RESUMO
Specific interactions of host and parasite genotypes can lead to balancing selection, maintaining genetic diversity within populations. In order to understand the drivers of such specific coevolution, it is necessary to identify the molecular underpinnings of these genotypic interactions. Here, we investigate the genetic basis of resistance in the crustacean host, Daphnia magna, to attachment and subsequent infection by the bacterial parasite, Pasteuria ramosa. We discover a single locus with Mendelian segregation (3:1 ratio) with resistance being dominant, which we call the F locus. We use QTL analysis and fine mapping to localize the F locus to a 28.8-kb region in the host genome, adjacent to a known resistance supergene. We compare the 28.8-kb region in the two QTL parents to identify differences between host genotypes that are resistant versus susceptible to attachment and infection by the parasite. We identify 13 genes in the region, from which we highlight eight biological candidates for the F locus, based on presence/absence polymorphisms and differential gene expression. The top candidates include a fucosyltransferase gene that is only present in one of the two QTL parents, as well as several Cladoceran-specific genes belonging to a large family that is represented in multiple locations of the host genome. Fucosyltransferases have been linked to resistance in previous studies of Daphnia-Pasteuria and other host-parasite systems, suggesting that P. ramosa spore attachment could be mediated by changes in glycan structures on D. magna cuticle proteins. The Cladoceran-specific candidate genes suggest a resistance strategy that relies on gene duplication. Our results add a new locus to a growing genetic model of resistance in the D. magna-P. ramosa system. The identified candidate genes will be used in future functional genetic studies, with the ultimate aim to test for cycles of allele frequencies in natural populations.
Assuntos
Daphnia , Resistência à Doença , Interações Hospedeiro-Patógeno , Pasteuria , Animais , Daphnia/genética , Daphnia/microbiologia , Genoma , Genótipo , Interações Hospedeiro-Patógeno/genética , Modelos Biológicos , Pasteuria/genética , Polimorfismo Genético , Resistência à Doença/genéticaRESUMO
The vertebrate adaptive immune systems (Agnatha and Gnathostomata) use sets of T and B lymphocyte lineages that somatically generate highly diverse repertoires of Ag-specific receptors and Abs. In Gnathostomata, cytokine networks regulate the activation of lymphoid and myeloid cells, whereas little is known about these components in Agnathans. Most gnathostome cytokines are four-helix bundle cytokines with poorly conserved primary sequences. In contrast, sequence conservation across bilaterians has been observed for cognate cytokine receptor chains, allowing their structural classification into two classes, and for downstream JAK/STAT signaling mediators. With conserved numbers among Gnathostomata, human cytokine receptor chains (comprising 34 class I and 12 class II) are able to interact with 28 class I helical cytokines (including most ILs) and 16 class II cytokines (including all IFNs), respectively. Hypothesizing that the arsenal of cytokine receptors and transducers may reflect homologous cytokine networks, we analyzed the lamprey genome and transcriptome to identify genes and transcripts for 23 class I and five class II cytokine receptors alongside one JAK signal mediator and four STAT transcription factors. On the basis of deduction of their respective orthologs, we predict that these receptors may interact with 16 class I and 3 class II helical cytokines (including IL-4, IL-6, IL-7, IL-12, IL-10, IFN-γ, and thymic stromal lymphoprotein homologs). On the basis of their respective activities in mammals, this analysis suggests the existence of lamprey cytokine networks that may regulate myeloid and lymphoid cell differentiation, including potential Th1/Th2 polarization. The predicted networks thus appear remarkably homologous to those of Gnathostomata, albeit reduced to essential functions.
Assuntos
Interleucina-10 , Receptores de Citocinas , Animais , Citocinas/metabolismo , Humanos , Interleucina-12 , Interleucina-4 , Interleucina-6 , Interleucina-7 , Lampreias , Mamíferos/metabolismo , Receptores de Citocinas/genética , Fatores de Transcrição STAT , Vertebrados/metabolismoRESUMO
NKp30 is an activating natural killer cell receptor (NKR) with a single-exon variable (VJ)-type immunoglobulin superfamily (IgSF) domain. Such VJ-IgSF domains predate the emergence of the antigen receptors (immunoglobulin and T cell receptor), which possess the same domain but undergo gene rearrangement. NCR3, the gene encoding NKp30, is present in jawed vertebrates from sharks to mammals; thus, unlike most NKR that are highly divergent among vertebrate taxa, NKp30 is uniquely conserved. We previously hypothesized that an ancestral NCR3 gene was encoded in the proto-major histocompatibility complex (MHC), the region where many immune-related genes have accumulated. Herein, we searched in silico databases to identify NCR3 paralogues and examined their genomic locations. We found a paralogue, NCR3H, in many vertebrates but was lost in mammals. Additionally, we identified a set of voltage-gated sodium channel beta (SCNB) genes as NCR3-distantly-related genes. Like NCR3, both NCR3H and SCNB proteins contain a single VJ-IgSF domain followed by a transmembrane region. These genes map to MHC paralogous regions, originally described in an invertebrate, along with genes encoding cell adhesion molecules involved in NK cell recognition networks. Other genes having no obvious relationship to immunity also map to these paralogous regions. These gene complexes were traced to several invertebrates, suggesting that the foundation of these cellular networks emerged before the genome-wide duplications in early gnathostome history. Here, we propose that this ancestral region was involved in cell-mediated immunity prior to the emergence of adaptive immunity and that NCR3 piggybacked onto this primordial complex, heralding the emergence of vertebrate NK cell/T cells.
Assuntos
Receptores de Antígenos de Linfócitos T , Vertebrados , Animais , Vertebrados/genética , Receptores de Antígenos de Linfócitos T/genética , Imunidade Celular/genética , Genômica , Imunoglobulinas/genética , Mamíferos , FilogeniaRESUMO
Immunological memory is one of the core topics of contemporary immunology. Yet there are many discussions about what this concept precisely means, which components of the immune system display it, and in which phyla it exists. Recent years have seen the multiplication of claims that immunological memory can be found in "innate" immune cells and in many phyla beyond vertebrates (including invertebrates, plants, but also bacteria and archaea), as well as the multiplication of concepts to account for these phenomena, such as "innate immune memory" or "trained immunity". The aim of this critical review is to analyze these recent claims and concepts, and to distinguish ideas that have often been misleadingly associated, such as memory, adaptive immunity, and specificity. We argue that immunological memory is a gradual and multidimensional phenomenon, irreducible to any simple dichotomy, and we show why adopting this new view matters from an experimental and therapeutic point of view.
Assuntos
Imunidade Adaptativa , Memória Imunológica , Animais , Evolução Biológica , Interações Hospedeiro-Patógeno/imunologia , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismoRESUMO
Knowledge of the genetic architecture of pathogen infectivity and host resistance is essential for a mechanistic understanding of coevolutionary processes, yet the genetic basis of these interacting traits remains unknown for most host-pathogen systems. We used a comparative genomic approach to explore the genetic basis of infectivity in Pasteuria ramosa, a Gram-positive bacterial pathogen of planktonic crustaceans that has been established as a model for studies of Red Queen host-pathogen coevolution. We sequenced the genomes of a geographically, phenotypically, and genetically diverse collection of P. ramosa strains and performed a genome-wide association study to identify genetic correlates of infection phenotype. We found multiple polymorphisms within a single gene, Pcl7, that correlate perfectly with one common and widespread infection phenotype. We then confirmed this perfect association via Sanger sequencing in a large and diverse sample set of P. ramosa clones. Pcl7 codes for a collagen-like protein, a class of adhesion proteins known or suspected to be involved in the infection mechanisms of a number of important bacterial pathogens. Consistent with expectations under Red Queen coevolution, sequence variation of Pcl7 shows evidence of balancing selection, including extraordinarily high diversity and absence of geographic structure. Based on structural homology with a collagen-like protein of Bacillus anthracis, we propose a hypothesis for the structure of Pcl7 and the physical location of the phenotype-associated polymorphisms. Our results offer strong evidence for a gene governing infectivity and provide a molecular basis for further study of Red Queen dynamics in this model host-pathogen system.
Assuntos
Coevolução Biológica , Interações Hospedeiro-Patógeno/genética , Pasteuria/genética , Proteínas de Bactérias/química , Genes Bacterianos , Estudo de Associação Genômica Ampla , Glicosilação , Pasteuria/patogenicidade , Polimorfismo de Nucleotídeo Único , Estrutura Quaternária de ProteínaRESUMO
Negative frequency-dependent selection (NFDS) is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa. We fine-map one locus associated with D. magna resistance to P. ramosa and genetically characterize two haplotypes of the Pasteuria resistance (PR-) locus using de novo genome and transcriptome sequencing. Sequence comparison of PR-locus haplotypes finds dramatic structural polymorphisms between PR-locus haplotypes including a large portion of each haplotype being composed of non-homologous sequences resulting in haplotypes differing in size by 66 kb. The high divergence of PR-locus haplotypes suggest a history of multiple, diverse and repeated instances of structural mutation events and restricted recombination. Annotation of the haplotypes reveals striking differences in gene content. In particular, a group of glycosyltransferase genes that is present in the susceptible but absent in the resistant haplotype. Moreover, in natural populations, we find that the PR-locus polymorphism is associated with variation in resistance to different P. ramosa genotypes, pointing to the PR-locus polymorphism as being responsible for the matching-allele interactions that have been previously described for this system. Our results conclusively identify a genetic basis for the matching-allele interaction observed in a coevolving host-parasite system and provide a first insight into its molecular basis.
Assuntos
Daphnia/genética , Interações Hospedeiro-Parasita/genética , Pasteuria/genética , Seleção Genética/genética , Alelos , Animais , Daphnia/microbiologia , Evolução Molecular , Variação Genética , Genótipo , Haplótipos/genética , Pasteuria/patogenicidade , Polimorfismo GenéticoRESUMO
Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.
Assuntos
Artrópodes/genética , Genoma , Sintenia , Animais , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/genética , Metilação de DNA , Evolução Molecular , Feminino , Genoma Mitocondrial , Hormônios/genética , Masculino , Família Multigênica , Filogenia , Polimorfismo Genético , Proteínas Quinases/genética , RNA não Traduzido/genética , Receptores Odorantes/genética , Selenoproteínas/genética , Cromossomos Sexuais , Fatores de Transcrição/genéticaRESUMO
The MHC is a large genetic region controlling Ag processing and recognition by T lymphocytes in vertebrates. Approximately 40% of its genes are implicated in innate or adaptive immunity. A putative proto-MHC exists in the chordate amphioxus and in the fruit fly, indicating that a core MHC region predated the emergence of the adaptive immune system in vertebrates. In this study, we identify a putative proto-MHC with archetypal markers in the most basal branch of Metazoans--the placozoan Trichoplax adhaerens, indicating that the proto-MHC is much older than previously believed--and present in the common ancestor of bilaterians (contains vertebrates) and placozoans. Our evidence for a T. adhaerens proto-MHC was based on macrosynteny and phylogenetic analyses revealing approximately one third of the multiple marker sets within the human MHC-related paralogy groups have unique counterparts in T. adhaerens, consistent with two successive whole genome duplications during early vertebrate evolution. A genetic ontologic analysis of the proto-MHC markers in T. adhaerens was consistent with its involvement in defense, showing proteins implicated in antiviral immunity, stress response, and ubiquitination/proteasome pathway. Proteasome genes psma, psmb, and psmd are present, whereas the typical markers of adaptive immunity, such as MHC class I and II, are absent. Our results suggest that the proto-MHC was involved in intracellular intrinsic immunity and provide insight into the primordial architecture and functional landscape of this region that later in evolution became associated with numerous genes critical for adaptive immunity in vertebrates.
Assuntos
Imunidade Adaptativa/genética , Complexo Principal de Histocompatibilidade/genética , Placozoa/genética , Placozoa/imunologia , Animais , Evolução Biológica , Genoma , Humanos , Complexo Principal de Histocompatibilidade/imunologia , Fatores de Crescimento Neural/genética , Filogenia , Complexo de Endopeptidases do Proteassoma/genética , Estresse Fisiológico/genética , Linfócitos T/imunologia , Ubiquitinação/genéticaRESUMO
Sharks and skates represent the earliest vertebrates with an adaptive immune system based on lymphocyte Ag receptors generated by V(D)J recombination. Shark B cells express two classical Igs, IgM and IgW, encoded by an early, alternative gene organization consisting of numerous autonomous miniloci, where the individual gene cluster carries a few rearranging gene segments and one C region, µ or ω. We have characterized eight distinct Ig miniloci encoding the nurse shark ω H chain. Each cluster consists of VH, D, and JH segments and six to eight C domain exons. Two interspersed secretory exons, in addition to the 3'-most C exon with tailpiece, provide the gene cluster with the ability to generate at least six secreted isoforms that differ as to polypeptide length and C domain combination. All clusters appear to be functional, as judged by the capability for rearrangement and absence of defects in the deduced amino acid sequence. We previously showed that IgW VDJ can perform isotype switching to µ C regions; in this study, we found that switching also occurs between ω clusters. Thus, C region diversification for any IgW VDJ can take place at the DNA level by switching to other ω or µ C regions, as well as by RNA processing to generate different C isoforms. The wide array of pathogens recognized by Abs requires different disposal pathways, and our findings demonstrate complex and unique pathways for C effector function diversity that evolved independently in cartilaginous fishes.
Assuntos
Genes de Imunoglobulinas/genética , Switching de Imunoglobulina/genética , Isotipos de Imunoglobulinas/genética , RNA/genética , Tubarões/genética , Tubarões/imunologia , Animais , Sequência de Bases , Southern Blotting , Genes de Imunoglobulinas/imunologia , Switching de Imunoglobulina/imunologia , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Isotipos de Imunoglobulinas/imunologia , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
« Prediction is very difficult, especially if it is about the future of comparative immunology" could one say to paraphrase Niels Bohr. Yet, if one avoids mistakes of the past and fashions, if one remains ready to welcome surprises an do not to get drowned in big data while profiting from new technologies, if one keeps common sense between expanding and restricting one's scope of investigation in front of the enormous diversity of the tree of life, comparative immunologists are going, in new areas of research and with new tools, to keep contributing enormously to immunology. They will reveal, with the eyes open to homologies and analogies among multiple species, more variations on the theme of immunity and will put the human immune system in perspective a necessary situation to face the questions that remain to be answered in order to improve health or to understand evolution of immune systems. There will always be room in comparative immunology for fundamental approaches to these subjects. A proper education, aimed at combining competences, will be essential to achieve these goals.
RESUMO
Balancing selection is an evolutionary process that maintains genetic polymorphisms at selected loci and strongly reduces the likelihood of allele fixation. When allelic polymorphisms that predate speciation events are maintained independently in the resulting lineages, a pattern of trans-species polymorphisms may occur. Trans-species polymorphisms have been identified for loci related to mating systems and the MHC, but they are generally rare. Trans-species polymorphisms in disease loci are believed to be a consequence of long-term host-parasite coevolution by balancing selection, the so-called Red Queen dynamics. Here we scan the genomes of three crustaceans with a divergence of over 15 million years and identify 11 genes containing identical-by-descent trans-species polymorphisms with the same polymorphisms in all three species. Four of these genes display molecular footprints of balancing selection and have a function related to immunity. Three of them are located in or close to loci involved in resistance to a virulent bacterial pathogen, Pasteuria, with which the Daphnia host is known to coevolve. This provides rare evidence of trans-species polymorphisms for loci known to be functionally relevant in interactions with a widespread and highly specific parasite. These findings support the theory that specific antagonistic coevolution is able to maintain genetic diversity over millions of years.
Assuntos
Daphnia , Polimorfismo Genético , Seleção Genética , Animais , Daphnia/genética , Daphnia/microbiologia , Daphnia/imunologia , Pasteuria/genética , Pasteuria/patogenicidade , Resistência à Doença/genética , Crustáceos/genética , Crustáceos/microbiologia , Crustáceos/imunologia , Evolução Molecular , Genoma/genética , Filogenia , AlelosRESUMO
A fundamental tenet of immunology is that adaptive immune responses are initiated in secondary lymphoid tissues. This dogma has been challenged by several recent reports. We discuss how successful T cell-mediated immunity can be initiated outside of such dedicated structures, whereas they are required for adaptive humoral immunity. This resembles an ancient immune pathway in the oldest cold-blooded vertebrates, which lack lymph nodes and sophisticated B-cell responses including optimal affinity maturation. The T-cell, however, has retained the capacity to recognize antigen in a lymph node-free environment. Besides bone marrow and lung, the liver is one organ that can potentially serve as a surrogate lymphoid organ and could represent a remnant from the time before lymph nodes developed.
Assuntos
Linfócitos B/imunologia , Evolução Biológica , Tecido Linfoide/imunologia , Linfócitos T/imunologia , Imunidade Adaptativa , Animais , Imunidade InataRESUMO
Since an immunoreceptor tyrosine-based inhibition motif (ITIM) was first identified in the intracytoplasmic domain of Fc gammaRIIB, ITIMs have been found in a large number of inhibitory molecules that were shown to negatively regulate cell activation. Due to their wide tissue distribution and to the variety of their extracellular ligands, ITIM-containing molecules are involved in the control of a large spectrum of biological functions, mostly but not exclusively related to immunity. On the basis of sequence comparison, ITIMs were structurally defined as 6-amino acid sequences containing a tyrosine (Y) with loosely conserved N-terminal (Y-2) and C-terminal (Y+3) residues. Molecular analysis of signaling events demonstrated that when coaggregated with activating receptors, ITIMs are phosphorylated by Src-family tyrosine kinases, which enables them to recruit Src homology 2 domain-containing phosphatases that antagonize activation signals. Because ITIM-dependent negative regulation seems to be a fundamental regulatory mechanism, both in rodents and in humans, and because it can be used either as a target or as a powerful tool in various diseases, we undertook (i) a genome-wide search of potential novel ITIM-containing molecules in humans, mice, frogs, birds, and flies and (ii) a comparative analysis of potential ITIMs in major animal phyla, from mammals to protozoa. We found a surprisingly high number of potential ITIM-containing molecules, having a great diversity of extracellular domains, and being expressed by a variety of immune and non-immune cells. ITIMs could be traced back to the most primitive metazoa. The genes that encode ITIM-containing molecules that belong to the immunoglobulin superfamily or to the C-lectin family seem to derive from a common set of ancestor genes and to have dramatically expanded and diverged in Gnathostomata (from fish to mammals).
Assuntos
Motivos de Aminoácidos/imunologia , Receptores Imunológicos/imunologia , Transdução de Sinais/imunologia , Domínios de Homologia de src/imunologia , Quinases da Família src/imunologia , Animais , Evolução Molecular , Retroalimentação Fisiológica , Humanos , Receptores de IgG/genética , Receptores de IgG/imunologia , Receptores de IgG/metabolismo , Receptores Imunológicos/genéticaRESUMO
The degree of specificity in host-parasite interactions has important implications for ecology and evolution. Unfortunately, specificity can be difficult to determine when parasites cannot be cultured. In such cases, studies often use isolates of unknown genetic composition, which may lead to an underestimation of specificity. We obtained the first clones of the unculturable bacterium Pasteuria ramosa, a parasite of Daphnia magna. Clonal genotypes of the parasite exhibited much more specific interactions with host genotypes than previous studies using isolates. Clones of P. ramosa infected fewer D. magna genotypes than isolates and host clones were either fully susceptible or fully resistant to the parasite. Our finding enhances our understanding of the evolution of virulence and coevolutionary dynamics in this system. We recommend caution when using P. ramosa isolates as the presence of multiple genotypes may influence the outcome and interpretation of some experiments.
Assuntos
Daphnia/genética , Daphnia/microbiologia , Variação Genética , Pasteuria/genética , Animais , Técnicas Bacteriológicas , Evolução Biológica , Europa (Continente) , Genótipo , Interações Hospedeiro-Patógeno , Pasteuria/patogenicidade , Especificidade da Espécie , VirulênciaRESUMO
The stat gene family diversified during early vertebrate evolution thanks to two rounds of whole genome duplication (WGD) to produce a typical repertoire composed of 6 STAT factors (named 1-6). In contrast, only one or two stat genes have been reported in C. elegans and in D. melanogaster. The main types of STAT found from bony fish to mammals are present in Agnathan genomes, but a typical STAT1-6 repertoire is only observed in jawed vertebrates. Comparative syntenies showed that STAT6 was the closest to the ancestor of the family. An extensive survey of stat genes across fish including polyploid species showed that whole genome duplications did not lead to a uniform expansion of stat genes. While 2 to 5 stat1 are present in salmonids, whose genome duplicated about 35My ago, only one copy of stat2 and stat6 is retained. In contrast, common carp, with a recent whole genome duplication (5-10My), possesses a doubled stat repertoire indicating that the elimination of stat2 and stat6 additional copies is not immediate. Altogether our data shed light on the multiplicity of evolutionary pathways followed by key components of the canonical cytokine receptor signalling pathway, and point to differential selective constraints exerted on these factors.
Assuntos
Peixes/genética , Fatores de Transcrição STAT/genética , Animais , Evolução Molecular , Peixes/classificação , Peixes/imunologia , Duplicação Gênica , Expressão Gênica/imunologia , Variação Genética , Genoma , Família Multigênica , Filogenia , Receptores de Citocinas , Transdução de Sinais/genética , Sintenia , Vertebrados/classificação , Vertebrados/genética , Vertebrados/imunologiaRESUMO
Members of the Toll-like receptor (TLR) and the interleukin 1 receptor (IL1R) superfamilies activate various signaling cascades that are evolutionarily conserved in eumetazoans. In this study, we have searched the genome and expressed sequence tags of the demosponge Amphimedon queenslandica for molecules involved in TLR and IL1R signaling. Although we did not identify a conventional TLR or ILR, the Amphimedon genome encodes two related receptors, AmqIgTIRs, which are comprised of at least three extracellular IL1R-like immunoglobulins (Ig) and an intracellular TLR-like Toll/interleukin1 receptor/resistance (TIR) domain. The remainder of the TLR/IL1R pathway is mostly conserved in Amphimedon and includes genes known to interact with TLRs and IL1Rs in bilaterians, such as Toll-interacting protein (Tollip) and myeloid differentiation factor 88 (MyD88). By comparing the sponge genome to that of nonmetazoan eukaryotes and other basal animal phyla (i.e., placozoan and cnidarian representatives) we can infer that most components of the signaling cascade, including the receptors, evolved after the divergence of metazoan, and choanoflagellate lineages. In most cases, these proteins are composed of metazoan-specific domains (e.g., Pellino) or architectures (e.g., the association of a death domain with a TIR domain in the MyD88). The dynamic expression of the two AmqIgTIRs, AmqMyD88, AmqTollip, and AmqPellino during Amphimedon embryogenesis and larval development is consistent with the TLR/IL1R pathway having a role in both development and immunity in the last common metazoan ancestor.
Assuntos
Genoma , Poríferos/genética , Receptores de Interleucina-1/genética , Transdução de Sinais , Receptores Toll-Like/genética , Sequência de Aminoácidos , Animais , Evolução Biológica , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/genética , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Modelos Genéticos , Dados de Sequência Molecular , Poríferos/embriologia , Estrutura Terciária de Proteína , Receptores de Interleucina-1/química , Alinhamento de Sequência , Receptores Toll-Like/químicaRESUMO
In mammals, T cell activation requires specific recognition of the peptide-MHC complex by the TcR and co-stimulatory signals. Important co-stimulatory receptors expressed by T cells are the molecules of the CD28 family, that regulate T cell activation, proliferation and tolerance. These receptors recognize B7s and B7-homologous (B7H) molecules that are typically expressed by the antigen presenting cells. In teleost fish, typical T cell responses have been described and the TcR, MHC and CD28/CTLA4 genes have been characterized. In contrast, the members of the B7 gene family have only been described in mammals and birds and have yet to be addressed in lower vertebrates. To learn more about the evolution of components guiding T cell activation in vertebrates, we performed a systematic genomic survey for the B7 co-stimulatory and co-inhibitory IgSF receptors in lower vertebrates with an emphasis on teleost fish. Our search identified fish sequences that are orthologous to B7, B7-H1/B7-DC, B7-H3 and B7-H4 as defined by sequence identity, phylogeny and combinations of short or long-range syntenic relationships. However, we were unable to identify clear orthologs for B7-H2 (CD275, ICOS ligand) in bony fish, which correlates with our prior inability to find ICOS in fish. Interestingly, our results indicate that teleost fish possess a single B7.1/B7.2 (CD80/86) molecule that likely interacts with CD28/CTLA4 as the ligand-binding regions seem to be conserved in both partners. Overall, our analyses implies that gene duplication (and loss) have shaped a molecular repertoire of B7-like molecules that was recruited for the refinement of T cell activation during the evolution of the vertebrates.
Assuntos
Antígenos CD28/genética , Antígenos CD28/imunologia , Evolução Molecular , Sequência de Aminoácidos , Animais , Antígeno B7-1/química , Antígenos CD28/química , Sequência Conservada , Peixes/imunologia , Ligação Genética , Humanos , Modelos Imunológicos , Dados de Sequência Molecular , Filogenia , Proteína 2 Ligante de Morte Celular Programada 1 , Alinhamento de Sequência , Análise de Sequência de Proteína , SinteniaRESUMO
In insects, the homologue of the Down syndrome cell adhesion molecule (Dscam) is a unique case of a single-locus gene whose expression has extensive somatic diversification in both the nervous and immune systems. How this situation evolved is best understood through comparative studies. We describe structural, expression, and evolutionary aspects of a Dscam homolog in 2 species of the crustacean Daphnia. The Dscam of Daphnia generates up to 13,000 different transcripts by the alternative splicing of variable exons. This extends the taxonomic range of a highly diversified Dscam beyond the insects. Additionally, we have identified 4 alternative forms of the cytoplasmic tail that generate isoforms with or without inhibitory or activating immunoreceptor tyrosine-based motifs (ITIM and ITAM respectively), something not previously reported in insect's Dscam. In Daphnia, we detected exon usage variability in both the brain and hemocytes (the effector cells of immunity), suggesting that Dscam plays a role in the nervous and immune systems of crustaceans, as it does in insects. Phylogenetic analysis shows a high degree of amino acid conservation between Daphnia and insects except in the alternative exons, which diverge greatly between these taxa. Our analysis shows that the variable exons diverged before the split of the 2 Daphnia species and is in agreement with the nearest-neighbor model for the evolution of the alternative exons. The genealogy of the Dscam gene family from vertebrates and invertebrates confirmed that the highly diversified form of the gene evolved from a nondiversified form before the split of insects and crustaceans.
Assuntos
Processamento Alternativo , Daphnia/genética , Insetos/genética , Proteínas de Membrana/genética , Sequência de Aminoácidos , Animais , Química Encefálica , Moléculas de Adesão Celular , Sequência Conservada/genética , Daphnia/anatomia & histologia , Daphnia/fisiologia , Evolução Molecular , Éxons , Hemócitos/química , Humanos , Proteínas de Insetos/genética , Insetos/anatomia & histologia , Insetos/fisiologia , Dados de Sequência Molecular , Filogenia , Isoformas de Proteínas/genética , Alinhamento de SequênciaRESUMO
Two selected receptor genes of the immunoglobulin superfamily (IgSF), one CTX/JAM family member, and one poliovirus receptor-like nectin that have features of adhesion molecules can be expressed by Ciona hemocytes, the effectors of immunity. They can also be expressed in the nervous system (CTX/JAM) and in the ovary (nectin). The genes encoding these receptors are located among one set of genes, spread over Ciona chromosomes 4 and 10, and containing other IgSF members homologous to those encoded by genes present in a tetrad of human (1, 3 + X, 11, 21 + 19q) or bird chromosomes (1, 4, 24, 31) that include the leukocyte receptor complex. It is proposed that this tetrad is due to the two rounds of duplication that affected a single prevertebrate ancestral region containing a primordial leukocyte receptor complex involved in immunity and other developmental regulatory functions.
Assuntos
Evolução Molecular , Filogenia , Receptores Imunológicos/genética , Vertebrados/genética , Sequência de Aminoácidos , Animais , Moléculas de Adesão Celular/genética , Galinhas/genética , Mapeamento Cromossômico , Ciona intestinalis/embriologia , Ciona intestinalis/genética , Ciona intestinalis/crescimento & desenvolvimento , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Hemócitos/metabolismo , Antígenos de Histocompatibilidade Classe I/genética , Hibridização In Situ , Moléculas de Adesão Juncional , Leucócitos/imunologia , Leucócitos/metabolismo , Masculino , Dados de Sequência Molecular , Nectinas , Receptores Imunológicos/classificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Sintenia , Urocordados/embriologia , Urocordados/genética , Urocordados/crescimento & desenvolvimento , Vertebrados/classificação , Vertebrados/imunologiaRESUMO
Stable integration of foreign DNA into the frog genome has been the purpose of several studies aimed at generating transgenic animals or producing mutations of endogenous genes. Inserting DNA into a host genome can be achieved in a number of ways. In Xenopus, different strategies have been developed which exhibit specific molecular and technical features. Although several of these technologies were also applied in various model organizms, the attributes of each method have rarely been experimentally compared. Investigators are thus confronted with a difficult choice to discriminate which method would be best suited for their applications. To gain better understanding, a transgenesis workshop was organized by the X-omics consortium. Three procedures were assessed side-by-side, and the results obtained are used to illustrate this review. In addition, a number of reagents and tools have been set up for the purpose of gene expression and functional gene analyses. This not only improves the status of Xenopus as a powerful model for developmental studies, but also renders it suitable for sophisticated genetic approaches. Twenty years after the first reported transgenic Xenopus, we review the state of the art of transgenic research, focusing on the new perspectives in performing genetic studies in this species.