Resumo em Inglês:

The questions of the title have been considered in several ways. First, indications of the traits which make us humans were considered. Then the behavior and culture concepts were examined, and the biology and culture interactions discussed, with an emphasis on the similarities and differences between the genetic and cultural transmissions. Next diverse types of selective pressures were reviewed, and finally pessimistic and optimistic views of our future contrasted. Vigorous action against acts which lead to exclusion and discriminatory policies against human subjects is needed.

Resumo em Inglês:

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.

Resumo em Inglês:

Genetic studies have long suggested the important role of the DRD2 gene in psychiatric disorders and behavior. Further research has shown a conjoined effect of genes in the Chr11q22-23 region, which includes the NCAM1, TTC12, ANKK1 and DRD2 genes, or NTAD cluster. Despite a growing need to unravel the role of this cluster, few studies have taken into account interspecies and evolutionary approaches. This study shows that behaviorally relevant SNPs from the NTAD cluster, such as rs1800497 (Taq1A) and rs6277, are ancient polymorphisms that date back to the common ancestor between modern humans and Neanderthals/Denisovans. Conserved synteny and neighborhood indicate the NTAD cluster seems to have been established at least 400 million years ago, when the first Sarcopterygians emerged. The NTAD genes are apparently co-regulated and this could be attributed to adaptive functional properties, including those that emerged when the central nervous system became more complex. Finally, our findings indicate that NTAD genes, which are related to neurogenesis and dopaminergic neurotransmission, should be approached as a unit in behavioral and psychiatric genetic studies.

Resumo em Inglês:

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.

Resumo em Inglês:

After the first description of a patient recognized as a MPS case was made in 1917, several similar cases were described and identified. Observations reported in the middle of the twentieth century concerning the presence of acid mucopolysaccharides (later called glycosaminoglycans, or GAGs) in tissues and especially in urine of patients were instrumental in providing an identity for these diseases, which became referred as "mucopolysaccharidoses" (MPS). In the late 1960's it was demonstrated that MPS were caused by defects in the breakdown of GAGs, and the specific enzyme deficiencies for the 11 types and subtypes of MPS were identified thereafter. Genes involved in the MPS were subsequently identified, and a large number of disease-causing mutations were identified in each one. Although individually rare, MPS are relatively frequent as a group, with an overall incidence estimated as 1:22,000. The increased excretion of urinary GAGs observed in the vast majority of MPS patients provides a simple screening method, the diagnosis usually being confirmed by the identification of the specific enzyme deficiency. Molecular analysis also plays a role, being helpful for phenotype prediction, prenatal diagnosis and especially for the identification of carriers. As the diseases are rare and diagnosis requires sophisticated methods, the establishment of reference laboratories for MPS identification is recommended. The successful experience of the MPS Brazil Network in providing access to information and diagnosis may be considered as an option for developing countries. The development of therapeutic strategies for MPS, including bone marrow/hematopoietic stem cell transplantation (BMT/HSCT) and enzyme replacement therapy (ERT), changed the natural history of many MPS types. However, some challenges still remain, including the prevention of cognitive decline which occurs in some MPS. Newer approaches, such as intratechal ERT, substrate reduction therapy, read-through, gene therapy and encapsulated modified cells may provide a better outcome for these diseases in the near future. As early diagnosis and early treatment seems to improve treatment outcomes, and as newborn screening is now technically feasible, pilot programs (including one in progress in an area with high-incidence of MPS VI in northeastern Brazil) should provide information about its potential impact in reducing the morbidity associated with MPS diseases.

Resumo em Inglês:

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric condition of children worldwide. This disorder is defined by a combination of symptoms of inattention and hyperactivity/impulsivity. Diagnosis is based on a sufficient number of symptoms causing impairment in these two domains determining several problems in personal and academic life. Although genetic and environmental factors are important in ADHD etiology, how these factors influence the brain and consequently behavior is still under debate. It seems to be consensus that a fronto-subcortical dysfunction is responsible, at least in part, for the ADHD phenotype spectrum. The main results from association and pharmacogenetic studies performed in Brazil are discussed. The investigations performed so far on ADHD genetics in Brazil and elsewhere are far from conclusive. New plausible biological hypotheses linked to neurotransmission and neurodevelopment, as well as new analytic approaches are needed to fully disclose the genetic component of the disorder.

Resumo em Inglês:

The TP53 gene, first described in 1979, was identified as a tumor suppressor gene in 1989, when it became clear that its product, the p53 nuclear phosphoprotein, was frequently inactivated in many different forms of cancers. Nicknamed "guardian of the genome", TP53 occupies a central node in stress response networks. The p53 protein has a key role as transcription factor in limiting oncogenesis through several growth suppressive functions, such as initiating apoptosis, senescence, or cell cycle arrest. The p53 protein is directly inactivated in about 50% of all tumors as a result of somatic gene mutations or deletions, and over 80% of tumors demonstrate dysfunctional p53 signaling. Beyond the undeniable importance of p53 as a tumor suppressor, an increasing number of new functions for p53 have been reported, including its ability to regulate energy metabolism, to control autophagy, and to participate in various aspects of differentiation and development. Recently, studies on genetic variations in TP53 among different populations have led to the notion that the p53 protein might play an important role in regulating fertility. This review summarizes current knowledge on the basic functions of different genes of the TP53 family and TP53 pathway with respect to fertility. We also provide original analyses based on genomic and genotype databases, providing further insights into the possible roles of the TP53 pathway in human reproduction.

Resumo em Inglês:

The specific treatment available for Fabry disease (FD) is enzyme replacement therapy (ERT) with agalsidase alfa or beta. A systematic review and meta-analysis was conducted to assess the efficacy and safety of ERT for FD. Only double-blind, randomized clinical trials (RCTs) comparing agalsidase alfa or beta and placebo were included. ERT with either agalsidase alfa or beta was considered similar for the purposes of analysis. Ten RCTs were identified, which showed improvements in neuropathic pain, in heart abnormalities and in globotriaosylceramide (GL-3) levels. A meta-analysis showed increased odds for fever, rigors, development of IgG antibodies to agalsidase, and no significant association with development of hypertension or reduction in the QRS complex duration on electrocardiogram. The RCTs included in this comparison enrolled few patients, were highly heterogeneous, and were focused mainly on surrogate endpoints, limiting any conclusions as to the real effect of ERT for FD. The available evidence suggests that response to ERT is variable across patient subgroups and that agalsidase may slow progression of FD, with slight improvement of existing changes. Nevertheless, many uncertainties remain, and further studies are necessary.

Resumo em Inglês:

Spinal muscular atrophy (SMA) is an autosomal recessive inherited disorder caused by alterations in the survival motor neuron I (SMN1) gene. SMA patients are classified as type I-IV based on severity of symptoms and age of onset. About 95% of SMA cases are caused by the homozygous absence of SMN1 due to gene deletion or conversion into SMN2. PCR-based methods have been widely used in genetic testing for SMA. In this work, we introduce a new approach based on TaqMan® real-time PCR for research and diagnostic settings. DNA samples from 100 individuals with clinical signs and symptoms suggestive of SMA were analyzed. Mutant DNA samples as well as controls were confirmed by DNA sequencing. We detected 58 SMA cases (58.0%) by showing deletion of SMN1 exon 7. Considering clinical information available from 56 of them, the patient distribution was 26 (46.4%) SMA type I, 16 (28.6%) SMA type II and 14 (25.0%) SMA type III. Results generated by the new method was confirmed by PCR-RFLP and by DNA sequencing when required. In conclusion, a protocol based on real-time PCR was shown to be effective and specific for molecular analysis of SMA patients.

Resumo em Inglês:

Prenatal alcohol exposure can have serious and permanent adverse effects. The developing brain is the most vulnerable organ to the insults of prenatal alcohol exposure. A behavioral phenotype of prenatal alcohol exposure including conduct disorders is also described. This study on a sample of Brazilian adolescents convicted for criminal behavior aimed to evaluate possible clinical features of Fetal Alcohol Syndrome (FAS). These were compared to a control group of school adolescents, as well as tested for other environmental risk factors for antisocial behavior. A sample of 262 institutionalized male adolescents due to criminal behavior and 154 male students aged between 13 and 21 years comprised the study population. Maternal use of alcohol was admitted by 48.8% of the mothers of institutionalized adolescents and by 39.9% of the school students. In this sample of adolescents we could not identify -individual cases with a clear diagnosis of FAS, but signs suggestive of FASD were more common in the institutionalized adolescents. Social factors like domestic and family violence were frequent in the risk group, this also being associated to maternal drinking during pregnancy. The inference is that in our sample, criminal behavior is more related to complex interactions between environmental and social issues including prenatal alcohol exposure.

Resumo em Inglês:

Drosophila willistoni (Insecta, Diptera) is considered a paradigm for evolutionary studies. Their chromosomes are characterized by multiple paracentric inversions that make it hard to identify and describe chromosomal poly-morphisms. In the present report we attempted to systematize the description of all the 50 inversions found in the last three decades, since we have been studying the chromosomes of several individuals of 30 different populations, including the one used in the genome sequencing project (Gd-H4-1). We present the photographic register of 11 arrangements in the left arm of the X chromosome (XL), eight in the right arm (XR), 10 in the left arm of chromosome II (IIL), eight in its right arm (IIR) and 13 in chromosome III. This information also includes their breakpoints on the reference photomap. A clear geographic difference was detected in XL and XR, with different fixed arrangements depending on the origin of the population studied. Through the comparison of all X arrangements it was possible to infer the putative ancestral arrangements, i.e., those related to all the remaining arrangements through the small number of inversions that occurred in the past, which we will call XL-A and XR-A. In the autosomes (IIL/IIR and III), fixed inversions were detected, but most are segregating in different frequencies along the geographical distribution of the D. willistoni populations.

Resumo em Inglês:

Wolbachia are endosymbiotic bacteria that commonly infect arthropods, inducing certain phenotypes in their hosts. So far, no endemic South American species of terrestrial isopods have been investigated for Wolbachia infection. In this work, populations from two species of Balloniscus (B. sellowii and B. glaber) were studied through a diagnostic PCR assay. Fifteen new Wolbachia 16S rDNA sequences were detected. Wolbachia found in both species were generally specific to one population, and five populations hosted two different Wolbachia 16S rDNA sequences. Prevalence was higher in B. glaber than in B. sellowii, but uninfected populations could be found in both species. Wolbachia strains from B. sellowii had a higher genetic variation than those isolated from B. glaber. AMOVA analyses showed that most of the genetic variance was distributed among populations of each species rather than between species, and the phylogenetic analysis suggested that Wolbachia strains from Balloniscus cluster within Supergroup B, but do not form a single monophyletic clade, suggesting multiple infections for this group. Our results highlight the importance of studying Wolbachia prevalence and genetic diversity in Neotropical species and suggest that South American arthropods may harbor a great number of diverse strains, providing an interesting model to investigate the evolution of Wolbachia and its hosts.

Resumo em Inglês:

We describe variation at microsatellite loci and the chromosomal polymorphisms of a hybrid population, and hybridizing populations of Ctenomys minutus (the minor tuco-tuco) from the coastal plain of Rio Grande do Sul, southern Brazil. Cytogenetic analysis and a survey of six microsatellite loci included 101 specimens of C. minutus from the parental populations (2n/AN = 42/74 and 48a/76) and their contact zone. Cytogenetic analysis recorded 26 different karyotypes exhibited by 50 individuals from the hybrid population. Of the 26 karyotypes, only 14% presented a parental-like configuration, and none had the combinations of 2n and AN expected for an F1 hybrid. The remaining karyotypes were alternative hybrid forms, with 2n varying from 42 to 46 and AN from 68 to 80. These results suggest chromosomal rearrangements are only of minor significance in the establishment of reproductive barriers for this species.

Resumo em Inglês:

Transgenic plants represent an invaluable tool for molecular, genetic, biochemical and physiological studies by gene overexpression or silencing, transposon-based mutagenesis, protein sub-cellular localization and/or promoter characterization as well as a breakthrough for breeding programs, allowing the production of novel and genetically diverse genotypes. However, the stable transformation of soybean cannot yet be considered to be routine because it depends on the ability to combine efficient transformation and regeneration techniques. Two methods have been used with relative success to produce completely and stably transformed plants: particle bombardment and the Agrobacterium tumefaciens system. In addition, transformation by Agrobacterium rhizogenes has been used as a powerful tool for functional studies. Most available information on gene function is based on heterologous expression systems. However, as the activity of many promoters or proteins frequently depends on specific interactions that only occur in homologous backgrounds, a final confirmation based on a homologous expression system is desirable. With respect to soybean biotech improvement, transgenic lines with agronomical, nutritional and pharmaceutical traits have been obtained, including herbicide-tolerant soybeans, which represented the principal biotech crop in 2011, occupying 47% of the global biotech area.

Resumo em Inglês:

When plants are exposed to stressful environmental conditions, the production of Reactive Oxygen Species (ROS) increases and can cause significant damage to the cells. Antioxidant defenses, which can detoxify ROS, are present in plants. A major hydrogen peroxide detoxifying system in plant cells is the ascorbate-glutathione cycle, in which, ascorbate peroxidase (APX) enzymes play a key role catalyzing the conversion of H2O2 into H2O, using ascorbate as a specific electron donor. Different APX isoforms are present in distinct subcellular compartments, such as chloroplasts, mitochondria, peroxisome, and cytosol. The expression of APX genes is regulated in response to biotic and abiotic stresses as well as during plant development. The APX responses are directly involved in the protection of plant cells against adverse environmental conditions. Furthermore, mutant plants APX genes showed alterations in growth, physiology and antioxidant metabolism revealing those enzymes involvement in the normal plant development.

Resumo em Inglês:

Bromeliaceae is a morphologically distinctive and ecologically diverse family originating in the New World. Three centers of diversity, 58 genera, and about 3,140 bromeliad species are currently recognized. We compiled all of the studies related to the reproductive biology, genetic diversity, and population structure of the Bromeliaceae, and discuss the evolution and conservation of this family. Bromeliads are preferentially pollinated by vertebrates and show marked variation in breeding systems, from predominant inbreeding to predominant outcrossing, as well as constancy in chromosome number (2n = 2x = 50). Autogamous or mixed mating system bromeliads have a high inbreeding coefficient (F IS), while outcrossing species show low F IS. The degree of differentiation among populations (F ST) of species ranges from 0.043 to 0.961, which can be influenced by pollen and seed dispersal effects, clonal growth, gene flow rates, and connectivity among populations. The evolutionary history of the Bromeliaceae is poorly known, although some studies have indicated that the family arose in the Guayana Shield roughly 100 Mya. We believe that genetic, cytogenetic, and reproductive data will be essential for diagnosing species status and for assisting conservation programs.

Resumo em Inglês:

Plants of the family Iridaceae are well represented in the grassland vegetation of southern Brazil, occurring in the Pampa and Atlantic Forest biomes. Nevertheless, little is known about the taxonomy and evolution of Iridaceae species in southern Brazil. The main goal of this review is to compile published information about South American Iridaceae, and to discuss the evolution and genetic diversity of the family presenting our own research data in the light of the published literature. The main focus is on the genera Calydorea, Cypella, Herbertia, and Sisyrinchium. Aspects of reproductive system and of pollinator attraction are also discussed.

Resumo em Inglês:

As part of a long-term investigation on the evolution of Passiflora L., we investigated the divergence ages of the genus and diversification of its subgenera, relating them with biogeographical and/or historical events, and other characteristics of this taxon. The main aim of the present work was to evaluate the biogeographic distribution of this genus to better understand its evolutionary history. This is the first time that representatives from South American and Old World Passifloraceae genera have been studied as a group comprising a total of 106 widely distributed species, with representative samples of the four suggested subgenera. Seven DNA regions were studied, comprising 7,431 nucleotides from plastidial, mitochondrial and nuclear genomes. Divergence time estimates were obtained by using a Bayesian Markov Chain Monte Carlo method and a random local clock model for each partition. Three major subgenera have been shown to be monophyletic and here we are proposing to include another subgenus in the Passiflora infrageneric classification. In general, divergence among the four subgenera in Passiflora is very ancient, ranging from ~32 to ~38 Mya, and Passifloraceae seems to follow a biogeographic scenario proposed for several plant groups, originating in Africa, crossing to Europe/Asia and arriving in the New World by way of land bridges. Our results indicated that Passiflora ancestors arrived in Central America and diversified quickly from there, with many long distance dispersion events.

Resumo em Inglês:

Bacteria that colonize plant roots and promote plant growth are referred to as plant growth-promoting rhizobacteria (PGPR). PGPR are highly diverse and in this review we focus on rhizobacteria as biocontrol agents. Their effects can occur via local antagonism to soil-borne pathogens or by induction of systemic resistance against pathogens throughout the entire plant. Several substances produced by antagonistic rhizobacteria have been related to pathogen control and indirect promotion of growth in many plants, such as siderophores and antibiotics. Induced systemic resistance (ISR) in plants resembles pathogen-induced systemic acquired resistance (SAR) under conditions where the inducing bacteria and the challenging pathogen remain spatially separated. Both types of induced resistance render uninfected plant parts more resistant to pathogens in several plant species. Rhizobacteria induce resistance through the salicylic acid-dependent SAR pathway, or require jasmonic acid and ethylene perception from the plant for ISR. Rhizobacteria belonging to the genera Pseudomonas and Bacillus are well known for their antagonistic effects and their ability to trigger ISR. Resistance-inducing and antagonistic rhizobacteria might be useful in formulating new inoculants with combinations of different mechanisms of action, leading to a more efficient use for biocontrol strategies to improve cropping systems.

Resumo em Inglês:

Eukaryotic cells have developed mechanisms to prevent genomic instability, such as DNA damage detection and repair, control of cell cycle progression and cell death induction. The bifunctional compound furocumarin 8-methoxy-psoralen (8-MOP) is widely used in the treatment of various inflammatory skin diseases. In this review, we summarize recent data about the role of chromatin remodeling in the repair of DNA damage induced by treatment with 8-methoxypsoralen plus UVA (8-MOP+UVA), focusing on repair proteins in budding yeast Saccharomyces cerevisiae, an established model system for studying DNA repair pathways. The interstrand crosslinks (ICL) formed by the 8-MOP+UVA treatment are detrimental lesions that can block transcription and replication, leading to cell death if not repaired. Current data show the involvement of different pathways in ICL processing, such as nucleotide excision repair (NER), base excision repair (BER), translesion repair (TLS) and double-strand break repair. 8-MOP+UVA treatment in yeast enhances the expression of genes involved in the DNA damage response, double strand break repair by homologous replication, as well as genes related to cell cycle regulation. Moreover, alterations in the expression of subtelomeric genes and genes related to chromatin remodeling are consistent with structural modifications of chromatin relevant to DNA repair. Taken together, these findings indicate a specific profile in 8-MOP+UVA responses related to chromatin remodeling and DNA repair.

Resumo em Inglês:

Our mutagenesis group has been studying with important economic drivers of our state, such as agriculture, the footwear and leather industry and open-cast coal mining. Working conditions in these sectors have potentially harmful to humans. The aim of these studies is to determine the health risk of workers by biomonitoring subjects exposed to genotoxic agents. The main results of our studies with vineyard farmers we observed a high rate of MN and DNA damage in individuals exposed to pesticides (p < 0.001). In addition, some effects of genetic polymorphisms in the modulation of MN results were observed in this group. Tobacco farmers were also evaluated at different crop times. The results showed a significant increase in the Damage index and frequency in tobacco farmers compared to the non-exposed group, for all crop times. The results for footwear and tannery workers showed a significant increase in the mean ID for the solvent-based adhesive (p < 0.001) group in comparison to the water-based adhesive group and control (p < 0.05). For open-cast coal mine workers, the EBCyt indicated a significant increase in nuclear bud frequency and cytokinetic defects in the exposed group compared to the non-exposed group (p < 0.0001). We were able to associate specific genetic susceptibility with each type of exposure and with the non-use or improper use of personal protection equipment and diet adequacy. These results show how important the continuous education of exposed workers is to minimizing the effect of the occupational exposure and the risk of disease associated with the work.

Resumo em Inglês:

MicroRNAs (miRNAs) have been identified as key molecules in regulatory networks. The fine-tuning role of miRNAs in addition to the regulatory role of transcription factors has shown that molecular events during development are tightly regulated. In addition, several miRNAs play crucial roles in the response to abiotic stress induced by drought, salinity, low temperatures, and metals such as aluminium. Interestingly, several miRNAs have overlapping roles with regard to development, stress responses, and nutrient homeostasis. Moreover, in response to the same abiotic stresses, different expression patterns for some conserved miRNA families among different plant species revealed different metabolic adjustments. The use of deep sequencing technologies for the characterisation of miRNA frequency and the identification of new miRNAs adds complexity to regulatory networks in plants. In this review, we consider the regulatory role of miRNAs in plant development and abiotic stresses, as well as the impact of deep sequencing technologies on the generation of miRNA data.

Resumo em Inglês:

Recent advances in nucleic acid sequencing technology are creating a diverse landscape for the analysis of horizontal transfer in complete genomes. Previously limited to prokaryotes, the availability of complete genomes from close eukaryotic species presents an opportunity to validate hypotheses about the patterns of evolution and mechanisms that drive horizontal transfer. Many of those methods can be transported from methods previously used in prokaryotic genomes, as the assumptions for horizontal transfer can be interpreted as the same. Some methods, however, require a complete adaptation, while others need refinements in sensitivity and specificity to deal with the huge datasets generated from next-generation sequencing technologies. Here we list the types of methods used for horizontal transfer detection, as well as theirs strengths and weakness.