National Institute for Bioinformatics

Barcelona, Spain

National Institute for Bioinformatics

Barcelona, Spain
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Gallego A.,University Pompeu Fabra | Mele M.,Center for Genomic Regulation | Mele M.,Harvard University | Mele M.,The Broad Institute of MIT and Harvard | And 16 more authors.
PLoS ONE | Year: 2016

microRNAs are crucial post-transcriptional regulators of gene expression involved in a wide range of biological processes. Although microRNAs are highly conserved among species, the functional implications of existing lineage-specific changes and their role in determining differences between humans and other great apes have not been specifically addressed. We analyzed the recent evolutionary history of 1,595 human microRNAs by looking at their intra- and inter-species variation in great apes using high-coverage sequenced genomes of 82 individuals including gorillas, orangutans, bonobos, chimpanzees and humans. We explored the strength of purifying selection among microRNA regions and found that the seed and mature regions are under similar and stronger constraint than the precursor region. We further constructed a comprehensive catalogue of microRNA species-specific nucleotide substitutions among great apes and, for the first time, investigated the biological relevance that human-specific changes in microRNAs may have had in great ape evolution. Expression and functional analyses of four microRNAs (miR-299-3p, miR-503-3p, miR- 508-3p and miR-541-3p) revealed that lineage-specific nucleotide substitutions and changes in the length of these microRNAs alter their expression as well as the repertoires of target genes and regulatory networks. We suggest that the studied molecular changes could have modified crucial microRNA functions shaping phenotypes that, ultimately, became human-specific. Our work provides a frame to study the impact that regulatory changes may have in the recent evolution of our species. © 2016 Gallego et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Hartasanchez D.A.,University Pompeu Fabra | Braso-Vives M.,University Pompeu Fabra | Fuentes-Diaz J.,University Pompeu Fabra | Valles-Codina O.,University Pompeu Fabra | And 4 more authors.
Bioinformatics | Year: 2015

Summary: SeDuS is the first flexible and user-friendly forward-in-time simulator of patterns of molecular evolution within segmental duplications undergoing interlocus gene conversion and crossover. SeDuS introduces known features of interlocus gene conversion such as biased directionality and dependence on local sequence identity. Additionally, it includes aspects such as different selective pressures acting upon copy number and flexible crossover distributions. A graphical user interface allows fast fine-tuning of relevant parameters and straightforward real-time analysis of the evolution of duplicates. Availability and implementation: SeDuS is implemented in C++ and can be run via command line or through a graphical user interface developed using Qt C++. Source code and binary executables for Linux, OS X and Windows are freely available at A tutorial with a detailed description of implementation, parameters and output files is available online. © 2015 The Author 2015. Published by Oxford University Press. All rights reserved.

Gutierrez J.,CSIC - Institute of Natural Resources and Agriculture Biology of Salamanca | Gonzalez-Perez S.,CSIC - Institute of Natural Resources and Agriculture Biology of Salamanca | Garcia-Garcia F.,National Institute for Bioinformatics | Lorenzo O.,Centro Hispano Luso Of Investigaciones Agrarias | Arellano J.B.,CSIC - Institute of Natural Resources and Agriculture Biology of Salamanca
Plant Signaling and Behavior | Year: 2011

Can Arabidopsis cell suspension cultures (ACSC) provide a useful working model to investigate genetically-controlled defense responses with signaling cascades starting in chloroplasts? In order to provide a convincing answer, we analyzed the early transcriptional profile of Arabidopsis cells at high light (HL). The results showed that ACSC respond to HL in a manner that resembles the singlet oxygen ( 1O 2)-mediated defense responses described for the conditional fluorescent (flu) mutant of Arabidopsis thaliana. The flu mutant is characterized by the accumulation of free protochlorophyllide (Pchlide) in plastids when put into darkness and the subsequent production of 1O 2 when the light is on. In ACSC, 1O 2 is produced in chloroplasts at HL when excess excitation energy flows into photosystem II (PSII). Other reactive oxygen species are also produced in ACSC at HL, but to a lesser extent. When the HL stress ceases, ACSC recovers the initial rate of oxygen evolution and cell growth continues. We can conclude that chloroplasts of ACSC are both photosynthetically active and capable of initiating 1O 2-mediated signaling cascades that activate a broad range of genetically-controlled defense responses. The upregulation of transcripts associated with the biosynthesis and signaling pathways of OPDA (12-oxophytodienoic acid) and ethylene (ET) suggests that the activated defense responses at HL are governed by these two hormones. In contrast to the flu mutant, the 1O 2-mediated defense responses were independent of the upregulation of EDS1 (enhanced disease susceptibility) required for the accumulation of salicylic acid (SA) and genetically-controlled cell death. Interestingly, a high correlation in transcriptional expression was also observed between ACSC at HL, and the aba1 and max4 mutants of Arabidopsis, characterized by defects in the biosynthesis pathways of abscisic acid (ABA) and strigolactones, respectively. © 2011 Landes Bioscience.

Gonzalez-Perez S.,CSIC - Institute of Natural Resources and Agriculture Biology of Salamanca | Gutierrez J.,CSIC - Institute of Natural Resources and Agriculture Biology of Salamanca | Garcia-Garcia F.,National Institute for Bioinformatics | Osuna D.,University of Salamanca | And 4 more authors.
Plant Physiology | Year: 2011

The early transcriptional defense responses and reactive oxygen species (ROS) production in Arabidopsis (Arabidopsis thaliana) cell suspension culture (ACSC), containing functional chloroplasts, were examined at high light (HL). The transcriptional analysis revealed that most of the ROS markers identified among the 449 transcripts with significant differential expression were transcripts specifically up-regulated by singlet oxygen 1O2. On the contrary, minimal correlation was established with transcripts specifically up-regulated by superoxide radical or hydrogen peroxide. The transcriptional analysis was supported by fluorescence microscopy experiments. The incubation of ACSC with the 1O2 sensor green reagent and 2',7'-dichlorofluorescein diacetate showed that the 30-min-HL-treated cultures emitted fluorescence that corresponded with the production of 1O2 but not of hydrogen peroxide. Furthermore, the in vivo photodamage of the D1 protein of photosystem II indicated that the photogeneration of 1O2 took place within the photosystem II reaction center. Functional enrichment analyses identified transcripts that are key components of the ROS signaling transduction pathway in plants as well as others encoding transcription factors that regulate both ROS scavenging and water deficit stress. A meta-analysis examining the transcriptional profiles of mutants and hormone treatments in Arabidopsis showed a high correlation between ACSC at HL and the fluorescent mutant family of Arabidopsis, a producer of 1O2 in plastids. Intriguingly, a high correlation was also observed with ABA deficient1 and more axillary growth4, two mutants with defects in the biosynthesis pathways of two key (apo)carotenoid-derived plant hormones (i.e. abscisic acid and strigolactones, respectively). ACSC has proven to be a valuable system for studying early transcriptional responses to HL stress. © 2011 American Society of Plant Biologists.

Vivas Y.,Rey Juan Carlos University | Martinez-Garcia C.,Rey Juan Carlos University | Izquierdo A.,Rey Juan Carlos University | Garcia-Garcia F.,National Institute for Bioinformatics | And 8 more authors.
BMC Medical Genomics | Year: 2011

Background: The progression towards type 2 diabetes depends on the allostatic response of pancreatic beta cells to synthesise and secrete enough insulin to compensate for insulin resistance. The endocrine pancreas is a plastic tissue able to expand or regress in response to the requirements imposed by physiological and pathophysiological states associated to insulin resistance such as pregnancy, obesity or ageing, but the mechanisms mediating beta cell mass expansion in these scenarios are not well defined. We have recently shown that ob/ob mice with genetic ablation of PPAR2, a mouse model known as the POKO mouse failed to expand its beta cell mass. This phenotype contrasted with the appropriate expansion of the beta cell mass observed in their obese littermate ob/ob mice. Thus, comparison of these models islets particularly at early ages could provide some new insights on early PPAR dependent transcriptional responses involved in the process of beta cell mass expansion. Results: Here we have investigated PPAR dependent transcriptional responses occurring during the early stages of beta cell adaptation to insulin resistance in wild type, ob/ob, PPAR2 KO and POKO mice. We have identified genes known to regulate both the rate of proliferation and the survival signals of beta cells. Moreover we have also identified new pathways induced in ob/ob islets that remained unchanged in POKO islets, suggesting an important role for PPAR in maintenance/activation of mechanisms essential for the continued function of the beta cell. Conclusions: Our data suggest that the expansion of beta cell mass observed in ob/ob islets is associated with the activation of an immune response that fails to occur in POKO islets. We have also indentified other PPAR dependent differentially regulated pathways including cholesterol biosynthesis, apoptosis through TGF- signaling and decreased oxidative phosphorylation. © 2011 Vivas et al.

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