The Origin of GPCRs: Identification of Mammalian like Rhodopsin, Adhesion, Glutamate and Frizzled GPCRs in Fungi

G protein-coupled receptors (GPCRs) in humans are classified into the five main families named Glutamate, Rhodopsin, Adhesion, Frizzled and Secretin according to the GRAFS classification. Previous results show that these mammalian GRAFS families are well represented in the Metazoan lineages, but they have not been shown to be present in Fungi. Here, we systematically mined 79 fungal genomes and provide the first evidence that four of the five main mammalian families of GPCRs, namely Rhodopsin, Adhesion, Glutamate and Frizzled, are present in Fungi and found 142 novel sequences between them. Significantly, we provide strong evidence that the Rhodopsin family emerged from the cAMP receptor family in an event close to the split of Opisthokonts and not in Placozoa, as earlier assumed. The Rhodopsin family then expanded greatly in Metazoans while the cAMP receptor family is found in 3 invertebrate species and lost in the vertebrates. We estimate that the Adhesion and Frizzled families evolved before the split of Unikonts from a common ancestor of all major eukaryotic lineages. Also, the study highlights that the fungal Adhesion receptors do not have N-terminal domains whereas the fungal Glutamate receptors have a broad repertoire of mammalian-like N-terminal domains. Further, mining of the close unicellular relatives of the Metazoan lineage, Salpingoeca rosetta and Capsaspora owczarzaki, obtained a rich group of both the Adhesion and Glutamate families, which in particular provided insight to the early emergence of the N-terminal domains of the Adhesion family. We identified 619 Fungi specific GPCRs across 79 genomes and revealed that Blastocladiomycota and Chytridiomycota phylum have Metazoan-like GPCRs rather than the GPCRs specific for Fungi. Overall, this study provides the first evidence of the presence of four of the five main GRAFS families in Fungi and clarifies the early evolutionary history of the GPCR superfamily

Experiencias de aprendizaje

Libro de experiencias de aprendizaje del grupo de investigación Giteca y de los semilleros de investigación en la que se visualizan las diferentes experiencias lideradas por instructores y aprendices en las diferentes áreas y líneas de formación.Book of learning experiences of the Giteca research group and the research hotbeds in which the different experiences led by instructors and apprentices in the different areas and lines of training are visualized.Propagación in vitro como un camino de aprendizaje para la formación profesional integral -- Experiencias significativas de aprendizaje, laboratorio de hematología y parasitología animal del Complejo Tecnológico para la Gestión Agroempresarial CTPGA-SENA -- Experiencias significativas adquiridas por aprendices en el área de SENNOVA, Complejo Tecnológico para la Gestión Agroempresarial. Regional – Antioquia -- El papel de la prensa escrita en el desarrollo de la competencia textual -- Aprendiendo a Emprender con un emprendedor -- Ven y te cuento sobre ADSI -- Observaciones fenológicas del cultivo de cacao (Theobroma cacao) en los municipios de Tarazá, El Bagre y Caucasia dentro de la formación del programa SENA emprende rural -- Tejiendo sueños desde la formación -- Forraje verde hidropónico como alternativa para disminuir la expansión de la frontera agrícola en el Putumayo -- La importancia del saber hacer para ser competente en el sector agrícola -- Experiencia significativa de aprendizaje semilleros de investigación -- La investigación como ente transformador de pensamientos -- Piscícola Paraguay; Mi Sueño, Mi Proyecto de Vida! -- Estrategia de aprendizaje a través de la investigación y la empresa aplicando un programa de Responsabilidad Social Empresarial –RSE -- Matemática aplicada para procesos agroindustriales de panificaciónna85 página

Whole-exome sequencing of congenital glaucoma patients reveals hypermorphic variants in GPATCH3, a new gene involved in ocular and craniofacial development

Congenital glaucoma (CG) is a heterogeneous, inherited and severe optical neuropathy that originates from maldevelopment of the anterior segment of the eye. To identify new disease genes, we performed whole-exome sequencing of 26 unrelated CG patients. In one patient we identified two rare, recessive and hypermorphic coding variants in GPATCH3, a gene of unidentified function, and 5% of a second group of 170 unrelated CG patients carried rare variants in this gene. The recombinant GPATCH3 protein activated in vitro the proximal promoter of CXCR4, a gene involved in embryo neural crest cell migration. The GPATCH3 protein was detected in human tissues relevant to glaucoma (e.g., ciliary body). This gene was expressed in the dermis, skeletal muscles, periocular mesenchymal-like cells and corneal endothelium of early zebrafish embryos. Morpholino-mediated knockdown and transient overexpression of gpatch3 led to varying degrees of goniodysgenesis and ocular and craniofacial abnormalities, recapitulating some of the features of zebrafish embryos deficient in the glaucoma-related genes pitx2 and foxc1. In conclusion, our data suggest the existence of high genetic heterogeneity in CG and provide evidence for the role of GPATCH3 in this disease. We also show that GPATCH3 is a new gene involved in ocular and craniofacial development.This study has been supported by research grants from the “Instituto de Salud Carlos III/FEDER” (RD12/0034/0003, PI11/00662, PI15/01193 to JE and CP12/03256 to MC), the Ministry of Economy and Competitiveness/FEDER (MINECO, SAF2013-46943-R to MC and PT13/0001/0044 to MG), Mutua Madrileña Foundation (to MC), and the Regional Ministry of Science and Technology of the Board of the Communities of “Castilla-La Mancha” (PEII-2014-002-P to JE). Jesús-José Ferre-Fernández is the recipient of a predoctoral fellowship from the “Instituto de Salud Carlos III” (FI12/00287). Miguel Coca-Prados is “Catedrático Rafael del Pino en Oftalmología” in the “Fundación de Investigación Oftalmológica, Instituto Oftalmológico Fernández-Vega” Oviedo, Spain. Marta Corton is sponsored by the Miguel Servet Program (CP12/03256) from Instituto de Salud Carlos III/FEDER)

The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans

Choanoflagellates are the closest known relatives of metazoans. To discover potential molecular mechanisms underlying the evolution of metazoan multicellularity, we sequenced and analysed the genome of the unicellular choanoflagellate Monosiga brevicollis. The genome contains approximately 9,200 intron- rich genes, including a number that encode cell adhesion and signalling protein domains that are otherwise restricted to metazoans. Here we show that the physical linkages among protein domains often differ between M. brevicollis and metazoans, suggesting that abundant domain shuffling followed the separation of the choanoflagellate and metazoan lineages. The completion of the M. brevicollis genome allows us to reconstruct with increasing resolution the genomic changes that accompanied the origin of metazoans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62649/1/nature06617.pd