en News - BIOINFORMATICS BARCELONA News Thu, 04 May 2017 12:45:59 +0000 Thu, 04 May 2017 12:45:59 +0000 Houdini 2 (http://houdini.antaviana.cat/) http://www.bioinformaticsbarcelona.eu/news Computational research details the activation mechanism of a protein involved in many diseases
  • p38α is a protein involved in chronic inflammatory diseases and cancer, among other pathological conditions.
  • Published in the journal eLife, the study provides a deeper understanding of the structure of this protein, thereby paving the way for the development of more effective inhibitors.
  • These findings are the result of combining fundamental biological data using computational techniques.

The protein p38α is a member of a family of molecules that transmit outside signals throughout the cell, thus allowing for an appropriate cell response, such as proliferation, differentiation, senescence, or death. Moreover, the participation of p38α in pathological conditions, like chronic inflammatory diseases and cancer, makes it a promising pharmacological target. In this regard, a complete picture of the activation mechanism of this protein is essential in order to design specific inhibitors that do not affect other processes.

The journal eLife has published a study on p38α by Antonija Kuzmanic, an EU Marie Curie COFUND fellow who is undertaking postdoctoral training simultaneously in two IRB Barcelona labs - the Molecular Modelling and Bioinformatics Laboratory and the Signalling and Cell Cycle Laboratory. Collaborative research between the lab headed by Modesto Orozco and that led by Angel R. Nebreda, the latter an international authority on p38α, has provided an integrative picture of the p38α activation mechanism and new insights into the molecular effects of various molecules that regulate the enzymatic activity of the protein.

Using computational techniques, researchers have deciphered the key elements of the complex molecular mechanism underlying p38α activity. This study describes the protein activation mechanism in unprecedented detail and reconciles the apparent contradictory results reported in previous structural studies. "Considering the importance of p38α for pathological processes, we hope the knowledge obtained in this study will help to target the protein with more specificity," stresses Antonija Kuzmanic, first author of the study.

Identifying new inhibitors

p38α has already been targeted for inflammatory diseases and some types of cancer; however, none of the drugs have yet made it to the market. "Our study reveals novel conformations of the protein, which could be used as a starting point in virtual screening studies aimed at uncovering new inhibitors," explains Kuzmanic. And she adds, "We were also able to highlight important electrostatic interactions, which may allow us to explore alternative activation pathways with increased specificity".

A computational biology approach

"We used only computational techniques. Mainly, we employed numerous molecular dynamics simulations combined with an advanced sampling technique called metadynamics," explains Kuzmanic. This combination has an advantage over standard molecular dynamics simulations, as it allows researchers to observe large conformational changes in a reasonable amount of computational time. She goes on to say, "we are able to add statistical significance to the conformations we observed in our simulations".

This study has received funding from the Seventh Framework Programme, the Engineering and Physical Sciences Research Council, the European Research Council, Horizon 2020, and the MINECO (Spanish Ministry of Economy, Industry and Competitiveness). 

 

Reference article:

Antonija Kuzmanic, Ludovico Sutto, Giorgio Saladino, Angel R. Nebreda, Francesco L. Gervasio and Modesto Orozco. Changes in the free-energy landscape of p38α MAP kinase through its canonical activation and binding events as studied by enhanced molecular dynamics simulations. eLife (2017) DOI: 10.7554/eLife.22175

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Thu, 04 May 2017 12:45:59 +0000 http://www.bioinformaticsbarcelona.eu/news//news/59/computational-research-details-the-activation-mechanism-of-a-protein-involved-in-many-diseases http://www.bioinformaticsbarcelona.eu/news/59 0
Made of Genes brings personal genomics to national-scale through its participation in Dubai Future Accelerators Made of Genes, a personal genomics start-up based in Barcelona (Spain) whose beginnings lie in ESADE Business School (both BIB members), has been selected to join the 2nd edition of the Dubai Future Accelerators program, an initiative of the Dubai Future Foundation.

This unique program connects the world's most innovative companies with the government of Dubai to create breakthrough solutions to global challenges. The Dubai Future Accelerators program partners with ground-breaking companies from around the world and gives them the opportunity to find and test new solutions to real-life challenges using the city of Dubai as a living test bed.

The first program, which ended in December 2016, resulted in US $33M in commercial partnerships, MoU's and pilot projects in just three months. Three members of Made of Genes will join the regional carrier Etisalat Digital to work to improve the chronic disease management of UAE patients.

More information at the oficial press release URL.

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Tue, 04 Apr 2017 10:53:28 +0000 http://www.bioinformaticsbarcelona.eu/news//news/57/made-of-genes-brings-personal-genomics-to-national-scale-through-its-participation-in-dubai-future-accelerators http://www.bioinformaticsbarcelona.eu/news/57 0
Alfonso Valencia is appointed as Director of the Life Sciences Department within BSC

The Biologist Alfonso Valencia has been appointed at the Barcelona Supercomputing Center - Centro Nacional de Supercomputación (BSC-CNS) as Director of the Life Sciences Department, with the support of the ICREA program.

Alfonso Valencia is Director of the National Institute of Bioinformatics (Salud Carlos III Institute platform (INB-ISCIII) and node of ELIXIR the European Infrastructure of Bioinformatics), Founder and President of the International Society for Computational Biology and Co-Executive Director of the main journal in the field (Bioinformatics of Oxford University Press).

The incorporation of Valencia to BSC, which participates in the Bioinformatics Barcelona (BIB) Association, confirms the centre's commitment to personalized medicine as an area of future development for supercomputing. In the opinion of the new head of the Life Sciences Department, "the BSC offers a privileged environment to create an analysis platform of genomes of biomedical interest, capable of coordinating the efforts of internal and external BSC groups, making it competitive at an international level. Facing the enormous biomedical challenges of the future will only be possible with the coordination of the incredible scientific and technical resources of the BSC, in the rich scientific environment of Barcelona, and in combination with both National (INB-ISCIII) and European scientific infrastructures (ELIXIR)".

Alfonso Valencia's research is centred in the area of Bioinformatics and Computational Biology. The computational methods for the genome analysis are particularly application to Precision Medicine. He has also worked in the development of computational methods for the prediction of protein structures and functions, the analysis biological networks and for modelling of molecular systems. These methods are based in the development of open and collaborative structures and are immersed in large international collaborative projects.

Alfonso Valencia is also a Member of the Scientific Advisory Committee of the Swiss Institute of Bioinformatics, EBI chemical and protein domain databases, IRB, UPF_DCEX, Greek ELIXIR-Node, amongst others; Associate Editor of eLIFE, PeerJ, FEBS Letters, and co-leader of the new journal f1000 "Bioinformatics, Biomedical Informatics & Computational Biology". In addition to being a member of the European Molecular Biology Organisation (EMBO) and Founder of the BioCreative challenge in text mining.

During the last ten years, Valencia has performed his research in the National Oncology Research Center, CNIO, where he was also the Vice-Director of Basic Research and Director of the Structural Biology and BioComputing Program.

 

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Fri, 17 Mar 2017 11:07:03 +0000 http://www.bioinformaticsbarcelona.eu/news//news/55/alfonso-valencia-is-appointed-as-director-of-the-life-sciences-department-within-bsc http://www.bioinformaticsbarcelona.eu/news/55 0
Genetic signature of natural selection in first Americans

When 18,000 years ago humans entered America through the Bering Strait they found a totally different climate and food. A recent study published in the journal Proceedings of the National Academy of Sciences USA (PNAS) shows that this migration left traces in the genome of Native Americans, descendants of those early settlers. These are genetic variants that facilitate the digestion of fats, which is distinctive feature of adaptation to Arctic climate and diets rich in proteins.

David Comas, a scientist at the Institute of Evolutionary Biology of Barcelona (IBE, CSIC-UPF) and director of the Department of Experimental and Health Sciences at the Pompeu Fabra University (UPF), who has participated in the research, states: "The environmental and dietary pressures that found the first settlers of America marked them genetically."

In fact, this is what in evolutionary biology is known as the founder effect. Namely, from the small group of people who crossed the Strait for the first time, only those who had these mutations survived. "As a result, all the populations that emerged from those early settlers carry the same genetic variants," explains Comas.

The paradox is that Inuit who live in the Arctic Circle still benefit from this biological adaptation, but the Amazonian Indians, who live in a tropical climate, also conserve them. According to Comas, "the fact that current populations contain adaptations of the past is not necessarily negative but can lead to metabolic dysfunctions."

These mutations had already been seen in the Inuit, but now have also been found with high frequencies in many of the 53 current and prehistoric populations that have been studied, including Amazonian tribes and native peoples of North America. Being present in almost all, the scientists believe that the adaptation happened in an ancestral population, before crossing the Strait, and then it was selected due to the environmental conditions.

Understanding how natural selection has shaped our current physiology in response to changes in climate, diet and past diseases allows us to understand the current genetic makeup of humans in relation to the susceptibility of different diseases.

Reference Article: Amorim, C.E.;  Nunes, K.; Meyer, D.; Comas, D.; Bortolini, M.C.; Salzano, F.M.; Hünemeier, T. 2107. Genetic signature of natural selection in first Americans. Proc Natl Acad Sci U S A. pii: 201620541. doi: 10.1073/pnas.1620541114.

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Wed, 08 Mar 2017 11:52:12 +0000 http://www.bioinformaticsbarcelona.eu/news//news/53/genetic-signature-of-natural-selection-in-first-americans http://www.bioinformaticsbarcelona.eu/news/53 0
New role of cholesterol in regulating brain proteins discovered

A study led by researchers of GRIB (IMIM-UPF) and the Institute of Medical Physics and Biophysics at the Faculty of Medicine in Charité Hospital, Berlin, published in the journal Nature Communications, demonstrates that the cholesterol present in cell membranes can interfere with the function of an important brain membrane protein, through a previously unknown mode of interaction. Specifically, cholesterol is capable of regulating the activity of the adenosine receptor, by invading it and accessing the active site. This will allow new ways of interacting with these proteins to be devised that in the future could lead to drugs for treating diseases like Alzheimer's.

The adenosine receptor belongs to the GPCR family (G Protein-Coupled Receptors), a large group of proteins located in cell membranes, which are key in the transmission of signals and communication between cells. GPCRs are therefore involved in the majority of important physiological processes, including the interpretation of sensory stimuli such as vision, smell, and taste, the regulation of the immune and inflammatory system, and behaviour modulation.

Explanatory video in which you can see how cholesterol leaves the neuronal membrane and get within the adenosine receptor:

"Cholesterol is an essential component of neuronal membranes, where GPCRs reside along with other proteins. Interestingly, the levels of cholesterol in the membrane are altered in diseases such as Alzheimer's, where GPCRs like the adenosine receptor play a key role", explains Jana Selent, head of the GPCR Drug Discovery research group of GRIB  (IMIM-UPF). "This study has shown that cholesterol can exert direct action on this important family of proteins in neuronal membranes, the GPCRs, and establishes the basis for a hitherto unknown interaction pathway between the cell membrane and proteins", adds the researcher.

Up to now, it was thought that membrane cholesterol could regulate the activity of these proteins through two mechanisms: either by altering the physical properties of the membrane, or by binding to the surface of the protein. In both cases, it was thought that cholesterol could only exercise its modulatory action from outside the protein.

However, by using latest-generation molecular simulations the researchers were able to detect the fact that cholesterol can leave the neuronal membrane and get within the adenosine receptor, in particular accessing the receptor's active site. With this information, and in collaboration with Dr. Mairena Martin and Dr. José L. Albasanz from the University of Castilla-La Mancha, we designed an experimental protocol using cell assays to demonstrate that cholesterol is able to modulate the activity of this receptor by accessing its interior.

"Cholesterol levels in cell membranes could have a more direct effect than previously thought on the behaviour of key proteins in central nervous system diseases. In particular, high levels of membrane cholesterol like those present in Alzheimer's patients probably block the adenosine receptor, which could in turn be related to certain symptoms observed in this disease", explains Ramón Guixà González, a postdoctoral researcher at the Institute of Medical Physics and Biophysics at the Faculty of Medicine in Charité Hospital in Berlin and first author of the article. "Although other studies are needed to prove this relationship, this work provides key knowledge that could be used in the future in the development of new molecules that, like cholesterol, have the ability to get inside the receptor and modulate its activity", says the researcher.

The results from this study represent a paradigm shift in the relationship between membrane cholesterol and GPCRs in the central nervous system, and open up new avenues of research in fields where the cholesterol-GPCR relationship is essential. It also appears that the cholesterol access pathway into the receptor is an evolutionary footprint. It is therefore necessary to discover whether the molecular mechanism described in this paper is present in other GPCRs and therefore potentially involved in a wide range of central nervous system diseases.

About the GRIB

The Research Programme on Biomedical Informatics (GRIB) is a joint research programme of the Hospital del Mar Medical Research Institute (IMIM) and the Department of Experimental and Health Sciences of the Universitat Pompeu Fabra both of them partners of the Bioinformatics Barcelona Association.

Reference article

Guixà-González R, Albasanz JL, Rodríguez-Epigares I, Pastor M, Sanz F, Martí-Solano M, Manna M, Martínez-Seara H, Hildebrand PW, Martí M, Selent J. Membrane cholesterol access into a G-protein-coupled receptor. NatureCommunications, 8: 14505, 2017. DOI: 10.1038/ncomms14505.

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Mon, 27 Feb 2017 13:25:45 +0000 http://www.bioinformaticsbarcelona.eu/news//news/51/new-role-of-cholesterol-in-regulating-brain-proteins-discovered http://www.bioinformaticsbarcelona.eu/news/51 0
A new study reveals the level of physical activity and sport per European country

Sweden, Finland and Denmark are the European countries that do more sport on a regular basis, according to a study published in the Open Access Library Journal, by the experts Antonio Monleón-Getino, Marta Cubedo, Martín Ríos, from the Faculty of Biology of the University of Barcelona, and Daniel Ríos, professor at the Sales Upper Secondary School in Viladecans (Barcelona). According to the conclusions, people in Portugal, Italy, Spain and especially Greece, are listed below the European average regarding the indicators on population and sport.

Sedentarism and lack of physical activity is having more and more incidences in the public health of western countries. According to the World Health Organization (WHO) , which has been reminding about the value of physical activity to promote health and prevent some pathologies, the lack of physical activity is the fourth risk factor in global mortality, and the main cause of more than 21% breast and colon cancers, the 27% of diabetes cases and around the 30% of the coronary heart diseases.

The new study published in Open Access Library covers general aspects of the physical activity and does not focus on any sport in particular. It is based on the multivariate analysis of data from around 27.000 people from 27 European countries according to the information published by the Eurobarometer of the European Commission on the practice of sport stated by people over 15. For each analysed country, the experts analyse the practice of physical exercise and sport of their inhabitants, who are listed in four categories: the ones who never play sport, barely play, occasionally play, and regularly play sport.



Physical activity in Europe: a new inequality map?

"Once we analysed the regularity with which people do sport in 27 countries of the European Union, we saw that Nordic countries, Sweden, Finland and Denmark, play sport more regularly" says Daniel Ríos, lecturer of secondary education at the Sales High School.

After Sweden, Finland and Denmark, the countries with best indicators of physical activity are Slovenia, the Netherlands, Belgium, Luxembourg, Germany, the United Kingdom and France. The lower levels in physical activity were recorded in Bulgaria and Greece.

"As a conclusion -says Daniel Ríos- we think educational and economical levels of these countries are highly related to the practice of physical activity and sport of the people". This scientific study describes how the regular practice of sport and exercise is related to adults involved in educational activities, and with a high level of satisfaction with their economic status and career profile.

In the case of Spain, "the level of sport practice is co-related with the socioeconomic status, as it was seen in the Survey of Sporting Habits in Spain 2015. The survey, carried out in the National Statistics Plan 2013-2016 by the Ministry of Education, Culture and Sport; the Senior Council for Sports and the National Institute of Statistics, aimed to bring the main indicators of sporting habits and practices of people from all the country" says Antonio Monleón-Getino, from the Department of Genetics, Microbiology and Statistics of the University of Barcelona, and member of the Research Group on Biostatistics and Bioinformatics (GRBIO), team integrated in the platform Bioinformatics Barcelona (BIB).

A multivariate statistical technique with great analytical power

The study uses a multidimensional scaling method (MDS) to represent the series of variables or the 27 European studied countries and a country with an average value (which would be the average of the countries that make the European Union up).

According to professor Daniel Ríos, "the MDS method tries to show in a Euclidean space, with few dimensions, the proximities or distances between a set of objects, countries in this case. This technique combines a great capacity to reduce data with high a high graphic potential and represent them in a space with few dimensions (two or three)".

"The MDS is very interesting because it complements other multivariate techniques (factor analysis, cluster, etc.) and allows resolving complex multivariate data collections where the relation between variables is defined with statistical proximity or distance. In this article, as a methodological novelty, the Bhattacharyya distance is applied to calculate the distance between countries" said the authors.

According to the experts, the new study wants to promote future researches based on the application of multivariate methods on the management and interpretation of statistical information.


Original article

D. Ríos, T. Monleón-Getino, M. Cubedo, M. Ríos. «A Graphical Classification of European Countries According to Physical Activity Level of Its Citizens». Open Access Library Journal, December, 2016.

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Thu, 16 Feb 2017 14:08:04 +0000 http://www.bioinformaticsbarcelona.eu/news//news/49/a-new-study-reveals-the-level-of-physical-activity-and-sport-per-european-country http://www.bioinformaticsbarcelona.eu/news/49 0
CompBioMed, a centre of excellence in computational biomedicine, is born

Predictive models of diseases are gaining importance in medicine thanks to their usefulness when customizing treatments. Hence, computational methods based on human biology have become a key factor for the development of customized medicine. This scenario has led to the birth of CompBioMed project, a centre of excellence in biomedical computing that promotes the uptake and exploitation of high performance computing (HPC) in the field of biomedicine. Basic, clinical and industrial researchers will be able to participate as users in the new project, which, for the moment, will work in three different areas: cardiovascular, molecular and neuromusculoskeletal. University College of London is leading the initiative, which promotes interdisciplinary business opportunities by getting its industrial partners to participate, as well as support and facilitate modelling and simulation activities and provide education to a diverse set of communities.

Among the 14 centres participating in the project is the Computational Biophysics research group, led by the ICREA researcher Gianni de Fabritiis, at the Research Programme on Biomedical Informatics (GRIB), a joint programme between Universitat Pompeu Fabra (UPF) and Hospital del Mar Medical Research Institute (IMIM). This group will play a substantial role in work package 2 of CompBioMed: Molecularly-based Medicine Exemplar Research, and also in work package 6: Empowering Biomedical Applications

The Barcelona Supercomputing Center, (BSC-CNS) is another CompBioMed partner. The researcher Mariano Vázquez, team leader of the CASE Department, is the CompBioMed application manager, responsible for coordinating the research work of the Centre of Excellence. CompBioMed will develop parallel software (including Alya, the BSC's multiphysics simulation code) that will be installed in European supercomputing centres (BSC-CNS, SurfSARA in the Netherlands and EPCC in Scotland) for use by biomedical researchers.

CompBioMed is part of one of the new centres of excellence funded by the Horizon 2020 programme and has funding of more than 4.9 million euros. In addition to University College of London and Pompeu Fabra University, the universities of Amsterdam, Edinburgh, Oxford, Geneva and Sheffield, as well as the Barcelona Supercomputing Centre (Spain); the SURFsara organization (Netherlands); consultant CBK Sci Con (United Kingdom); companies LIFETEC Group (Holland), Bull Sas (France), Janssen Pharmaceutica (Belgium), and Acellera (Spain) and Evotec Ag (Germany), will be the project partners.

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Wed, 15 Feb 2017 12:39:34 +0000 http://www.bioinformaticsbarcelona.eu/news//news/47/compbiomed-a-centre-of-excellence-in-computational-biomedicine-is-born http://www.bioinformaticsbarcelona.eu/news/47 0
Connecting Computational Biomechanics and Systems Biology in Frontiers Journal

Frontiers Journal has introduced a new research topic: Advanced HPC-based Computational Modeling in Biomechanics and Systems Biology. This research topic should contribute to bridging the gap between Computational Biomechanics and Systems Biology, with HPC-based Computational Modeling as the link. 

The topic  is co-edited by Mariano Vázquez, Peter V Coveney, Alfons Hoekstra, and Bastien Chopard from CompBioMed. These concepts are in the core of the European Center of Excellence in Computational Biomedicine (CompBioMed).  

BSC encourages researchers to submit their papers. Submission Deadlines: 31 March 2017 for abstracts and 30 September 2017 for manuscripts.

Further information here.

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Wed, 15 Feb 2017 12:28:09 +0000 http://www.bioinformaticsbarcelona.eu/news//news/45/connecting-computational-biomechanics-and-systems-biology-in-frontiers-journal http://www.bioinformaticsbarcelona.eu/news/45 0
How did some plants become carnivorous?

For the English naturalist Charles Darwin, carnivorous plants were one of the most fascinating species due their extraordinary physiological and ecological properties. These plants live in habitats poor in nutrients -mostly on nitrogen and phosphorous- and have compensated this lack with the ability to digest animals such as insects and other arthropods.

After more than 140 years of Darwin's publication of Insectivorous Plants, an international team identified the key genomic changes that allowed some plants to adopt a carnivorous diet, as seen in a study in which Julio Rozas, Pablo Librado and Alejandro Sánchez-Garcia, from the Faculty of Biology and the Biodiversity Research Institute of the University of Barcelona (IRBio) take part.

Adapting and surviving with a carnivorous diet in nutrient-poor soils is an evolutionary process that some evolutionary unrelated species have been going through, repeatedly and independently, from a same set of genes and proteins, according to the study published in the journal Nature Ecology & Evolution, and coordinated by Mitsuyasu Hasebe and Kenji Fukushima (National Institute for Basic Biology, Japan), Shuaicheng Li (City University of Hong Kong, China), and Victor A. Albert (University at Buffalo, United States).



Discovering the genetic mechanisms that make carnivorous diets possible

All plants are photosynthetic organisms, that is, they turn transform the inorganic matter of the environment into organic molecules (glucose). To complete the lack of nutrients of some soils, carnivorous plants can catch and absorb nutrients from a prey, thanks to an exclusively biological mechanism.

The experts have sequenced the genome of the pitcher plant (Cephalotus follicularis), an Australian species that can be identified for its insectivorous leaves -pit-fall traps that catch insects-, very different from the other leaves. The genome of this species -the second carnivorous plant with the complete genome sequenced after Utricularia gibba- is relatively large, and consists of 1,6 Gb, which is almost half of the human genome. The researchers have identified more than 36.000 genes.

According to Professor Julio Rozas, from the Department of Genetics, Microbiology and Statistics, "these plants' ability to feed from animals in poor soils is the result of the action of natural selection, which independently favoured several genetic changes on the same set of genes. With the comparative analysis of differentially expressed genes in these two kinds of leaves, the genetic changes related to plants' carnivorous diet have been identified".

"According to the results, leaves that catch insects have gained new enzymatic functions: basic chitinase, which breaks down chitin (main component of insects' exoskeleton), and purple acid phosphatase which releases phosphate groups from molecules, and it contributes to  the mobilization of the prey's phosphate", says professor Julio Rozas, who leads the Evolutionary Genomics and Bioinformatics research group at the University of Barcelona and the association Bioinformatics Barcelona (BIB).



Carnivorous plants: parallel evolution

Natural selection has acted on specific evolutionary routes so that plants can feed from animals. According to Dr Alejandro Sánchez-Gracia, "In addition to developing a a different strategy to catch animals, natural selection has also often acted recurrently on the same parts of particular pitcher plant genes in order to gain the ability to digest the prey, a phenomenon known as 'parallel evolution'".

The case of these carnivorous plants is a clear example of convergent evolution, probably due the heavy biological restrictions imposed by extreme nutrient-poor ecosystems. Moreover, the fact that this convergence was accompanied by a parallel molecular evolution in digestive enzymes makes this system an interesting example from the perspective of the study of the evolutionary process. "The examples of parallel evolution at a molecular scale are not very common. Therefore they are very interesting to understand the genetic causes of molecular adaptation and their study can help us to determine the relative role of the different evolutionary forces in biological diversification" says Sánchez-Gracia.


The evolutionary journey of plants towards a carnivorous diet

Which molecular strategies have carnivorous plants used as an adaptive evolutionary response? In their adaptation to the carnivorous diet, the generation of new genes is not always necessary: already existing genes in the plant genome have acquired new biological functions, a process known as co-option.

According to the expert Pablo Librado, "in the study, we have stated that genes originally involved in the defence against certain diseases -or the response to biotic and abiotic stress- have acquired new functions (co-option) related to the ability of feeding from animals. This is the case, for instance, of a specific set of proteins that evolved to act as digestive enzymes".

"The results of co-option, regarding both the digestive enzymes and the amino acid changes seen in these enzymes, show that evolution has acted on a limited number of evolutionary routes in the adaptive transition to the carnivorous diet" explains Librado, who is currently working at Center for Geogenetics, from the University of Copenhagen and the Natural History Museum of Denmark. 



BadiRate, a bioinformatics software created at the University of Barcelona

As part of the research, the experts of the UB and IRBio have remarkably contributed to the genomic analysis, integrating the uncertainty that exists on the species' phylogenetic relations to infer which type of genes have preferentially duplicated or lost in the different plant species. This genomic analysis was carried out mainly with BadiRate, a bioinformatics software created by Pablo Librado and Julio Rozas (University of Barcelona) that proved to be essential to discover which kinds of genes, including digestive enzymes, recurrently accompanied the emergence of carnivorous diets in unrelated plant lineages.


Original Article

K. Fukushima, X. Fang, D. Alvarez-Ponce, H. Cai, L. Carretero-Paulet, C. Chen, T. Chang, K. M. Farr, T. Fujita, Y. Hiwatashi, Y. Hoshi,  T. Imai, M. Kasahara, P. Librado, L. Mao, H. Mori, T. Nishiyama, M. Nozawa, G. Pálfalvi, S. T. Pollard, J. Rozas, A. Sánchez-Gracia, D. Sankoff, T. F. Shibata, S. Shigenobu, N. Sumikawa, T. Uzawa, M. Xie, C. Zheng, D. D. Pollock, V. A. Albert, S. Li, M. Hasebe. «The pitcher plant Cephalotus genome reveals genetic changes associated with carnivory». Nature Ecology & Evolution,  February 2017

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Tue, 07 Feb 2017 11:52:25 +0000 http://www.bioinformaticsbarcelona.eu/news//news/43/how-did-some-plants-become-carnivorous http://www.bioinformaticsbarcelona.eu/news/43 0
The fundamental causes of human ageing explained

Natural selection favours fragile and unhealthy old age if it is due to mutations that are beneficial during childhood. As of 40-50 years of age, natural selection is blind because we have already passed on our genes, whether beneficial or not, to our descendants. Knowing the genes and mutations involved in ageing may help to develop new strategies for the treatment of age-related diseases.

A team led by scientists at the Department of Experimental and Health Sciences at Pompeu Fabra University (UPF) and the Institute of Evolutionary Biology (IBE), a joint UPF-CSIC centre, have shown which are the latest genetic causes of human ageing. The results are published this week in the journal Nature Ecology & Evolution.

Ageing has for a long time been a challenge for the public health system and poses evolutionary biologists with a fascinating scientific puzzle. There is no universal theory about the causes, nor is it clear what its overall impact will be on human health. Now, this study has used all the data accumulated over a decade of research on the genetic bases of complex diseases (from Parkinson's to cancer through diabetes) to test different evolutionary theories of senescence.

To date, efforts to understand the evolutionary causes of ageing had been limited to experimental models like the fruit fly, and the findings were often contradictory. But today, the amount of data available concerning the relationship between genotype and phenotype represents an unprecedented opportunity to conduct these tests in humans. This information is available to the scientific community from large international databases such as the European Genome Phenome Archive (EGA): a joint project between the European Bioinformatics Institute (EBI, Cambridge) and the Centre for Genomic Regulation (CRG, Barcelona).

Arcadi Navarro, former ICREA research professor at UPF, has co-led the study that has examined the results of more than 3,000 studies with over 2,500 markers out of a total of 120 diseases. According to Navarro, "the power to determine whether an individual is healthy or any disease will develop during their life has increased greatly as more and more data have been collected".

To start with, scientists have considered whether the markers for each disease have an effect on youth or old age. The distinction is important because if a mutation has harmful effects in old age, our genes will already have passed on to our offspring and natural selection cannot act.  The results of this study show that the frequency and the effect of the mutations that cause diseases in old age are greater than those that cause disease in early age. "We have found an evolutionary threshold at 40-50 years, a biologically significant age because it limits the reproductive period", says Navarro.

The bioinformatic studies carried out by Juan Antonio Rodríguez, first author of the study, have also shown that there are mutations that are beneficial to youth but are harmful later in old age. However, "as they are positive in the reproductive period they will be favoured by natural selection and passed on to the offspring, and so it will be difficult to remove them", explains Rodríguez.

"The physical decline in old age could be the evolutionary price we have to pay to reach the age of having children healthily", says Elena Bosch, co-leader of the study and group leader at the IBE. For example, a drug that we give to a child can have negative effects when it is old. Conversely, it can also happen that a person that is very sickly as a child, if s/he survives, will enjoy excellent health as a senior citizen.

To start with, scientists have considered whether the markers for each disease have an effect on youth or old age. The distinction is important because if a mutation has harmful effects in old age, our genes will already have passed on to our offspring and natural selection cannot act.  The results of this study show that the frequency and the effect of the mutations that cause diseases in old age are greater than those that cause disease in early age. "We have found an evolutionary threshold at 40-50 years, a biologically significant age because it limits the reproductive period", says Navarro.

The bioinformatic studies carried out by Juan Antonio Rodríguez, first author of the study, have also shown that there are mutations that are beneficial to youth but are harmful later in old age. However, "as they are positive in the reproductive period they will be favoured by natural selection and passed on to the offspring, and so it will be difficult to remove them", explains Rodríguez.

"The physical decline in old age could be the evolutionary price we have to pay to reach the age of having children healthily", says Elena Bosch, co-leader of the study and group leader at the IBE. For example, a drug that we give to a child can have negative effects when it is old. Conversely, it can also happen that a person that is very sickly as a child, if s/he survives, will enjoy excellent health as a senior citizen.

 

Reference: Juan Antonio Rodríguez, Urko M. Marigorta, David A. Hughes, Nino Spataro, Elena Bosch,  Arcadi Navarro. Antagonistic pleiotropy and mutation accumulation influence human senescence and disease. Nature Ecology & Evolution, 2017

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Fri, 03 Feb 2017 11:31:06 +0000 http://www.bioinformaticsbarcelona.eu/news//news/41/the-fundamental-causes-of-human-ageing-explained http://www.bioinformaticsbarcelona.eu/news/41 0