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The adult mammalian brain retains some capacity to replenish neurons and glia, holding promise for brain regeneration. Thus, understanding the mechanisms controlling adult neural stem cell (NSC) differentiation is crucial. Paradoxically, adult NSCs in the subependymal zone transcribe genes associated with both multipotency maintenance and neural differentiation, but the mechanism that prevents conflicts in fate decisions due to these opposing transcriptional programmes is unknown. Here we describe intron detention as such control mechanism. In NSCs, while multiple mRNAs from stemness genes are spliced and exported to the cytoplasm, transcripts from differentiation genes remain unspliced and detained in the nucleus, and the opposite is true under neural differentiation conditions. We also show that m6A methylation is the mechanism that releases intron detention and triggers nuclear export, enabling rapid and synchronized responses. m6A RNA methylation operates as an on/off switch for transcripts with antagonistic functions, tightly controlling the timing of NSCs commitment to differentiation.

Eph receptor (Eph) and ephrin signaling regulate fundamental developmental processes through both forward and reverse signaling triggered upon cell–cell contact. In vertebrates, they are both classified into classes A and B, and some representatives have been identified in many metazoan groups, where their expression and functions have been well studied. We have extended previous phylogenetic analyses and examined the presence of Eph and ephrins in the tree of life to determine their origin and evolution. We have found that 1) premetazoan choanoflagellates may already have rudimental Eph/ephrin signaling as they have an Eph-/ephrin-like pair and homologs of downstream-signaling genes; 2) both forward- and reverse-downstream signaling might already occur in Porifera since sponges have most genes involved in these types of signaling; 3) the nonvertebrate metazoan Eph is a type-B receptor that can bind ephrins regardless of their membrane-anchoring structure, glycosylphosphatidylinositol, or transmembrane; 4) Eph/ephrin cross-class binding is specific to Gnathostomata; and 5) kinase-dead Eph receptors can be traced back to Gnathostomata. We conclude that Eph/ephrin signaling is of older origin than previously believed. We also examined the presence of protein domains associated with functional characteristics and the appearance and conservation of downstream-signaling pathways to understand the original and derived functions of Ephs and ephrins. We find that the evolutionary history of these gene families points to an ancestral function in cell–cell interactions that could contribute to the emergence of multicellularity and, in particular, to the required segregation of cell populations.

The DNA Damage Response (DDR) signalling network is an essential system that protects the genome’s integrity. The DDRprot database presented here is a resource that integrates manually curated information on the human DDR network and its sub-pathways. For each particular DDR protein, we present detailed information about its function. If involved in post-translational modifications (PTMs) with each other, we depict the position of the modified residue/s in the three-dimensional structures, when resolved structures are available for the proteins. All this information is linked to the original publication from where it was obtained. Phylogenetic information is also shown, including time of emergence and conservation across 47 selected species, family trees and sequence alignments of homologues. The DDRprot database can be queried by different criteria: pathways, species, evolutionary age or involvement in (PTM). Sequence searches using hidden Markov models can be also used.

The genomic features of Azoarcus sp. CIB reflect its most distinguishing phenotypes as a diazotroph, facultative anaerobe, capable of degrading either aerobically and/or anaerobically a wide range of aromatic compounds, including some toxic hydrocarbons such as toluene and m-xylene, as well as its endophytic lifestyle. The analyses of its genome have expanded the catabolic potential of strain CIB towards common natural compounds, such as certain diterpenes, that were not anticipated as carbon sources. The high number of predicted solvent efflux pumps and heavy metal resistance gene clusters has provided the first evidence for two environmentally-relevant features of this bacterium that remained unknown. Genome mining has revealed several gene clusters likely involved in the endophytic lifestyle of strain CIB, opening the door to the molecular characterization of some plant growth promoting traits. Horizontal gene transfer and mobile genetic elements appear to have played a major role as a mechanism of adaptation of this bacterium to different lifestyles. This work paves the way for a systems biology-based understanding of the abilities of Azoarcus sp. CIB to integrate aerobic and anaerobic metabolism of aromatic compounds, tolerate stress conditions, and interact with plants as an endophyte of great potential for phytostimulation and phytoremediation strategies. Comparative genomics provides an Azoarcus pan genome that confirms the global metabolic flexibility of this genus, and suggests that its phylogeny should be revisited.

The DNA damage response (DDR) is a crucial signaling network that preserves the integrity of the genome. This network is an ensemble of distinct but often overlapping subnetworks, where different components fulfill distinct functions in precise spatial and temporal scenarios. To understand how these elements have been assembled together in humans, we performed comparative genomic analyses in 47 selected species to trace back their emergence using systematic phylogenetic analyses and estimated gene ages. The emergence of the contribution of posttranslational modifications to the complex regulation of DDR was also investigated. This is the first time a systematic analysis has focused on the evolution of DDR subnetworks as a whole. Our results indicate that a DDR core, mostly constructed around metabolic activities, appeared soon after the emergence of eukaryotes, and that additional regulatory capacities appeared later through complex evolutionary process. Potential key posttranslational modifications were also in place then, with interacting pairs preferentially appearing at the same evolutionary time, although modifications often led to the subsequent acquisition of new targets afterwards. We also found extensive gene loss in essential modules of the regulatory network in fungi, plants, and arthropods, important for their validation as model organisms for DDR studies.

[Introducción] Las células están continuamente en riesgo de sufrir daño en el ADN, ya sea desde fuentes exógenas (radiación ionizante, rayos ultravioletas, agentes químicos, etc) o endógenas (errores en la replicación del ADN, especies reactivas de oxígeno, etc) (1,2). Para detectar las lesiones en el ADN, señalizar su presencia y promover la reparación del daño, las células han desarrollado una sofisticada e intrincada red the pathways que conjuntamente constituyen la respuesta al daño en el ADN (DDR). Dependiendo de la naturaleza de la lesión en el ADN (3), del tipo de célula, de la fase del ciclo celular en la que tiene lugar el daño (4), y de si el ADN puede repararse (5), distintos sistemas de reparación del ADN pueden entrar en acción para reparar el ADN dañado. Estos sistemas han sido muy estudiados (6-9), y los principales se pueden clasificar en Reparación de un malapareamiento (Mismatch Repair (MMR)), Reparación de excisión de bases (Base Excision Repair (BER)), Reparación por escisión de nucleótidos (Nucleotide Excision Repair (NER)), Recombinación homóloga (Homologous Recombination (HR)) y Recombinación no homóloga (Non-Homologous End-Joining (NHEJ)). La existencia de estas rutas permite evitar o minimizar posibles alteraciones de las estructuras genómicas que podrían llevar a la pérdida de control proliferativo o a la muerte celular, por lo que asegura la transmisión fidedigna de la información genética a la siguiente generación. La DDR tiene mucho interés por su implicación en cáncer (10-12) y enfermedades tales como Ataxia-telangiectasia (13), Síndrome de Seckel (14), Síndrome de Nijmegen (15), etc. Además, las alteraciones en esta red generan inestabilidad genómica que amenaza la viabilidad de la célula. Esto ha hecho que se estudie enormemente en humanos (16-18), donde varios componentes de la DDR se han estudiado en detalle (19-21). Las rutas de DDR contienen cuatro componentes principales: sensores, mediadores, transductores de la señal, y efector, Aunque se han aislado muchos componentes de DDR en los puntos de rotura del ADN, se conoce muy poco sobre las interacciones precisas que tienen lugar entre los distintos componentes, lo que ha generado la publicación de muchos estudios, algunos contradictorios. Estudios recientes han aumentado el número de componentes relacionados con la DDR, aunque todavía se desconocen en gran medida los procesos funcionales ya que los estudios se realizan principalmente en líneas celulares bajo condiciones experimentales. Por otro lado, aunque todos los organismos deberían tener un sistema de detección del daño para contrarrestar los efectos deletéreos de la inestabilidad genómica, hay poca información disponible. Debido a las grandes diferencias en la biología de las distintas especies, es esperable encontrar enormes diferencias en el ensamblaje de la suma de rutas que componen la DDR. Sin embargo, hay algo en común entre todas las especies, y es que para que un organismo pueda sobrevivir, sus células han de replicarse fidedignamente. De hecho, cada vez que una célula se replica, hay cierto daño causado por el estrés replicativo. Por eso, debe haber un sistema de detección y reparación de daño universal para evitar la inestabilidad genómica., [Objetivo] Nuestro objetivo es delinear el repertorio de proteinas implicadas en DDR a lo largo de la evolución y determinar qué procesos han intervenido en el ensamblaje de estas rutas., [Métodos] La respuesta al daño en el ADN (DDR) es una red de señalización esencial que mantiene la integridad genética. Esta red es un conjunto de sub-redes distintas, pero a menudo solapantes, donde los componentes que participan desempeñan diversas funciones según marcos espacio-temporales precisos. Para comprender cómo estas sub-redes han surgido a lo largo de la evolución y cómo se han ido ensamblando, hemos buscado componentes de DDR en 47 especies que cubren el árbol de la vida. Para ello hemos identificado secuencias ortólogas con InParanoid (24), hemos construido perfiles filogenéticos de las proteínas y hemos agrupado los resultados para identificar distintos grupos de proteínas que han aparecido a lo largo de la evolución. También hemos analizado la composición de dominios de las secuencias de DDR y se han detectado homólogos remotos. Asimismo, hemos analizado las propiedades evolutivas y funcionales de las proteínas de DDR según distintas edades de genes y siguiendo varias clasificaciones. Finalmente, hemos mapeado los resultados en la ruta canónica de DDR en humanos, y hemos hecho comparaciones entre los distintos organismos., [Resultados] Esta es la primera vez que un análisis sistemático cubre la evolución global de la red de DDR. Nuestros resultados indican que la mayoría de los componentes de la DDR son genes antiguos, que todas las sub-redes contienen al menos un representante trazable hasta procariotas, y que el núcleo ancestral de la maquinaria de DDR está principalmente relacionado con reparación, y se construyó sobre actividades de detección y efectores. Modificaciones post-transduccionales tales como fosforilaciones, acetylaciones, sumoylaciones y ubiquitinaciones ya estaban presentes en los eucariotas antiguos., [Conclusión] A lo largo de la evolución, la ampliación de la red ha ocurrido a través de la adición de nuevos componentes que han evolucionado para interaccionar y funcionar junto a los antiguos, lo que puede haber incrementado la complejidad de la red de DDR en términos de precisión y de comunicación con otras redes.

The regulation of signal transduction by phosphorylation and ubiquitination is essential to ensure the correct behavior of eukaryotic cells. We searched for protein families involved in such signaling in several eukaryotic species and in a limited set of prokaryotes, where two members of the Planctomycetes phylum were included as they exhibit eukaryote-like features (Gemmata obscuriglobus and Pirellula staleyi). We identified sequences homologous to eukaryotic serine/threonine kinases (STKs) and E2-ubiquitin conjugating enzymes in the two Planctomycetes species. To extend these analyses to the Planctomycetes/Verrucomicrobia/Chlamydia super-phylum, we performed comparative analyses using domains from kinases, phosphatases and GTPases that serve as signaling signatures, and we analyzed their distributions. We found substantial differences in kinome densities with regards to other prokaryote clades and among the groups in the Planctomycetes/Verrucomicrobia/Chlamydia super-phylum. In addition, we identified the presence of classic eukaryotic E2-conjugating ubiquitin proteins in prokaryotes, these having previously believed to exist only in eukaryotes. Our phylogenetic analyses of the STKs signature domains and E2-enzymes suggest the existence of horizontal gene transfer.

Acidiphilium sp. strain PM (DSM 24941) was isolated from Rio Tinto's acidic, heavy metal-rich waters. Voltammetry experiments revealed that this strain is capable of electricity production even under aerobic conditions. Here we report the draft genome sequence of Acidiphilium sp. PM and a preliminary genome analysis that reveals a versatile respiratory metabolism.

Acidiphilium sp. strain PM (DSM 24941) was isolated from Rio Tinto's acidic, heavy metal-rich waters. Voltammetry experiments revealed that this strain is capable of electricity production even under aerobic conditions. Here we report the draft genome sequence of Acidiphilium sp. PM and a preliminary genome analysis that reveals a versatile respiratory metabolism.

[Background]: Extreme acidic environments are characterized by their high metal content and lack of nutrients (oligotrophy). Macroscopic biofilms and filaments usually grow on the water-air interface or under the stream attached to solid substrates (streamers). In the Río Tinto (Spain), brown filaments develop under the water stream where the Gram-negative iron-oxidizing bacteria Leptospirillum spp. (L. ferrooxidans and L. ferriphilum) and Acidithiobacillus ferrooxidans are abundant. These microorganisms play a critical role in bioleaching processes for industrial (biominery) and environmental applications (acid mine drainage, bioremediation). The aim of this study was to investigate the physiological differences between the free living (planktonic) and the sessile (biofilm associated) lifestyles of Leptospirillum spp. as part of its natural extremely acidophilic community. [Results]: Total RNA extracted from environmental samples was used to determine the composition of the metabolically active members of the microbial community and then to compare the biofilm and planktonic environmental transcriptomes by hybridizing to a genomic microarray of L. ferrooxidans. Genes up-regulated in the filamentous biofilm are involved in cellular functions related to biofilm formation and maintenance, such as: motility and quorum sensing (mqsR, cheAY, fliA, motAB), synthesis of cell wall structures (lnt, murA, murB), specific proteases (clpX/clpP), stress response chaperons (clpB, clpC, grpE-dnaKJ, groESL), etc. Additionally, genes involved in mixed acid fermentation (poxB, ackA) were up-regulated in the biofilm. This result, together with the presence of small organic acids like acetate and formate (1.36 mM and 0.06 mM respectively) in the acidic (pH 1.8) water stream, suggests that either L. ferrooxidans or other member of the microbial community are producing acetate in the acidophilic biofilm under microaerophilic conditions. [Conclusions]: Our results indicate that the acidop