apropriadas, tanto na infra-estrutura como na formação de recursos humanos; e tais programas não podem se dar ao luxo de ignorar a genética e a biologia molecular.

The universal right to health is well established, but between declarations of principles and reality there are gaps difficult to transpose. Unequal scientific-technological developments have enlarged the distances between standards of living, and therefore of the health conditions, of 1st and 3rd World populations. One of the most important areas of this scientific-technological development is that related to genetics and molecular biology. The spectacular advances in this area are conditioning that human life is becoming more and more "geneticized". The present review considered the relations between these areas and that of public health with reference to (a) infectious diseases; (b) mendelian illnesses; (c) chromosome aberrations; (d) multifactorial conditions; (e) mutagenesis, teratogenesis, carcinogenesis; (f) hemoglobinopathies and thalassemias. The future of Brazil's public health is far from promising, but an effort should be made for the establishment of programs in this sector that would involve appropriate inversions both in infrastructure and the formation of human resources; and such programs cannot afford the luxury of ignoring genetics and molecular biology.