RESUMEN
The major histocompatibility complex (MHC) enables vertebrates to cope with pathogens and maintain healthy populations, thus making it a unique set of loci for addressing ecology and evolutionary biology questions. The aim of our study was to examine the variability of Heermann's Gull MHC class II (MHCIIB) and compare these loci with other Charadriiformes. Fifty-nine MHCIIB haplotypes were recovered from sixty-eight Heermann's Gulls by cloning, of them, twelve were identified as putative true alleles, forty-five as unique alleles, and two as pseudogenes. Intra and interspecific relationships indicated at least two loci in Heermann's Gull MHCIIB and trans-species polymorphism among Charadriiformes (coinciding with the documented evidence of two ancient avian MHCIIB lineages, except in the Charadriidae family). Additionally, sites under diversifying selection revealed a better match with peptide-binding sites inferred in birds than those described in humans. Despite the negative anthropogenic activity reported on Isla Rasa, Heermann's Gull showed MHCIIB variability consistent with population expansion, possibly due to a sudden growth following conservation efforts. Duplication must play an essential role in shaping Charadriiformes MHCIIB variability, buffering selective pressures through balancing selection. These findings suggest that MHC copy number and protected islands can contribute to seabird conservation.
Asunto(s)
Charadriiformes , Animales , Aves/genética , Charadriiformes/genética , Genes MHC Clase II/genética , Antígenos de Histocompatibilidad Clase II/genética , Humanos , Filogenia , Selección GenéticaRESUMEN
The major histocompatibility complex (MHC) is an important gene complex contributing to adaptive immunity. Studies of platyrrhine MHC have focused on identifying experimental models of immune system function in the equivalent Human Leukocyte Antigen (HLA). These genes have thus been explored primarily in captive platyrrhine individuals from research colonies. However, investigations of standing MHC variation and evolution in wild populations are essential to understanding its role in immunity, sociality and ecology. Capuchins are a promising model group exhibiting the greatest habitat diversity, widest diet breadth and arguably the most social complexity among platyrrhines, together likely resulting in varied immunological challenges. We use high-throughput sequencing to characterize polymorphism in four Class II DR and DQ exons for the first time in seven capuchin species. We find evidence for at least three copies for DQ genes and at least five for DRB, with possible additional unrecovered diversity. Our data also reveal common genotypes that are inherited across our most widely sampled population, Cebus imitator in Sector Santa Rosa, Costa Rica. Notably, phylogenetic analyses reveal that platyrrhine DQA sequences form a monophyletic group to the exclusion of all Catarrhini sequences examined. This result is inconsistent with the trans-species hypothesis for MHC evolution across infraorders in Primates and provides further evidence for the independent origin of current MHC genetic diversity in Platyrrhini. Identical allele sharing across cebid species, and more rarely genera, however, does underscore the complexity of MHC gene evolution and the need for more comprehensive assessments of allelic diversity and genome structure.
Asunto(s)
Cebus/inmunología , Evolución Molecular , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Alelos , Secuencia de Aminoácidos/genética , Animales , Cebus/genética , Costa Rica , Genes MHC Clase II/genética , Genes MHC Clase II/inmunología , Antígenos HLA-DQ/inmunología , Antígenos HLA-DR/inmunología , Humanos , Filogenia , Polimorfismo Genético/inmunologíaRESUMEN
Peptide research has increased during the last years due to their applications as biomarkers, therapeutic alternatives or as antigenic sub-units in vaccines. The implementation of computational resources have facilitated the identification of novel sequences, the prediction of properties, and the modelling of structures. However, there is still a lack of open source protocols that enable their straightforward analysis. Here, we present PepFun, a compilation of bioinformatics and cheminformatics functionalities that are easy to implement and customize for studying peptides at different levels: sequence, structure and their interactions with proteins. PepFun enables calculating multiple characteristics for massive sets of peptide sequences, and obtaining different structural observables derived from protein-peptide complexes. In addition, random or guided library design of peptide sequences can be customized for screening campaigns. The package has been created under the python language based on built-in functions and methods available in the open source projects BioPython and RDKit. We present two tutorials where we tested peptide binders of the MHC class II and the Granzyme B protease.
Asunto(s)
Quimioinformática/métodos , Biología Computacional/métodos , Péptidos/metabolismo , Genes MHC Clase II/genética , Granzimas/metabolismo , Proteínas/metabolismoRESUMEN
Pathogen diversity is a key source of selective pressure on immune system genes, shaping molecular evolution mainly on widely distributed or migratory organisms such as cetaceans. Here, we investigated the effects of latitudinal span migration, different biomes occupation, and pathogen-mediated selection on MHC DQB locus divergence on cetaceans. We applied some evolutionary genetics methods using a dataset of 15 species and 121 sequences, and we found a trend on greater MHC divergence on tropical species when compared with either temperate or migratory species. In addition, oceanic cetaceans exhibit greater MHC divergence. Here, we show that, despite there was a correlation between the diversity of MHC DQB alleles with the distribution of organisms, the pattern of diversity found is not completely explained by pathogenic pressure, suggesting that other factors must be investigated for a better understanding of the processes related to the diversity of MHC in cetaceans.
Asunto(s)
Cetáceos/genética , Cetáceos/inmunología , Evolución Molecular , Genes MHC Clase II/genética , Variación Genética , Selección Genética , Animales , Ecosistema , Genes MHC Clase II/inmunología , FilogeniaRESUMEN
Melkersson-Rosenthal syndrome (MRS) is a neuromucocutaneous disease that manifests by the triad of recurrent orofacial edema (frequently as cheilitis granulomatosa), relapsing facial paralysis and plicated tongue. The cause of MRS remains unknown, but genetic predisposal and a relationship with inflammatory bowel disease are suspected. The objective of this research was to compare the frequency of class I and II HLA alleles in patients with a confirmed diagnosis of MRS with those of a healthy control group. We conduct a case-control study and typed of HLA A, B, C, DR, and DQ using molecular techniques. The study included 36 patients with MRS and 297 patients in the control group. There was an increase in the expression of HLA A*02 (p = 0.0269; OR: 1,79 [1,045-2,973]), HLA DRB1*11 (p < 0,0001; OR: 4,009 [2,214-7,277]), HLA DRB1*13 (not statistically significant) and HLA DQB1*03 (p = 0,0177; OR: 1,829 [1,122-2,978]) and low levels of HLA A*01 (p = 0.0046; OR: 0,097 [0,009-0,538]), HLA DRB1*04 (p = 0.0274; OR: 0,228 [0,053-0,844]), HLA DRB1*07 (p = 0,0091; OR: 0,183 [0,043-0,670]) and HLA DQB1*02 (p = 0.0051; OR: 0,312 [0,143-0,721]) in MRS patients compared with the control group. Crohn disease (CD) patients had disparate genetic profiles versus those with MRS. This single-institution study had a small cohort, because this disease is rare. Conclusions: There is a genetic predisposition toward MRS, involving associated and protective genes.
Asunto(s)
Alelos , Cadenas HLA-DRB1/genética , Complejo Mayor de Histocompatibilidad/genética , Síndrome de Melkersson-Rosenthal/genética , Adolescente , Adulto , Anciano , Brasil , Estudios de Casos y Controles , Niño , Preescolar , Enfermedad de Crohn/genética , Femenino , Genes MHC Clase I/genética , Genes MHC Clase II/genética , Predisposición Genética a la Enfermedad , Granulomatosis Orofacial/genética , Cadenas beta de HLA-DQ , Humanos , Lactante , Enfermedades Inflamatorias del Intestino , Masculino , Persona de Mediana Edad , Pacientes , Adulto JovenRESUMEN
OBJECTIVE: The MHC region harbors the strongest loci for latent autoimmune diabetes in adults (LADA); however, the strength of association is likely attenuated compared with that for childhood-onset type 1 diabetes. In this study, we recapitulate independent effects in the MHC class I region in a population with type 1 diabetes and then determine whether such conditioning in LADA yields potential genetic discriminators between the two subtypes within this region. RESEARCH DESIGN AND METHODS: Chromosome 6 was imputed using SNP2HLA, with conditional analysis performed in type 1 diabetes case subjects (n = 1,985) and control subjects (n = 2,219). The same approach was applied to a LADA cohort (n = 1,428) using population-based control subjects (n = 2,850) and in a separate replication cohort (656 type 1 diabetes case, 823 LADA case, and 3,218 control subjects). RESULTS: The strongest associations in the MHC class II region (rs3957146, ß [SE] = 1.44 [0.05]), as well as the independent effect of MHC class I genes, on type 1 diabetes risk, particularly HLA-B*39 (ß [SE] = 1.36 [0.17]), were confirmed. The conditional analysis in LADA versus control subjects showed significant association in the MHC class II region (rs3957146, ß [SE] = 1.14 [0.06]); however, we did not observe significant independent effects of MHC class I alleles in LADA. CONCLUSIONS: In LADA, the independent effects of MHC class I observed in type 1 diabetes were not observed after conditioning on the leading MHC class II associations, suggesting that the MHC class I association may be a genetic discriminator between LADA and childhood-onset type 1 diabetes.
Asunto(s)
Diabetes Mellitus Tipo 1/genética , Genes MHC Clase II/genética , Genes MHC Clase I/genética , Pruebas Genéticas , Diabetes Autoinmune Latente del Adulto/genética , Adolescente , Adulto , Edad de Inicio , Alelos , Estudios de Casos y Controles , Niño , Preescolar , Cromosomas Humanos Par 6/genética , Estudios de Cohortes , Diabetes Mellitus Tipo 1/clasificación , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Diagnóstico Diferencial , Femenino , Estudios de Asociación Genética , Pruebas Genéticas/métodos , Humanos , Diabetes Autoinmune Latente del Adulto/clasificación , Diabetes Autoinmune Latente del Adulto/diagnóstico , Masculino , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
OBJECTIVE: To study the genetic susceptibility to neuromyelitis optica (NMO) as well as the relationship between HLA genotypes and susceptibility to the disease in the southern Brazilian population. METHODS: We analyzed patients with NMO, who met criteria for Wingerchuk's diagnosis of NMO, with detected serum anti-AQP4-IgG antibody. The HLA genotyping was performed by high-resolution techniques (Sanger sequencing) in patients and controls. The HLA genotypes were statistically compared with a paired control population. RESULTS: The HLA genotyping revealed the diversity of the southern Brazilian population whose HLA profile resembled European and Asian populations. Some alleles had statistical correlations with a positive association (increased susceptibility) with NMO, particularly the HLA-DRB1*04:05 and *16:02. CONCLUSIONS: In our study, the HLA genotype was different to that previously reported for other Brazilian populations. Although our study had a small cohort, HLA genotypes were associated with increased susceptibility to NMO for HLA-DRB1*04:05 and *16:02. The alleles of HLA class I HLA-A*02:08 and *30:09, HLA-B*08:04 and *35:04 showed an association before the Bonferroni correction.
Asunto(s)
Alelos , Genes MHC Clase II/genética , Genes MHC Clase I/genética , Predisposición Genética a la Enfermedad/genética , Antígenos HLA/genética , Neuromielitis Óptica/genética , Adulto , Brasil , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Valores de Referencia , Adulto JovenRESUMEN
ABSTRACT Objective: To study the genetic susceptibility to neuromyelitis optica (NMO) as well as the relationship between HLA genotypes and susceptibility to the disease in the southern Brazilian population. Methods: We analyzed patients with NMO, who met criteria for Wingerchuk's diagnosis of NMO, with detected serum anti-AQP4-IgG antibody. The HLA genotyping was performed by high-resolution techniques (Sanger sequencing) in patients and controls. The HLA genotypes were statistically compared with a paired control population. Results: The HLA genotyping revealed the diversity of the southern Brazilian population whose HLA profile resembled European and Asian populations. Some alleles had statistical correlations with a positive association (increased susceptibility) with NMO, particularly the HLA-DRB1*04:05 and *16:02. Conclusions: In our study, the HLA genotype was different to that previously reported for other Brazilian populations. Although our study had a small cohort, HLA genotypes were associated with increased susceptibility to NMO for HLA-DRB1*04:05 and *16:02. The alleles of HLA class I HLA-A*02:08 and *30:09, HLA-B*08:04 and *35:04 showed an association before the Bonferroni correction.
RESUMO Objetivo: Estudar a suscetibilidade genética a neuromielite óptica (NMO) assim como sua relação com o genótipo HLA na população do sul do Brasil. Métodos: Nós analisamos pacientes com NMO que preenchiam os critérios diagnósticos de Wingerchuk para NMO, com presença do anticorpo anti-AQP4-IgG no soro. O genótipo HLA foi realizado usando técnicas de alta resolução (sequenciamento de Sanger) em pacientes e controles. Genótipos HLA foram estatisticamente comparados com uma população controle pareada. Resultados: Genotipagem HLA revelou a diversidade da população sul brasileira cujo perfil HLA lembra as populações europeia e asiática. Alguns alelos tiveram correlação estatística com associação positiva (suscetibilidade aumentada) com NMO, particularmente o HLA-DRB1*04:05 e *16:02. Conclusões: Em nosso estudo, o genótipo HLA foi diferente do previamente relatado em outras populações brasileiras. Embora o número de pacientes tenha sido pequeno, HLA específicos foram associados com suscetibilidade aumentada a NMO para HLA-DRB1*04:05, *16:02. Os alelos HLA classe I HLA*02:08 e *30:09, HLA-B*08:04 e *35:04 tiveram associação antes da correção de Bonferroni.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Genes MHC Clase I/genética , Neuromielitis Óptica/genética , Genes MHC Clase II/genética , Predisposición Genética a la Enfermedad/genética , Alelos , Antígenos HLA/genética , Valores de Referencia , Brasil , Estudios de Casos y Controles , Reacción en Cadena de la Polimerasa , Frecuencia de los Genes , GenotipoRESUMEN
The brain is very sensitive to metabolic dysfunctions induced by diets high in saturated fatty acids, leading to neuroinflammation. The liraglutide has been found to have neuroprotective effects. However, its neuroprotective action in a model of palmitate-induced neuroinflammation had not yet been evaluated. Mice were intracerebroventricular (ICV) infused with palmitate and received subcutaneous liraglutide. The hippocampal dentate gyrus and CA1 regions were analyzed (morphology and inflammation-related proteins in microglia and astrocyte by confocal microscopy). Also, a real-time PCR was performed to measure the levels of tumor necrosis factor (TNF) alpha and interleukin (IL) 6. Palmitate ICV infusion resulted in pronounced inflammation response in the hippocampus, reactive microgliosis, and astrogliosis, with hypertrophied IBA1 immunoreactive microglia, increased microglial density with ameboid shape, decreased in the number of branches and junctions and increased the major histocompatibility complex (MHC) II expression. Also, we observed in the hippocampus of ICV palmitate infused mice an elevation in the pro-inflammatory cytokine levels TNFalpha and IL6. Liraglutide induced the neuroprotective microglial phenotype, characterized by an increased microglia complexity (enlarged Feret's diameter), an improved number of both cell junctions and processes, and lower circularity, accompanied by a significant reduction in TNFalpha and IL6 expressions. The study provides evidence that liraglutide may be a suitable treatment against the palmitate-induced neuroinflammation, which it is characterized by the reactive microgliosis and astrogliosis, as well as increased pro-inflammatory cytokines, which has been described as one of the primary causes of several pathologies of the central nervous system.
Asunto(s)
Hipocampo/patología , Inflamación/tratamiento farmacológico , Liraglutida/farmacología , Fármacos Neuroprotectores/farmacología , Animales , Región CA1 Hipocampal/patología , Proteínas de Unión al Calcio/metabolismo , Giro Dentado/patología , Genes MHC Clase II/genética , Gliosis/patología , Inflamación/prevención & control , Inyecciones Intraventriculares , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas de Microfilamentos/metabolismo , Microglía/efectos de los fármacos , Microglía/ultraestructura , Palmitatos , Reacción en Cadena de la Polimerasa , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The swine leukocyte antigen (SLA) complex harbors highly polymorphic gene clusters encoding glycoproteins that are involved in responses to vaccines, infectious disease, and production performance. Pigs with well-defined SLA class II genes are useful for the study of disease, immunology, and vaccines. In this study, we analyzed four SLA class II genes (SLA-DRA, SLA-DRB1, SLA-DQA, SLA-DQB1) in 22 founder Guizhou minipigs using a sequence-based typing method. Twelve alleles were detected, compared with the SLA class II allele sequences in the GenBank, and one of twelve alleles was found to be novel in Guizhou minipigs. There are four SLA II haplotypes, and one of them has been previously reported in Meishan pigs. Furthermore, based on sequence information of these alleles, we developed a simple SLA typing method implemented to SLA-typing for unknown offspring of Guizhou minipigs, relying on designed twelve sequence specific primers that could discriminate between each other. According to the combination of sequence-based typing and PCR-SSP, we were able to rapidly check SLA typing of Guizhou breeding stock and identified four SLA haplotypes in the herd. Therefore, SLA-defined Guizhou minipigs will be useful as animal models for xenotransplantation and immunological research.
Asunto(s)
Genes MHC Clase II/genética , Haplotipos/genética , Antígenos de Histocompatibilidad Clase II/genética , Polimorfismo Genético/genética , Porcinos Enanos/genética , Alelos , Animales , Cruzamiento/métodos , Antígenos de Histocompatibilidad Clase I , PorcinosRESUMEN
Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Asma/inducido químicamente , Genes MHC Clase I/genética , Genes MHC Clase II/genética , Isocianatos/toxicidad , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Asma/genética , Variación Genética , Genotipo , Enfermedades Profesionales/genética , Polimorfismo de Nucleótido Simple , RiesgoRESUMEN
Rheumatoid arthritis (RA) is a complex autoimmune disease of recent evolutionary origin. Genetic drift determines diverse polymorphisms implicated in the susceptibility to RA including the major histocompatibility complex (MHC) class II genes in the so-called shared epitope. These genes originated after the divergence between Homo and Pan from their common ancestry Ardipithecus ramidus about 5 million years ago. Natural selection determined the particular changes in the legs (bipedal position), hands, neck, brain and eusociality in humans which influence the clinical presentation of RA. In this article, we hypothesized that the origin and course of RA may be explainable in the light of evolution.
Asunto(s)
Artritis Reumatoide/genética , Artritis Reumatoide/patología , Cromosomas Humanos Par 6/genética , Evolución Molecular , Genes MHC Clase II/genética , Modelos Biológicos , Articulación Atlantoaxoidea/patología , Flujo Genético , Mano/patología , Cadera/patología , Humanos , Selección GenéticaRESUMEN
Previous studies have shown a significant association between polymorphisms of the BoLA DRB3 gene and Bovine Leukemia Virus (BLV) infection profile. The presence of allele *1501 has been associated with high proviral load in peripheral blood while allele *0902 has been associated with low proviral load. The purpose of this study was to develop allele-specific real-time PCRs to identify cattle carrying alleles associated with resistance (BoLA DRB3*0902) or susceptibility (BoLA DRB3*1501) to the BLV progression. Specific primers were designed and differential amplification was carried out by real-time PCR and monitored by SYBR® Green dye in DNA samples from peripheral blood. Conditions were also adjusted for traditional PCR amplification (end point amplification). These methods are rapid, simple and suitable for high throughput screening, and could aid in marker-assisted selection of BLV-resistant and susceptible cattle.
Asunto(s)
Leucosis Bovina Enzoótica/genética , Alelos , Animales , Bovinos/genética , Progresión de la Enfermedad , Resistencia a la Enfermedad/genética , Susceptibilidad a Enfermedades/veterinaria , Femenino , Genes MHC Clase II/genética , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad/genética , Virus de la Leucemia Bovina , Polimorfismo Genético/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Carga Viral/genéticaRESUMEN
Multiple Sclerosis (MS) is a complex disease where genetic and environmental factors have been implicated. The onset of symptoms occurs in individuals from twenty to fifty years of age, producing a progressive impairment of motor, sensory and cognitive functions. MS is more frequent in females than in males with a ratio of 4:1. The prevalence of the MS varies among ethnics groups such as Europeans, Africans and Caucasians. The estimated prevalence of MS in Puerto Rico is 42 for each 100,000 habitants, which is more than the prevalence reported for Central America and the Caribbean. In spite of this prevalence, the genetic component of MS has not been explored in order to know the alleles' expression of Puerto Rican MS patients and compare it with the allele expression in other ethnic groups. Thirty-five patients and 31 control subjects were genotyped. The allele frequencies expressed in this sample were similar to those expressed for Puerto Ricans in the National Marrow Donor Program Registry (n = 3,149). The most prevalent alleles for MS patients were HLA-DRB1*01 and *03. HLA-DQB1*04 was the most frequent in the control group and HLA-A*30, in MS patients. These findings are in agreement with published data. HLA-DQB1*04 was a marginal protector in this sample and this role has not been described before. The accuracy of the results is limited due to the sample size. After performing a statistical power analysis it showed that by increasing the sample the values would be significant.
Asunto(s)
Genes MHC Clase II/genética , Genes MHC Clase I/genética , Esclerosis Múltiple/genética , Esclerosis Múltiple/inmunología , Adulto , Alelos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puerto RicoRESUMEN
Major histocompatibility complex (MHC) molecules play vital roles in triggering adaptive immune responses and are considered the most variable molecules in vertebrates. Recently, many studies have focused on the polymorphism and evolution mode of MHC in both model and non-model organisms. Here, we analyzed the MHC class II exon 2-encoding ß chain in comparison with the mitochondrial Cytb gene and our previously published microsatellite data set in three cultured stocks and four wild populations of the orange-spotted grouper (Epinephelus coioides) in order to investigate its genetic variation and mechanism of evolution. We detected one to four alleles in one individual, suggesting that at least two loci exist in the orange-spotted grouper, as well as a particularly high level of allelic diversity at the MHC loci. Furthermore, the cultured stocks exhibited reduced allelic diversity compared to the wild counterparts. We found evidence of balancing selection at MHC class II exon 2, and codon sites under positive selection were largely correspondent to the protein-binding region. In addition, MHC class II exon 2 revealed significant differences between population differentiation patterns from the neutral mitochondrial Cytb and microsatellites, which may indicate local adaptation at MHC loci in orange-spotted grouper originating from the South China Sea and Southeast Asia.
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Animales Salvajes/genética , Lubina/crecimiento & desarrollo , Lubina/genética , Exones/genética , Genes MHC Clase II/genética , Variación Genética , Selección Genética , Animales , Animales Salvajes/crecimiento & desarrollo , Asia Sudoriental , China , Citocromos b/genética , Genética de Población , Geografía , Antígenos de Histocompatibilidad Clase II/genética , Funciones de Verosimilitud , Mitocondrias/genética , Datos de Secuencia Molecular , Filogenia , Pigmentación/genéticaRESUMEN
We estimated levels of diversity at the major histocompatibility complex (MHC) class II DRß1 gene in 50 breeding pairs of the Magellanic penguin and compared those to estimates from Humboldt and Galapagos penguins. We tested for positive selection and 2 conditions required for the evolution of MHC-based disassortative mating: 1) greater MHC diversity between breeding pairs compared to random mating, and 2) associations between MHC genotype and fitness. Cloning and sequencing of the DRß1 gene showed that Magellanic penguins had higher levels of genetic variation than Galapagos and Humboldt penguins. Sequence analysis revealed 45 alleles with 3.6% average proportion of nucleotide differences, nucleotide diversity of 0.030, and observed heterozygosity of 0.770. A gene phylogeny showed 9 allelic lineages with interspersed DRß1 sequences from Humboldt and Galapagos penguins, indicating ancestral polymorphisms. d (N)/d (S) ratios revealed evidence for positive selection. Analysis of breeding pairs showed no disassortative mating preferences. Significant MHC genotype/fitness associations in females suggest, however, that selection for pathogen resistance plays a more important role than mate choice in maintaining diversity at the MHC in the Magellanic penguin. The differential effect of MHC heterozygosity on fitness between the sexes is likely associated with the relative role of hatching and fledging rates as reliable indicators of overall fitness in males and females.
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Variación Genética , Complejo Mayor de Histocompatibilidad/genética , Conducta Sexual Animal/fisiología , Spheniscidae/genética , Animales , Argentina , Femenino , Genes MHC Clase II/genética , Genética de Población , Cadenas HLA-DRB1/genética , Heterocigoto , Masculino , Datos de Secuencia Molecular , Filogenia , Polimorfismo Genético , Análisis de Regresión , Selección Genética , Programas InformáticosRESUMEN
This study explored the use of the gene encoding the ß subunit of the major histocompatibility (MH) receptor as a population marker in Arctic charr Salvelinus alpinus. The use of this polymorphic marker allowed differentiation of the S. alpinus lineages previously defined using mitochondrial DNA (mtDNA) but also allowed differentiation between the populations studied within those lineages. The majority of the variation observed here occurred prior to the last glaciation event. Nevertheless, all S. alpinus populations were differentiated using both MH Class II ß (mh-IIß) sequences and allelic frequencies. The fact that all the populations studied presented high rates of non-synonymous: synonymous substitutions and high levels of interpopulation variation, suggested mh-IIß as an ideal marker to assess differentiation among S. alpinus populations in ways that may represent divergence both by genetic drift and natural adaptation to the local environment.
Asunto(s)
Genes MHC Clase II/genética , Polimorfismo Genético , Trucha/genética , Secuencia de Aminoácidos , Animales , ADN Mitocondrial/genética , Frecuencia de los Genes , Variación Genética , Genética de Población , Datos de Secuencia Molecular , Filogenia , Alineación de Secuencia , Trucha/clasificaciónRESUMEN
Population studies represent an integral part and link in understanding the complex chain of host-pathogen interactions, disease pathogenesis, and MHC gene polymorphisms. Genes of Mongoloid, Caucasoid, and Negroid populations have created a distinctive HLA genetic profile in the Venezuelan population. Our objective was to determine the predominant HLA class I and II alleles and haplotype frequencies in the hybrid population of Venezuela. The study population consisted of 486 healthy unrelated native Venezuelans and 180 families. We examined the frequency of HLA A-B-C, HLA-DQ and HLA-DR genes by polymerase chain reaction and subsequent hybridization with sequence-specific oligonucleotide probes. Phenotypic, allelic and haplotype frequencies were estimated by direct counting and using the maximum-likelihood method. The predominant HLA class I alleles were A*02, A*24, A*68, B*35, B*44, B*51, B*07, B*15 and Cw*07. Regarding HLA class II, the most frequent alleles were DQB1*03 and DRB1*04, DRB1*15, DRB1*13, DRB1*07. The prevailing haplotype was HLA-A*02B*35 DQB1*03 DRB1*04. Some of these alleles and haplotype frequencies were predominantly present in Amerindians (A*02, A*24, B*35, Cw*07, DRB1*04, A*24 B*35). Previous reports have shown high incidence of A*02, B*44, B*51, DRB1*15, DRB1*13, DRB1*07 alleles in several European populations and A*68, B*07, B*15 alleles in African Americans, which could have contributed to the ethnic admixture of the Venezuelan population. We conclude that our results provide strong evidence that Venezuela's population represents an admixture of the primitive Mongoloid Aborigines, Caucasoid Europeans and Western African Negroid migrants.
Asunto(s)
Genes MHC Clase II/genética , Genes MHC Clase I/genética , Alelos , Etnicidad/genética , Etnicidad/estadística & datos numéricos , Frecuencia de los Genes , Genética de Población , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Haplotipos , Prueba de Histocompatibilidad , Humanos , Venezuela/epidemiologíaRESUMEN
Immune surveillance in the central nervous system (CNS) was considered impossible because: (i) the brain parenchyma is separated from the blood circulation by the blood-brain barrier (BBB); (ii) the brain lacks lymphatic drainage and (iii) the brain displays low major histocompatibility complex class II (MHCII) expression. In this context, the BBB prevents entry of immune molecules and effector cells to the CNS. The absence of lymphatic vessels avoids CNS antigens from reaching the lymph nodes for lymphocyte presentation and activation. Finally, the low MHCII expression hinders effective antigen presentation and re-activation of T cells for a competent immune response. All these factors limit the effectiveness of the afferent and efferent arms necessary to carry out immune surveillance. Nevertheless, recent evidence supports that CNS is monitored by the immune system through a modified surveillance circuit; this work reviews these findings.
Asunto(s)
Sistema Nervioso Central/inmunología , Vigilancia Inmunológica/inmunología , Vigilancia Inmunológica/fisiología , Neuroinmunomodulación/fisiología , Animales , Presentación de Antígeno , Antígenos/análisis , Antígenos/inmunología , Barrera Hematoencefálica/inmunología , Barrera Hematoencefálica/fisiología , Movimiento Celular , Genes MHC Clase II/genética , Humanos , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/fisiología , Sistema Linfático/fisiología , Esclerosis Múltiple/inmunologíaRESUMEN
Genes of the major histocompatibility complex (MHC) have a crucial role in the immune response of vertebrates, alter the individual odour and are involved in shaping mating preferences. Pathogen-mediated selection, sexual selection and maternal-fetal interactions have been proposed as the main drivers of frequently observed high levels of polymorphism in functionally important parts of the MHC. Bats constitute the second largest mammalian order and have recently emerged as important vectors of infectious diseases. In addition, Chiroptera are interesting study subjects in evolutionary ecology in the context of olfactory communication, mate choice and associated fitness benefits. Thus, it is surprising that they belong to the least studied mammalian taxa in terms of their MHC diversity. In this study, we investigated the variability in the functionally important MHC class II gene DRB, evidence for selection and population structure in the group-living lesser bulldog bat, Noctilio albiventris, in Panama. We found a single expressed, polymorphic Noal-DRB gene. The substitution pattern of the nucleotide sequences of the 18 detected alleles provided evidence for positive selection acting above the evolutionary history of the species in shaping MHC diversity. Roosting colonies were not genetically differentiated but females showed lower levels of heterozygosity than males, which might be a sign that the sexes differ in the selection pressures acting on the MHC. This study provides the prerequisites for further investigations of the role of the individual MHC constitution in parasite resistance, olfactory communication and mate choice in N. albiventris and other bats.