RESUMO
Cetaceans represent a natural experiment within the tree of life in which a lineage changed from terrestrial to aquatic habitats. This shift involved phenotypic modifications, representing an opportunity to explore the genetic bases of phenotypic diversity. Among the different molecular systems that maintain cellular homeostasis, ion channels are crucial for the proper physiological functioning of all living species. This study aims to explore the evolution of ion channels during the evolutionary history of cetaceans. To do so, we created a bioinformatic pipeline to annotate the repertoire of ion channels in the genome of the species included in our sampling. Our main results show that cetaceans have, on average, fewer protein-coding genes and a higher percentage of annotated ion channels than non-cetacean mammals. Signals of positive selection were detected in ion channels related to the heart, locomotion, visual and neurological phenotypes. Interestingly, we predict that the NaV1.5 ion channel of most toothed whales (odontocetes) is sensitive to tetrodotoxin, similar to NaV1.7, given the presence of tyrosine instead of cysteine, in a specific position of the ion channel. Finally, the gene turnover rate of the cetacean crown group is more than three times faster than that of non-cetacean mammals.
Assuntos
Cetáceos , Evolução Molecular , Canais Iônicos , Animais , Cetáceos/genética , Cetáceos/fisiologia , Canais Iônicos/genética , Canais Iônicos/metabolismo , Filogenia , Biologia Computacional/métodos , GenomaRESUMO
Studying the evolutionary history of gene families is a challenging and exciting task with a wide range of implications. In addition to exploring fundamental questions about the origin and evolution of genes, disentangling their evolution is also critical to those who do functional/structural studies to allow a deeper and more precise interpretation of their results in an evolutionary context. The sirtuin gene family is a group of genes that are involved in a variety of biological functions mostly related to aging. Their duplicative history is an open question, as well as the definition of the repertoire of sirtuin genes among vertebrates. Our results show a well-resolved phylogeny that represents an improvement in our understanding of the duplicative history of the sirtuin gene family. We identified a new sirtuin gene family member (SIRT3.2) that was apparently lost in the last common ancestor of amniotes but retained in all other groups of jawed vertebrates. According to our experimental analyses, elephant shark SIRT3.2 protein is located in mitochondria, the overexpression of which leads to an increase in cellular levels of ATP. Moreover, in vitro analysis demonstrated that it has deacetylase activity being modulated in a similar way to mammalian SIRT3. Our results indicate that there are at least eight sirtuin paralogs among vertebrates and that all of them can be traced back to the last common ancestor of the group that existed between 676 and 615 millions of years ago.
Assuntos
Sirtuína 3 , Sirtuínas , Animais , Sirtuínas/genética , Sirtuína 3/genética , Evolução Molecular , Vertebrados/genética , Filogenia , MamíferosRESUMO
Transient receptor potential (TRP) proteins are a large family of cation-selective channels, surpassed in variety only by voltage-gated potassium channels. Detailed molecular mechanisms governing how membrane voltage, ligand binding, or temperature can induce conformational changes promoting the open state in TRP channels are still a matter of debate. Aiming to unveil distinctive structural features common to the transmembrane domains within the TRP family, we performed phylogenetic reconstruction, sequence statistics, and structural analysis over a large set of TRP channel genes. Here, we report an exceptionally conserved set of residues. This fingerprint is composed of twelve residues localized at equivalent three-dimensional positions in TRP channels from the different subtypes. Moreover, these amino acids are arranged in three groups, connected by a set of aromatics located at the core of the transmembrane structure. We hypothesize that differences in the connectivity between these different groups of residues harbor the apparent differences in coupling strategies used by TRP subgroups.
Assuntos
Canais de Potencial de Receptor Transitório , Filogenia , Domínios Proteicos , Canais de Potencial de Receptor Transitório/química , Canais de Potencial de Receptor Transitório/genéticaRESUMO
The TAR DNA Binding Protein (TARDBP) gene has become relevant after the discovery of its several pathogenic mutations. The lack of evolutionary history is in contrast to the amount of studies found in the literature. This study investigated the evolutionary dynamics associated with the retrotransposition of the TARDBP gene in primates. We identified novel retropseudogenes that likely originated in the ancestors of anthropoids, catarrhines, and lemuriformes, i.e. the strepsirrhine clade that inhabit Madagascar. We also found species-specific retropseudogenes in the Philippine tarsier, Bolivian squirrel monkey, capuchin monkey and vervet. The identification of a retropseudocopy of the TARDBP gene overlapping a lncRNA that is potentially expressed opens a new avenue to investigate TARDBP gene regulation, especially in the context of TARDBP associated pathologies.
Assuntos
Primatas , Tarsiidae , Animais , Cebus , Cercopithecidae , Proteínas de Ligação a DNA/genética , Primatas/genética , Especificidade da Espécie , Tarsiidae/genéticaRESUMO
Golgi phosphoprotein 3 (GOLPH3) was the first reported oncoprotein of the Golgi apparatus. It was identified as an evolutionarily conserved protein upon its discovery about 20 years ago, but its function remains puzzling in normal and cancer cells. The GOLPH3 gene is part of a group of genes that also includes the GOLPH3L gene. Because cancer has deep roots in multicellular evolution, studying the evolution of the GOLPH3 gene family in non-model species represents an opportunity to identify new model systems that could help better understand the biology behind this group of genes. The main goal of this study is to explore the evolution of the GOLPH3 gene family in birds as a starting point to understand the evolutionary history of this oncoprotein. We identified a repertoire of three GOLPH3 genes in birds. We found duplicated copies of the GOLPH3 gene in all main groups of birds other than paleognaths, and a single copy of the GOLPH3L gene. We suggest there were at least three independent origins for GOLPH3 duplicates. Amino acid divergence estimates show that most of the variation is located in the N-terminal region of the protein. Our transcript abundance estimations show that one paralog is highly and ubiquitously expressed, and the others were variable. Our results are an example of the significance of understanding the evolution of the GOLPH3 gene family, especially for unraveling its structural and functional attributes.
Assuntos
Aves/genética , Evolução Molecular , Complexo de Golgi/genética , Proteínas de Membrana/genética , Proteínas Oncogênicas/genética , Sequência de Aminoácidos/genética , Animais , Carcinogênese/genética , Duplicação Gênica , Humanos , Neoplasias/genética , Fosfoproteínas/genética , Alinhamento de SequênciaRESUMO
Essential for calcium homeostasis, TRPV5 and TRPV6 are calcium-selective channels belonging to the transient receptor potential (TRP) gene family. In this study, we investigated the evolutionary history of these channels to add an evolutionary context to the already available physiological information. Phylogenetic analyses revealed that paralogs found in mammals, sauropsids, amphibians, and chondrichthyes, are the product of independent duplication events in the ancestor of each group. Within amniotes, we identified a traceable signature of three amino acids located at the amino-terminal intracellular region. The signature correlates with both the duplication events and the phenotype of fast inactivation observed in mammalian TRPV6 channels. Electrophysiological recordings and mutagenesis revealed that the signature sequence modulates the phenotype of fast inactivation in all clades of vertebrates but reptiles. A transcriptome analysis showed a change in tissue expression from gills, in marine vertebrates, to kidneys in terrestrial vertebrates. Our results highlight a cytoplasmatic structural triad composed by the Helix-Loop-Helix domain, the S2-S3 linker, and the TRP domain helix that is important on modulating the activity of calcium-selective TRPV channels.
Assuntos
Cálcio/metabolismo , Evolução Molecular , Canais de Cátion TRPV/metabolismo , Sequência de Aminoácidos , Anfíbios/metabolismo , Animais , Aves/metabolismo , Brânquias/metabolismo , Células HEK293 , Sequências Hélice-Alça-Hélice , Humanos , Rim/metabolismo , Mamíferos/metabolismo , Mutagênese Sítio-Dirigida , Filogenia , Alinhamento de Sequência , Canais de Cátion TRPV/química , Canais de Cátion TRPV/classificação , Canais de Cátion TRPV/genéticaRESUMO
Nodal is a signaling molecule that belongs to the transforming growth factor-ß superfamily that plays key roles during the early stages of development of animals. In vertebrates Nodal forms an heterodimer with a GDF1/3 protein to activate the Nodal pathway. Vertebrates have a paralog of nodal in their genomes labeled Nodal-related, but the evolutionary history of these genes is a matter of debate, mainly because of the presence of a variable numbers of genes in the vertebrate genomes sequenced so far. Thus, the goal of this study was to investigate the evolutionary history of the Nodal and Nodal-related genes with an emphasis in tracking changes in the number of genes among vertebrates. Our results show the presence of two gene lineages (Nodal and Nodal-related) that can be traced back to the ancestor of jawed vertebrates. These lineages have undergone processes of differential retention and lineage-specific expansions. Our results imply that Nodal and Nodal-related duplicated at the latest in the ancestor of gnathostomes, and they still retain a significant level of functional redundancy. By comparing the evolution of the Nodal/Nodal-related with GDF1/3 gene family, it is possible to infer that there are several types of heterodimers that can trigger the Nodal pathway among vertebrates.
Assuntos
Evolução Molecular , Proteína Nodal/genética , Proteína Nodal/metabolismo , Transdução de Sinais/fisiologia , Vertebrados/genética , Vertebrados/fisiologia , Animais , Biologia Computacional , Regulação da Expressão Gênica , FilogeniaRESUMO
Growth differentiation factors 1 (GDF1) and 3 (GDF3) are members of the transforming growth factor superfamily (TGF-ß) that is involved in fundamental early-developmental processes that are conserved across vertebrates. The evolutionary history of these genes is still under debate due to ambiguous definitions of homologous relationships among vertebrates. Thus, the goal of this study was to unravel the evolution of the GDF1 and GDF3 genes of vertebrates, emphasizing the understanding of homologous relationships and their evolutionary origin. Our results revealed that the GDF1 and GDF3 genes found in anurans and mammals are the products of independent duplication events of an ancestral gene in the ancestor of each of these lineages. The main implication of this result is that the GDF1 and GDF3 genes of anurans and mammals are not 1:1 orthologs. In other words, genes that participate in fundamental processes during early development have been reinvented two independent times during the evolutionary history of tetrapods.
Assuntos
Proteínas de Anfíbios/genética , Fator 1 de Diferenciação de Crescimento/genética , Fator 3 de Diferenciação de Crescimento/genética , Filogenia , Animais , Anuros , MamíferosRESUMO
Dopamine receptors are integral membrane proteins whose endogenous ligand is dopamine. They play a fundamental role in the central nervous system and dysfunction of dopaminergic neurotransmission is responsible for the generation of a variety of neuropsychiatric disorders. From an evolutionary standpoint, phylogenetic relationships among the DRD1 class of dopamine receptors are still a matter of debate as in the literature different tree topologies have been proposed. In contrast, phylogenetic relationships among the DRD 2 group of receptors are well understood. Understanding the time of origin of the different dopamine receptors is also an issue that needs further study, especially for the genes that have restricted phyletic distributions (e.g., DRD2l and DRD4rs). Thus, the goal of this study was to investigate the evolution of dopamine receptors, with emphasis on shedding light on the phylogenetic relationships among the D1 class of dopamine receptors and the time of origin of the DRD2l and DRD4rs gene lineages. Our results recovered the monophyly of the two groups of dopamine receptors. Within the DRD1 group the monophyly of each paralog was recovered with strong support, and phylogenetic relationships among them were well resolved. Within the DRD1 class of dopamine receptors we recovered the sister group relationship between the DRD1C and DRD1E, and this clade was recovered sister to a cyclostome sequence. The DRD1 clade was recovered sister to the aforementioned clade, and the group containing DRD5 receptors was sister to all other DRD1 paralogs. In agreement with the literature, among the DRD2 class of receptors, DRD2 was recovered sister to DRD3, whereas DRD4 was sister to the DRD2/DRD3 clade. According to our phylogenetic tree, the DRD2l and DRD4rs gene lineages would have originated in the ancestor of gnathostomes between 615 and 473 mya. Conservation of sequences required for dopaminergic neurotransmission and small changes in regulatory regions suggest a functional refinement of the dopaminergic pathways along evolution.
RESUMO
Evolutionary studies of genes that have been functionally characterized and whose variation has been associated with pathological conditions represent an opportunity to understand the genetic basis of pathologies. α2-Adrenoreceptors (ADRA2) are a class of G protein-coupled receptors that regulate several physiological processes including blood pressure, platelet aggregation, insulin secretion, lipolysis, and neurotransmitter release. This gene family has been extensively studied from a molecular/physiological perspective, yet much less is known about its evolutionary history. Accordingly, the goal of this study was to investigate the evolutionary history of α2-adrenoreceptors (ADRA2) in vertebrates. Our results show that in addition to the three well-recognized α2-adrenoreceptor genes (ADRA2A, ADRA2B and ADRA2C), we recovered a clade that corresponds to the fourth member of the α2-adrenoreceptor gene family (ADRA2D). We also recovered a clade that possesses two ADRA2 sequences found in two lamprey species. Furthermore, our results show that mammals and crocodiles are characterized by possessing three α2-adrenoreceptor genes, whereas all other vertebrate groups possess the full repertoire of α2-adrenoreceptor genes. Among vertebrates ADRA2D seems to be a dispensable gene, as it was lost two independent times during the evolutionary history of the group. Additionally, we found that most examined species possess the most common alleles described for humans; however, there are cases in which non-human mammals possess the alternative variant. Finally, transcript abundance profiles revealed that during the early evolutionary history of gnathostomes, the expression of ADRA2D in different taxonomic groups became specialized to different tissues, but in the ancestor of sarcopterygians this specialization would have been lost.