82 results on '"Dopazo H"'
Search Results
2. Mitogenomic analysis of extant condor species provides insight into the molecular evolution of vultures
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De Panis, D., Lambertucci, S. A., Wiemeyer, G., Dopazo, H., Almeida, F. C., Mazzoni, C. J., Gut, M., Gut, I., and Padró, J.
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- 2021
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3. Additional file 1 of Transcriptional responses are oriented towards different components of the rearing environment in two Drosophila sibling species
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De Panis, D., Dopazo, H., Bongcam-Rudloff, E., Conesa, A., and Hasson, E.
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Additional file 1. Supporting document: Detailed methods, procedures, and protocols.
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- 2022
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4. Additional file 2 of Transcriptional responses are oriented towards different components of the rearing environment in two Drosophila sibling species
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De Panis, D., Dopazo, H., Bongcam-Rudloff, E., Conesa, A., and Hasson, E.
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Additional file 2. Supporting tables: TableS1-S7.
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- 2022
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5. Additional file 3 of Transcriptional responses are oriented towards different components of the rearing environment in two Drosophila sibling species
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De Panis, D., Dopazo, H., Bongcam-Rudloff, E., Conesa, A., and Hasson, E.
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Additional file 3. Supporting figures: Fig.S1-S10.
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- 2022
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6. Transcriptional responses are oriented towards different components of the rearing environment in two Drosophila sibling species
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De Panis, D., Dopazo, H., Bongcam-Rudloff, Erik, Conesa, A., and Hasson, E.
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Cactaceae ,Evolutionary Biology ,Larva ,Genetics ,Animals ,Drosophila ,Transcriptome ,Zoology ,Adaptation, Physiological ,Biotechnology - Abstract
BackgroundThe chance to compare patterns of differential gene expression in related ecologically distinct species can be particularly fruitful to investigate the genetics of adaptation and phenotypic plasticity. In this regard, a powerful technique such as RNA-Seq applied to ecologically amenable taxa allows to address issues that are not possible in classic model species. Here, we study gene expression profiles and larval performance of the cactophilic siblingsDrosophila buzzatiiandD. koepferaereared in media that approximate natural conditions and evaluate both chemical and nutritional components of the diet. These closely related species are complementary in terms of host-plant use since the primary host of one is the secondary of the other.D. koepferaeis mainly a columnar cactus dweller whileD. buzzatiiprefersOpuntiahosts.ResultsOur comparative study shows thatD. buzzatiiandD. koepferaehave different transcriptional strategies to face the challenges posed by their natural resources. The former has greater transcriptional plasticity, and its response is mainly modulated by alkaloids of its secondary host, while the latter has a more canalized genetic response, and its transcriptional plasticity is associated with the cactus species.ConclusionsOur study unveils a complex pleiotropic genetic landscape in both species, with functional links that relate detox responses and redox mechanisms with developmental and neurobiological processes. These results contribute to deepen our understanding of the role of host plant shifts and natural stress driving ecological specialization.
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- 2021
7. A model for the emergence of adaptive subsystems
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Dopazo, H., Gordon, M. B., Perazzo, R., and Risau-Gusman, S.
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- 2003
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8. A model for the interaction of learning and evolution
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Dopazo, H., Gordon, M. B., Perazzo, R., and Risau-Gusman, S.
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- 2001
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9. Phylemon 2.0: a suite of web-tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing
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Sanchez, R., primary, Serra, F., additional, Tarraga, J., additional, Medina, I., additional, Carbonell, J., additional, Pulido, L., additional, de Maria, A., additional, Capella-Gutierrez, S., additional, Huerta-Cepas, J., additional, Gabaldon, T., additional, Dopazo, J., additional, and Dopazo, H., additional
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- 2011
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10. Phylemon: a suite of web tools for molecular evolution, phylogenetics and phylogenomics
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Tarraga, J., primary, Medina, I., additional, Arbiza, L., additional, Huerta-Cepas, J., additional, Gabaldon, T., additional, Dopazo, J., additional, and Dopazo, H., additional
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- 2007
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11. PupaSuite: finding functional single nucleotide polymorphisms for large-scale genotyping purposes
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Conde, L., primary, Vaquerizas, J. M., additional, Dopazo, H., additional, Arbiza, L., additional, Reumers, J., additional, Rousseau, F., additional, Schymkowitz, J., additional, and Dopazo, J., additional
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- 2006
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12. Phylogenomics and the number of characters required for obtaining an accurate phylogeny of eukaryote model species
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Dopazo, H., primary, Santoyo, J., additional, and Dopazo, J., additional
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- 2004
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13. Mitochondrial DNA variability in viviparous and ovoviviparous populations of the urodele Salamandra salamandra
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Dopazo, H., primary, Boto, L., additional, and Alberch, P., additional
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- 1998
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14. Geographic variation in allozymes of populations of Salamandra salamandra (Amphibia: Urodela) exhibiting distinct reproductive modes
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Alcobendas, M., primary, Dopazo, H., additional, and Alberch, P., additional
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- 1996
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15. Geographic variation in allozymes of populations of Salamandra salamandra(Amphibia: Urodela) exhibiting distinct reproductive modes
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Alcobendas, M., Dopazo, H., and Alberch, P.
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The populations of the urodele Salamandra salamandrain the Northern Iberian Peninsula exhibit very different coloration patterns and a remarkable range in reproductive modes (from giving birth to a large number of aquatic larvae to a parturition event of just a few fully metamorphosed, i.e. terrestrial, offspring). Electrophoretic study of geographic variation in allozymes shows that this extraordinary diversity, particularly in reproductive modes, is not accompanied by a genetic differentiation of similar magnitude. All the populations sampled along a transect crossing the Northern part of the Iberian Peninsula and encompassing the various reproductive strategies, as previously described, can be ascribed to a single species, because of small interpopulational genetic distances (ranging DNeifrom 0.05 to 0.199) and absence of fixed (diagnostic) alleles. A variety of phenetic and cladistic methods were used to elucidate the relationship among populations, based on allozyme data. These methods defined two well corroborated clusters: the first contains populations of salamanders with a blotched dorsal coloration pattern and characterized by parturition of aquatic larvae; the second group is composed of populations exhibiting a striped dorsal coloration pattern, smaller adult body size, and giving birth to fully metamorphosed terrestrial offspring. The latter group also encompasses some populations where mixed parturition events, which include both larvae and metamorphosed offspring, which have been recorded (Dopazo and Alberch, 1994). The absence of a correlation between genetic and geographic distance suggests that the mode of differentiation of the species is based on at least two successive events of isolation, radiation, and secondary contact between populations. Furthermore, the validity of the described “subspecies” is questioned by our data, which point out the need for a detailed systematic study of Salamandrafrom a global perspective. “Viviparity”, here meaning giving birth to fully metamorphosed offspring, originated once and occurs as intraspecific, and even as intrapopulational variation. Thus, we confirm a system where a major evolutionary innovation -the acquisition of independence from the aquatic media in the primitive amphibian complex life cycle-, can be studied at the microevolutionary, i.e., intra- and inter-populational level.
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- 1996
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16. Selective pressure at the codon level improves the prediction of disease related protein mutations in human
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Emidio Capriotti, Arbiza, L., Rita Casadio, Dopazo, J., Dopazo, H., Marti Renom, M. A., ANTHONY BROOKES, STEPHEN CHANOCK, NANCY COX, XAVIER ESTIVILL, PUI-YAN KWOK, STEVE SCHERER, Capriotti E., Arbiza L., Casadio R., Dopazo J., Dopazo H., Marti-Renom M.A., DOPAZO J., VILLA I FREIXA J., GUTIERREZ DE TERAN H., CONESA A., and LENGAUER T, ROST B, SHUSTER P
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HUMAN DISEASES ,SELECTIVE PRESSURE ,SNP - Abstract
Predicting the functional impact of protein variation is one of the most challenging problems in Bioinformatics with direct implications for biomedicine. A rapidly growing number of genome-scale studies provide large amounts of experimental data allowing the application of rigorous statistical approaches for predicting if a given single point mutation has or not an impact on human health. Up until now, existing methods have limited their source data to either protein or gene information. Novel in this work, we take advantage of both and focus on protein evolutionary information by using estimated selective pressures at the codon level. Here we introduce a new method called SeqProfCod (acronym for sequence, profile and codon information) to predict the likeliness that a given protein variant is associated or not with human disease. In this work we also demonstrate that the majority of human mutations that are associated with disease are also under strong purifying selection ((ω
17. Selective pressure at the codon level improves the prediction of disease related protein mutations in human
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Lengauer T, Rost B., Emidio Capriotti, Arbiza, L., Rita Casadio, Dopazo, J., Dopazo, H., and Marti Renom, M. A.
18. Recent human evolution has shaped geographical differences in susceptibility to disease
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Bosch Elena, Faria Rui, Morcillo-Suárez Carlos, Calafell Francesc, Casals Ferran, Lao Oscar, Marigorta Urko M, Serra François, Bertranpetit Jaume, Dopazo Hernán, and Navarro Arcadi
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Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Searching for associations between genetic variants and complex diseases has been a very active area of research for over two decades. More than 51,000 potential associations have been studied and published, a figure that keeps increasing, especially with the recent explosion of array-based Genome-Wide Association Studies. Even if the number of true associations described so far is high, many of the putative risk variants detected so far have failed to be consistently replicated and are widely considered false positives. Here, we focus on the world-wide patterns of replicability of published association studies. Results We report three main findings. First, contrary to previous results, genes associated to complex diseases present lower degrees of genetic differentiation among human populations than average genome-wide levels. Second, also contrary to previous results, the differences in replicability of disease associated-loci between Europeans and East Asians are highly correlated with genetic differentiation between these populations. Finally, highly replicated genes present increased levels of high-frequency derived alleles in European and Asian populations when compared to African populations. Conclusions Our findings highlight the heterogeneous nature of the genetic etiology of complex disease, confirm the importance of the recent evolutionary history of our species in current patterns of disease susceptibility and could cast doubts on the status as false positives of some associations that have failed to replicate across populations.
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- 2011
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19. Identification of conserved domains in the promoter regions of nitric oxide synthase 2: implications for the species-specific transcription and evolutionary differences
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Boscá Lisardo, Dopazo Hernán, Vaquerizas Juan M, and Rico Daniel
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Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background The majority of the genes involved in the inflammatory response are highly conserved in mammals. These genes are not significantly expressed under normal conditions and are mainly regulated at the transcription and prost-transcriptional level. Transcription from the promoters of these genes is very dependent on NF-κB activation, which integrates the response to diverse extracellular stresses. However, in spite of the high conservation of the pattern of promoter regulation in κB-regulated genes, there is inter-species diversity in some genes. One example is nitric oxide synthase 2 (NOS-2), which exhibits a species-specific pattern of expression in response to infection or pro-inflammatory challenge. Results We have conducted a comparative genomic analysis of NOS-2 with different bioinformatic approaches. This analysis shows that in the NOS-2 gene promoter the position and the evolutionary divergence of some conserved regions are different in rodents and non-rodent mammals, and in particular in primates. Two not previously described distal regions in rodents that are similar to the unique upstream region responsible of the NF-κB activation of NOS-2 in humans are fragmented and translocated to different locations in the rodent promoters. The rodent sequences moreover lack the functional κB sites and IFN-γ response sites present in the homologous human, rhesus monkey and chimpanzee regions. The absence of κB binding in these regions was confirmed by electrophoretic mobility shift assays. Conclusion The data presented reveal divergence between rodents and other mammals in the location and functionality of conserved regions of the NOS-2 promoter containing NF-κB and IFN-γ response elements.
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- 2007
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20. From genes to functional classes in the study of biological systems
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Huerta-Cepas Jaime, Dopazo Hernán, Arbiza Leonardo, Al-Shahrour Fátima, Mínguez Pablo, Montaner David, and Dopazo Joaquín
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background With the popularisation of high-throughput techniques, the need for procedures that help in the biological interpretation of results has increased enormously. Recently, new procedures inspired in systems biology criteria have started to be developed. Results Here we present FatiScan, a web-based program which implements a threshold-independent test for the functional interpretation of large-scale experiments that does not depend on the pre-selection of genes based on the multiple application of independent tests to each gene. The test implemented aims to directly test the behaviour of blocks of functionally related genes, instead of focusing on single genes. In addition, the test does not depend on the type of the data used for obtaining significance values, and consequently different types of biologically informative terms (gene ontology, pathways, functional motifs, transcription factor binding sites or regulatory sites from CisRed) can be applied to different classes of genome-scale studies. We exemplify its application in microarray gene expression, evolution and interactomics. Conclusion Methods for gene set enrichment which, in addition, are independent from the original data and experimental design constitute a promising alternative for the functional profiling of genome-scale experiments. A web server that performs the test described and other similar ones can be found at: http://www.babelomics.org.
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- 2007
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21. The Population Genetic Structure of Ctenomys porteousi (Rodentia: Octodontidae)
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Massarini, A., Dopazo, H. J., Bouzat, J. L., and Hasson, E.
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- 1992
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22. Use of estimated evolutionary strength at the codon level improves the prediction of disease-related protein mutations in humans
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Joaquín Dopazo, Rita Casadio, Hernán Dopazo, Marc A. Marti-Renom, Emidio Capriotti, Leonardo Arbiza, Capriotti E., Arbiza L., Casadio R., Dopazo J., Dopazo H., and Marti-Renom M.A.
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Source data ,Iduronic Acid ,DNA Mutational Analysis ,SNP ,Computational biology ,Biology ,Polymorphism, Single Nucleotide ,Genome ,HUMAN DISEASE ,Evolution, Molecular ,Protein sequencing ,Genetic variation ,Genetics ,Humans ,Genetic Predisposition to Disease ,Codon ,Databases, Protein ,Gene ,Genetics (clinical) ,disease ,Genome, Human ,Point mutation ,PROTEIN SEQUENCE ,Computational Biology ,Genetic Variation ,Proteins ,bioinformatics ,POINT MUTATION ,evolutionary strength ,Support vector machine ,nsSNP ,sequence profile ,Human genome ,EVOLUTIONARY STRENGTH ,Tumor Suppressor Protein p53 ,Algorithms - Abstract
Predicting the functional impact of protein variation is one of the most challenging problems in bioinformatics. A rapidly growing number of genome-scale studies provide large amounts of experimental data, allowing the application of rigorous statistical approaches for predicting whether a given single point mutation has an impact on human health. Up until now, existing methods have limited their source data to either protein or gene information. Novel in this work, we take advantage of both and focus on protein evolutionary information by using estimated selective pressures at the codon level. Here we introduce a new method (SeqProfCod) to predict the likelihood that a given protein variant is associated with human disease or not. Our method relies on a support vector machine (SVM) classifier trained using three sources of information: protein sequence, multiple protein sequence alignments, and the estimation of selective pressure at the codon level. SeqProfCod has been benchmarked with a large dataset of 8,987 single point mutations from 1,434 human proteins from SWISS-PROT. It achieves 82% overall accuracy and a correlation coefficient of 0.59, indicating that the estimation of the selective pressure helps in predicting the functional impact of single-point mutations. Moreover, this study demonstrates the synergic effect of combining two sources of information for predicting the functional effects of protein variants: protein sequence/profile-based information and the evolutionary estimation of the selective pressures at the codon level. The results of large-scale application of SeqProfCod over all annotated point mutations in SWISS-PROT (available for download at http://sgu.bioinfo.cipf.es/services/Omidios/; last accessed: 24 August 2007), could be used to support clinical studies.
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- 2008
23. Selective pressures at a codon-level predict deleterious mutations in human disease genes
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Jordi Burguet, Leonardo Arbiza, Serena Duchi, David Montaner, David Pantoja-Uceda, Joaquín Dopazo, Antonio Pineda-Lucena, Hernán Dopazo, Arbiza L, Duchi S, Montaner D, Burguet J, Pantoja-Uceda D, Pineda-Lucena A, Dopazo J, and Dopazo H
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Nonsynonymous substitution ,Models, Molecular ,Molecular Sequence Data ,Single-nucleotide polymorphism ,Biology ,medicine.disease_cause ,Evolution, Molecular ,Negative selection ,Structural Biology ,Neoplasms ,Databases, Genetic ,medicine ,Humans ,codon-based models ,Amino Acid Sequence ,Selection, Genetic ,Codon ,Molecular Biology ,Gene ,Comparative genomics ,Genetics ,Mutation ,Models, Genetic ,Genome, Human ,Genetic Diseases, Inborn ,Proteins ,human disease ,Genes, p53 ,deleterious mutation ,Amino Acid Substitution ,Tumor Suppressor Protein p53 ,comparative genomic ,purifying selection ,Synonymous substitution ,Function (biology) - Abstract
Deleterious mutations affecting biological function of proteins are constantly being rejected by purifying selection from the gene pool. The non-synonymous/synonymous substitution rate ratio (omega) is a measure of selective pressure on amino acid replacement mutations for protein-coding genes. Different methods have been developed in order to predict non-synonymous changes affecting gene function. However, none has considered the estimation of selective constraints acting on protein residues. Here, we have used codon-based maximum likelihood models in order to estimate the selective pressures on the individual amino acid residues of a well-known model protein: p53. We demonstrate that the number of residues under strong purifying selection in p53 is much higher than those that are strictly conserved during the evolution of the species. In agreement with theoretical expectations, residues that have been noted to be of structural relevance, or in direct association with DNA, were among those showing the highest signals of purifying selection. Conversely, those changing according to a neutral, or nearly neutral mode of evolution, were observed to be irrelevant for protein function. Finally, using more than 40 human disease genes, we demonstrate that residues evolving under strong selective pressures (omega
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- 2006
24. Associations Between rs9939609 FTO Polymorphism With Nutrient and Food Intake and Adherence to Dietary Patterns in an Urban Argentinian Population.
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Olmedo L, Luna FJ, Zubrzycki J, Dopazo H, and Pellon-Maison M
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- Humans, Male, Female, Cross-Sectional Studies, Adult, Argentina, Middle Aged, Alleles, Polymorphism, Single Nucleotide, Eating genetics, Body Mass Index, Genotype, Nutrients, Energy Intake, Dietary Patterns, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Urban Population statistics & numerical data, Diet statistics & numerical data, Feeding Behavior
- Abstract
Background: The A allele of rs9939609 polymorphism at the FTO gene has been consistently associated with higher body mass index in different populations, but conflicting results have been found regarding its contribution to food intake variability., Objective: This study aimed to investigate the association between this genetic variant and nutrient and food intake in an urban Argentinian population., Design: A cross-sectional, analytic investigation was performed between October 2018 and February 2020., Participants/settings: Adults of both sexes residing in La Plata, Argentina, were recruited through social networks (Instagram and Facebook). Of 179 eligible adults, a total of 173 adults were included in the final analyses., Outcome Measures: Nutrient and food group intake data were obtained by an interview-administered food frequency questionnaire. Height and weight were measured, and genotypes were obtained by real-time polymerase chain reaction., Statistical Analyses: The per-allele effect on nutrient and food group intake was assessed by general linear models, adjusting for age, sex, educational level, total energy intake, and body mass index. Dietary patterns were derived by principal component analysis. The association of the A allele with adherence to each dietary pattern was also evaluated by the general linear model., Results: The frequency of the risk allele was 27%. A-carriers showed a higher total fat (1.88 [0.55, 3.21] % of total energy intake), saturated fatty acids (0.82 [0.25-1.39] % of total energy intake), and monounsaturated fatty acids (0.66 [0.08, 1.24] % of total energy intake), and a lower carbohydrate (-1.99 [-3.48, -0.50] % of total energy intake) intake than TT homozygous. A-carriers also reported a higher "milk and yogurt" (1.08 [0.24, 1.91] % of total energy intake), "animal fats" (1.09 [0.14-2.03] % of total energy intake), and fat-rich ultraprocessed foods (2.10 [0.52, 3.67] % of total energy intake) intake in comparison with TT homozygous. Furthermore, A-carriers showed higher adherence to the Western dietary pattern., Conclusion: The A allele contributed to nutrient and food intake variability in the studied population and was associated with the consumption of saturated fatty acids-enriched foods., (Copyright © 2024 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)
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- 2024
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25. Assessing the hidden diversity underlying consensus sequences of SARS-CoV-2 using VICOS, a novel bioinformatic pipeline for identification of mixed viral populations.
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Goya S, Sosa E, Nabaes Jodar M, Torres C, König G, Acuña D, Ceballos S, Distéfano AJ, Dopazo H, Dus Santos M, Fass M, Fernández Do Porto D, Fernández A, Gallego F, Gismondi MI, Gramundi I, Lusso S, Martí M, Mazzeo M, Mistchenko AS, Muñoz Hidalgo M, Natale M, Nardi C, Ousset J, Peralta AV, Pintos C, Puebla AF, Pianciola L, Rivarola M, Turjanski A, Valinotto L, Vera PA, Zaiat J, Zubrycki J, Aulicino P, and Viegas M
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- Humans, SARS-CoV-2 genetics, Phylogeny, Genome, Viral, Computational Biology, Consensus Sequence, COVID-19, Coinfection
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Introduction: Coinfection with two SARS-CoV-2 viruses is still a very understudied phenomenon. Although next generation sequencing methods are very sensitive to detect heterogeneous viral populations in a sample, there is no standardized method for their characterization, so their clinical and epidemiological importance is unknown., Material and Methods: We developed VICOS (Viral COinfection Surveillance), a new bioinformatic algorithm for variant calling, filtering and statistical analysis to identify samples suspected of being mixed SARS-CoV-2 populations from a large dataset in the framework of a community genomic surveillance. VICOS was used to detect SARS-CoV-2 coinfections in a dataset of 1,097 complete genomes collected between March 2020 and August 2021 in Argentina., Results: We detected 23 cases (2%) of SARS-CoV-2 coinfections. Detailed study of VICOS's results together with additional phylogenetic analysis revealed 3 cases of coinfections by two viruses of the same lineage, 2 cases by viruses of different genetic lineages, 13 were compatible with both coinfection and intra-host evolution, and 5 cases were likely a product of laboratory contamination., Discussion: Intra-sample viral diversity provides important information to understand the transmission dynamics of SARS-CoV-2. Advanced bioinformatics tools, such as VICOS, are a necessary resource to help unveil the hidden diversity of SARS-CoV-2., Competing Interests: Declaration of Competing Interest The authors declare no competing interest or personal relationship that might have affected the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)
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- 2023
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26. Ortholog genes from cactophilic Drosophila provide insight into human adaptation to hallucinogenic cacti.
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Padró J, De Panis DN, Luisi P, Dopazo H, Szajnman S, Hasson E, and Soto IM
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- Adaptation, Physiological genetics, Animals, Drosophila genetics, Genomics, Hallucinogens, Humans, Alkaloids, Cactaceae chemistry
- Abstract
Cultural transformations of lifestyles and dietary practices have been key drivers of human evolution. However, while most of the evidence of genomic adaptations is related to the hunter-gatherer transition to agricultural societies, little is known on the influence of other major cultural manifestations. Shamanism is considered the oldest religion that predominated throughout most of human prehistory and still prevails in many indigenous populations. Several lines of evidence from ethno-archeological studies have demonstrated the continuity and importance of psychoactive plants in South American cultures. However, despite the well-known importance of secondary metabolites in human health, little is known about its role in the evolution of ethnic differences. Herein, we identified candidate genes of adaptation to hallucinogenic cactus in Native Andean populations with a long history of shamanic practices. We used genome-wide expression data from the cactophilic fly Drosophila buzzatii exposed to a hallucinogenic columnar cactus, also consumed by humans, to identify ortholog genes exhibiting adaptive footprints of alkaloid tolerance. Genomic analyses in human populations revealed a suite of ortholog genes evolving under recent positive selection in indigenous populations of the Central Andes. Our results provide evidence of selection in genetic variants related to alkaloids toxicity, xenobiotic metabolism, and neuronal plasticity in Aymara and Quechua populations, suggesting a possible process of gene-culture coevolution driven by religious practices., (© 2022. The Author(s).)
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- 2022
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27. Evolution of the Insect PPK Gene Family.
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Latorre-Estivalis JM, Almeida FC, Pontes G, Dopazo H, Barrozo RB, and Lorenzo MG
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- Animals, Bees genetics, Genes, Insect, Insecta genetics, Phylogeny, Drosophila melanogaster genetics, Evolution, Molecular
- Abstract
Insect pickpocket (PPK) receptors mediate diverse functions, among them the detection of mechano- and chemo-sensory stimuli. Notwithstanding their relevance, studies on their evolution only focused on Drosophila. We have analyzed the genomes of 26 species of eight orders including holometabolous and hemimetabolous insects (Blattodea, Orthoptera, Hemiptera, Phthiraptera, Hymenoptera, Lepidoptera, Coleoptera, and Diptera), to characterize the evolution of this gene family. PPKs were detected in all genomes analyzed, with 578 genes distributed in seven subfamilies. According to our phylogeny, ppk17 is the most divergent member, composing the new subfamily VII. PPKs evolved under a gene birth-and-death model that generated lineage-specific expansions usually located in clusters, while purifying selection affected several orthogroups. Subfamily V was the largest, including a mosquito-specific expansion that can be considered a new target for pest control. PPKs present a high gene turnover generating considerable variation. On one hand, Musca domestica (59), Aedes albopictus (51), Culex quinquefasciatus (48), and Blattella germanica (41) presented the largest PPK repertoires. On the other hand, Pediculus humanus (only ppk17), bees, and ants (6-9) had the smallest PPK sets. A subset of prevalent PPKs was identified, indicating very conserved functions for these receptors. Finally, at least 20% of the sequences presented calmodulin-binding motifs, suggesting that these PPKs may amplify sensory responses similarly as proposed for Drosophila melanogaster ppk25. Overall, this work characterized the evolutionary history of these receptors revealing relevant unknown gene sequence features and clade-specific expansions., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)
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- 2021
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28. Metagenomic analysis of gut microbiota in non-treated plaque psoriasis patients stratified by disease severity: development of a new Psoriasis-Microbiome Index.
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Dei-Cas I, Giliberto F, Luce L, Dopazo H, and Penas-Steinhardt A
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- Adolescent, Adult, Bacteroides, Bacteroidetes, Biodiversity, Biomarkers metabolism, Clostridiales, Computational Biology, Cross-Sectional Studies, Faecalibacterium, Female, Firmicutes, Genome, Human, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, RNA, Ribosomal, 16S genetics, Young Adult, Gastrointestinal Microbiome, Metagenomics, Psoriasis diagnosis, Psoriasis microbiology
- Abstract
Psoriasis is an immune-mediated skin disorder. Imbalance of gut microbial populations has been implicated in many diseases. We aimed to investigate whether there were differences in gut microbiota in psoriasis patients vs non-psoriasis controls and between psoriasis severity groups. 55 psoriasis patients and 27 controls were included. V3-V4 regions of the 16S rRNA gene of fecal samples were analyzed using Illumina MiSeq. Bioinformatic analysis was performed. We found changes in gut microbiome composition depending on their psoriasis status as determined by weighted unifrac (p < 0.05), in particular an increase in Firmicutes and depletion of Bacteroidetes in psoriasis patients. Additionally, the Faecalibacterium and Blautia genus were higher in psoriasis patients while Bacteroides and Paraprevotella in non-psoriasis controls (p < 0.05, LDA score > 2). Moderate-to-severe psoriasis patients had lower biodiversity than mild psoriatic patients (p = 0.049). No differences for beta-diversity were found. We developed a Psoriasis-Microbiota Index (PMI), which discriminated among psoriasis patients and controls with sensitivity: 0.78 and specificity: 0.79. Furthermore, we performed a meta-analysis with published data to validate this index. We demonstrated gut dysbiosis in psoriasis patients, suggesting a role in psoriasis pathophysiology. Furthermore, we developed a PMI with the potential to discriminate between psoriasis patients and controls across different populations, which could be used as a biomarker in the clinical practice.
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- 2020
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29. Fine-scale genomic analyses of admixed individuals reveal unrecognized genetic ancestry components in Argentina.
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Luisi P, García A, Berros JM, Motti JMB, Demarchi DA, Alfaro E, Aquilano E, Argüelles C, Avena S, Bailliet G, Beltramo J, Bravi CM, Cuello M, Dejean C, Dipierri JE, Jurado Medina LS, Lanata JL, Muzzio M, Parolin ML, Pauro M, Paz Sepúlveda PB, Rodríguez Golpe D, Santos MR, Schwab M, Silvero N, Zubrzycki J, Ramallo V, and Dopazo H
- Subjects
- Argentina, Black People ethnology, Colonialism, DNA genetics, Enslavement, Genetic Markers, Genetic Variation, Genetics, Population, Genotype, Human Migration, Humans, Indians, South American ethnology, Models, Genetic, White People ethnology, Black People genetics, Genome, Human, Indians, South American genetics, Marriage, Pedigree, White People genetics
- Abstract
Similarly to other populations across the Americas, Argentinean populations trace back their genetic ancestry into African, European and Native American ancestors, reflecting a complex demographic history with multiple migration and admixture events in pre- and post-colonial times. However, little is known about the sub-continental origins of these three main ancestries. We present new high-throughput genotyping data for 87 admixed individuals across Argentina. This data was combined to previously published data for admixed individuals in the region and then compared to different reference panels specifically built to perform population structure analyses at a sub-continental level. Concerning the Native American ancestry, we could identify four Native American components segregating in modern Argentinean populations. Three of them are also found in modern South American populations and are specifically represented in Central Andes, Central Chile/Patagonia, and Subtropical and Tropical Forests geographic areas. The fourth component might be specific to the Central Western region of Argentina, and it is not well represented in any genomic data from the literature. As for the European and African ancestries, we confirmed previous results about origins from Southern Europe, Western and Central Western Africa, and we provide evidences for the presence of Northern European and Eastern African ancestries., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: PL provides consulting services to myDNAmap S.L. JMB and JZ are employed by Biocódices S.A. HD is the scientific director of Biocódices S.A. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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- 2020
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30. A Rare Nonsense Mutation in the Glucokinase Regulator Gene Is Associated With a Rapidly Progressive Clinical Form of Nonalcoholic Steatohepatitis.
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Pirola CJ, Flichman D, Dopazo H, Fernández Gianotti T, San Martino J, Rohr C, Garaycoechea M, Gazzi C, Castaño GO, and Sookoian S
- Abstract
We report on the presence of a rare nonsense mutation (rs149847328, p.Arg227Ter) in the glucokinase regulator ( GCKR ) gene in an adult patient with nonalcoholic fatty liver disease (NAFLD), morbid obesity, and type 2 diabetes; this patient developed a progressive histological form of the disease. Analysis of paired (5 years apart) liver biopsies (at baseline and follow-up) showed progression of simple steatosis to severe nonalcoholic steatohepatitis and cirrhosis. Study design involved an initial exploration that consisted of deep sequencing of 14 chromosomal regions in 96 individuals (64 of whom were patients with NAFLD who were diagnosed by liver biopsy that showed the full spectrum of histological severity). We further performed a replication study to explore the presence of rs149847328 that included a sample of 517 unrelated individuals in a case-control study (n = 390), including patients who were morbidly obese (n = 127). Exploration of sequence variation by next-generation sequencing of exons, exon-intron boundaries, and 5' and 3' untranslated regions of 14 genomic loci that encode metabolic enzymes of the tricarboxylic acid cycle revealed the presence of heterozygosity for the p.Arg227Ter mutation, the frequency of which is 0.0003963 (4:10,000; Exome Aggregation Consortium database). GCKR protein expression was markedly decreased in the liver of the affected patient compared with patients with NAFLD who carry the wild-type allele. Sequencing of the same 14 genomic loci in 95 individuals failed to reveal the rare mutation. The rarity of p.Arg227Ter was confirmed in a more extensive screening. Conclusion: While rare variants/mutations are difficult to detect in even reasonably large samples (frequency of the mutant allele of p.Arg227Ter was ~1:1,000 in our data set), the presence of this mutation should be suspected as potentially associated with NAFLD, particularly in young adults at the extreme of histological phenotypes. Hepatology Communications 2018;0:0-0).
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- 2018
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31. Genetic variation in long noncoding RNAs and the risk of nonalcoholic fatty liver disease.
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Sookoian S, Rohr C, Salatino A, Dopazo H, Fernandez Gianotti T, Castaño GO, and Pirola CJ
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- Epigenesis, Genetic, Female, Gene Expression, Genetic Predisposition to Disease, Genetic Variation, Humans, Male, Middle Aged, Non-alcoholic Fatty Liver Disease pathology, Non-alcoholic Fatty Liver Disease genetics, RNA, Long Noncoding genetics
- Abstract
The human transcriptome comprises a myriad of non protein-coding RNA species, including long noncoding RNAs (lncRNAs), which have a remarkable role in transcriptional and epigenetic regulation. We hypothesized that variants in lncRNAs influence the susceptibility to nonalcoholic fatty liver disease (NAFLD). Using next generation sequencing, we performed a survey of genetic variation associated with randomly selected lncRNA-genomic regions located within both experimentally validated and computationally predicted regulatory elements. We used a two-stage (exploratory, n = 96 and replication, n = 390) case-control approach that included well-characterized patients with NAFLD diagnosed by liver biopsy. We sequenced > 263 megabase pairs at quality score > Q17, in a total of 2,027,565 reads, including 170 lncRNA-genomic regions. In the sequencing analysis and the validated dataset, we found that the rs2829145 A/G located in a lncRNA (lnc-JAM2-6) was associated with NAFLD and the disease severity. Prediction of regulatory elements in lnc-JAM2-6 showed potential sequence-specific binding motifs of oncogenes MAFK and JUND, and the transcription factor CEBPB that is involved in inflammatory response. The A-allele was significantly associated with NAFLD as disease trait (p = 0.0081) and the disease severity (NASH-nonalcoholic steatohepatitis vs controls: OR 2.36 [95% CI: 1.54-3.62], p = 0.000078). The A-allele carriers also have significantly higher body mass index and glucose-related traits compared with homozygous GG. Hence, our results suggest that variation in lncRNAs contributes to NAFLD severity, while pointing toward the complexity of the genetic component of NAFLD, which involves still unexplored regulatory regions of the genome.
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- 2017
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32. Mitochondrial genome architecture in non-alcoholic fatty liver disease.
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Sookoian S, Flichman D, Scian R, Rohr C, Dopazo H, Gianotti TF, Martino JS, Castaño GO, and Pirola CJ
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- Adult, Case-Control Studies, DNA, Mitochondrial genetics, Female, Genetic Predisposition to Disease, Germ-Line Mutation, Haplotypes, Humans, Liver Cirrhosis genetics, Male, Middle Aged, Mitochondria, Liver genetics, Mutation, Mutation, Missense genetics, Oxidative Phosphorylation, Polymorphism, Genetic, Severity of Illness Index, Genome, Mitochondrial, Non-alcoholic Fatty Liver Disease genetics
- Abstract
Non-alcoholic fatty liver disease (NAFLD) is associated with mitochondrial dysfunction, a decreased liver mitochondrial DNA (mtDNA) content, and impaired energy metabolism. To understand the clinical implications of mtDNA diversity in the biology of NAFLD, we applied deep-coverage whole sequencing of the liver mitochondrial genomes. We used a multistage study design, including a discovery phase, a phenotype-oriented study to assess the mutational burden in patients with steatohepatitis at different stages of liver fibrosis, and a replication study to validate findings in loci of interest. We also assessed the potential protein-level impact of the observed mutations. To determine whether the observed changes are tissue-specific, we compared the liver and the corresponding peripheral blood entire mitochondrial genomes. The nuclear genes POLG and POLG2 (mitochondrial DNA polymerase-γ) were also sequenced. We observed that the liver mtDNA of patients with NAFLD harbours complex genomes with a significantly higher mutational (1.28-fold) rate and degree of heteroplasmy than in controls. The analysis of liver mitochondrial genomes of patients with different degrees of fibrosis revealed that the disease severity is associated with an overall 1.4-fold increase in mutation rate, including mutations in genes of the oxidative phosphorylation (OXPHOS) chain. Significant differences in gene and protein expression patterns were observed in association with the cumulative number of OXPHOS polymorphic sites. We observed a high degree of homology (∼98%) between the blood and liver mitochondrial genomes. A missense POLG p.Gln1236His variant was associated with liver mtDNA copy number. In conclusion, we have demonstrated that OXPHOS genes contain the highest number of hotspot positions associated with a more severe phenotype. The variability of the mitochondrial genomes probably originates from a common germline source; hence, it may explain a fraction of the 'missing heritability' of NAFLD. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
- Published
- 2016
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33. Transcriptome modulation during host shift is driven by secondary metabolites in desert Drosophila.
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De Panis DN, Padró J, Furió-Tarí P, Tarazona S, Milla Carmona PS, Soto IM, Dopazo H, Conesa A, and Hasson E
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- Adaptation, Physiological, Animals, Argentina, Desert Climate, Larva genetics, Alkaloids chemistry, Cactaceae chemistry, Drosophila genetics, Transcriptome
- Abstract
High-throughput transcriptome studies are breaking new ground to investigate the responses that organisms deploy in alternative environments. Nevertheless, much remains to be understood about the genetic basis of host plant adaptation. Here, we investigate genome-wide expression in the fly Drosophila buzzatii raised in different conditions. This species uses decaying tissues of cactus of the genus Opuntia as primary rearing substrate and secondarily, the necrotic tissues of the columnar cactus Trichocereus terscheckii. The latter constitutes a harmful host, rich in mescaline and other related phenylethylamine alkaloids. We assessed the transcriptomic responses of larvae reared in Opuntia sulphurea and T. terscheckii, with and without the addition of alkaloids extracted from the latter. Whole-genome expression profiles were massively modulated by the rearing environment, mainly by the presence of T. terscheckii alkaloids. Differentially expressed genes were mainly related to detoxification, oxidation-reduction and stress response; however, we also found genes involved in development and neurobiological processes. In conclusion, our study contributes new data onto the role of transcriptional plasticity in response to alternative rearing environments., (© 2016 John Wiley & Sons Ltd.)
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- 2016
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34. Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level.
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Sookoian S, Castaño GO, Scian R, Fernández Gianotti T, Dopazo H, Rohr C, Gaj G, San Martino J, Sevic I, Flichman D, and Pirola CJ
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- Alanine Transaminase blood, Alanine Transaminase genetics, Amino Acids metabolism, Aspartate Aminotransferase, Cytoplasmic blood, Aspartate Aminotransferase, Cytoplasmic genetics, Aspartate Aminotransferase, Mitochondrial blood, Aspartate Aminotransferase, Mitochondrial genetics, Biomarkers blood, Case-Control Studies, Cell Line, Tumor, Citric Acid Cycle, Cohort Studies, Cross-Sectional Studies, Fatty Liver etiology, Female, Humans, Insulin Resistance, Isoenzymes blood, Isoenzymes genetics, Isoenzymes metabolism, Liver pathology, Liver physiopathology, Male, Metabolic Syndrome genetics, Metabolic Syndrome metabolism, Metabolic Syndrome pathology, Metabolic Syndrome physiopathology, Middle Aged, Non-alcoholic Fatty Liver Disease blood, Non-alcoholic Fatty Liver Disease pathology, Non-alcoholic Fatty Liver Disease physiopathology, Polymorphism, Single Nucleotide, Alanine Transaminase metabolism, Aspartate Aminotransferase, Cytoplasmic metabolism, Aspartate Aminotransferase, Mitochondrial metabolism, Enzyme Induction, Gluconeogenesis, Liver metabolism, Non-alcoholic Fatty Liver Disease metabolism
- Abstract
Background: Extensive epidemiologic studies have shown that cardiovascular disease and the metabolic syndrome (MetS) are associated with serum concentrations of liver enzymes; however, fundamental characteristics of this relation are currently unknown., Objective: We aimed to explore the role of liver aminotransferases in nonalcoholic fatty liver disease (NAFLD) and MetS., Design: Liver gene- and protein-expression changes of aminotransferases, including their corresponding isoforms, were evaluated in a case-control study of patients with NAFLD (n = 42), which was proven through a biopsy (control subjects: n = 10). We also carried out a serum targeted metabolite profiling to the glycolysis, gluconeogenesis, and Krebs cycle (n = 48) and an exploration by the next-generation sequencing of aminotransferase genes (n = 96). An in vitro study to provide a biological explanation of changes in the transcriptional level and enzymatic activity of aminotransferases was included., Results: Fatty liver was associated with a deregulated liver expression of aminotransferases, which was unrelated to the disease severity. Metabolite profiling showed that serum aminotransferase concentrations are a signature of liver metabolic perturbations, particularly at the amino acid metabolism and Krebs cycle level. A significant and positive association between systolic hypertension and liver expression levels of glutamic-oxaloacetic transaminase 2 (GOT2) messenger RNA (Spearman R = 0.42, P = 0.03) was observed. The rs6993 located in the 3' untranslated region of the GOT2 locus was significantly associated with features of the MetS, including arterial hypertension [P = 0.028; OR: 2.285 (95% CI: 1.024, 5.09); adjusted by NAFLD severity] and plasma lipid concentrations., Conclusions: In the context of an abnormal hepatic triglyceride accumulation, circulating aminotransferases rise as a consequence of the need for increased reactions of transamination to cope with the liver metabolic derangement that is associated with greater gluconeogenesis and insulin resistance. Hence, to maintain homeostasis, the liver upregulates these enzymes, leading to changes in the amounts of amino acids released into the circulation., (© 2016 American Society for Nutrition.)
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- 2016
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35. Selective constraints on protamine 2 in primates and rodents.
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Lüke L, Tourmente M, Dopazo H, Serra F, and Roldan ER
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- Animals, Biological Evolution, Male, Mating Preference, Animal, Primates, Rodentia, Sperm Head physiology, Spermatozoa physiology, Protamines genetics, Selection, Genetic
- Abstract
Background: Protamines are sperm nuclear proteins with a crucial role in chromatin condensation. Their function is strongly linked to sperm head morphology and male fertility. Protamines appear to be affected by a complex pattern of selective constraints. Previous studies showed that sexual selection affects protamine coding sequence and expression in rodents. Here we analyze selective constraints and post-copulatory sexual selection acting on protamine 2 (Prm2) gene sequences of 53 species of primates and rodents. We focused on possible differences in selective constraints between these two clades and on the two functional domains of PRM2 (cleaved- and mature-PRM2). We also assessed if and how changes in Prm2 coding sequence may affect sperm head dimensions., Results: The domain of Prm2 that is cleaved off during binding to DNA (cleaved-Prm2) was found to be under purifying selection in both clades, whereas the domain that remains bound to DNA (mature-Prm2) was found to be positively selected in primates and under relaxed constraint in rodents. Changes in cleaved-Prm2 coding sequence are significantly correlated to sperm head width and elongation in rodents. Contrary to expectations, a significant effect of sexual selection was not found on either domain or clade., Conclusions: Mature-PRM2 may be free to evolve under less constraint due to the existence of PRM1 as a more conserved and functionally redundant copy. The cleaved-PRM2 domain seems to play an important role in sperm head shaping. However, sexual selection on its sequence may be difficult to detect until it is identified which sperm head phenotype (shape and size) confers advantages for sperm performance in different mammalian clades.
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- 2016
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36. Epigenetic Modifications in the Biology of Nonalcoholic Fatty Liver Disease: The Role of DNA Hydroxymethylation and TET Proteins.
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Pirola CJ, Scian R, Gianotti TF, Dopazo H, Rohr C, Martino JS, Castaño GO, and Sookoian S
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- 5-Methylcytosine analogs & derivatives, Adult, Cytosine metabolism, DNA Methylation genetics, Epigenesis, Genetic, Female, Genetic Predisposition to Disease, Heat-Shock Proteins genetics, Humans, Male, Middle Aged, Mixed Function Oxygenases, Organelle Biogenesis, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Cytosine analogs & derivatives, DNA-Binding Proteins genetics, Liver metabolism, Liver pathology, Mitochondria, Liver metabolism, Non-alcoholic Fatty Liver Disease epidemiology, Non-alcoholic Fatty Liver Disease genetics, Non-alcoholic Fatty Liver Disease metabolism, Proto-Oncogene Proteins genetics, Transcription Factors genetics
- Abstract
The 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification whose role in the pathogenesis of metabolic-related complex diseases remains unexplored; 5-hmC appears to be prevalent in the mitochondrial genome. The Ten-Eleven-Translocation (TET) family of proteins is responsible for catalyzing the conversion of 5-methylcytosine to 5-hmC. We hypothesized that epigenetic editing by 5-hmC might be a novel mechanism through which nonalcoholic fatty liver disease (NAFLD)-associated molecular traits could be explained.Hence, we performed an observational study to explore global levels of 5-hmC in fresh liver samples of patients with NAFLD and controls (n = 90) using an enzyme-linked-immunosorbent serologic assay and immunohistochemistry. We also screened for genetic variation in TET 1-3 loci by next generation sequencing to explore its contribution to the disease biology. The study was conducted in 2 stages (discovery and replication) and included 476 participants.We observed that the amount of 5-hmC in the liver of both NAFLD patients and controls was relatively low (up to 0.1%); a significant association was found with liver mitochondrial DNA copy number (R = 0.50, P = 0.000382) and PPARGC1A-mRNA levels (R = -0.57, P = 0.04).We did not observe any significant difference in the 5-hmC nuclear immunostaining score between NAFLD patients and controls; nevertheless, we found that patients with NAFLD (0.4 ± 0.5) had significantly lower nonnuclear-5-hmC staining compared with controls (1.8 ± 0.8), means ± standard deviation, P = 0.028. The missense p.Ile1123Met variant (TET1-rs3998860) was significantly associated with serum levels of caspase-generated CK-18 fragment-cell death biomarker in the discovery and replication stage, and the disease severity (odds ratio: 1.47, 95% confidence interval: 1.10-1.97; P = 0.005). The p.Ile1762Val substitution (TET2-rs2454206) was associated with liver PPARGC1A-methylation and transcriptional levels, and Type 2 diabetes.Our results suggest that 5-hmC might be involved in the pathogenesis of NAFLD by regulating liver mitochondrial biogenesis and PPARGC1A expression. Genetic diversity at TET loci suggests an "epigenetic" regulation of programmed liver-cell death and a TET-mediated fine-tuning of the liver PPARGC1A-transcriptional program.
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- 2015
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37. Analysis of Five Gene Sets in Chimpanzees Suggests Decoupling between the Action of Selection on Protein-Coding and on Noncoding Elements.
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Santpere G, Carnero-Montoro E, Petit N, Serra F, Hvilsom C, Rambla J, Heredia-Genestar JM, Halligan DL, Dopazo H, Navarro A, and Bosch E
- Subjects
- Actins genetics, Animals, Complement System Proteins genetics, Genes, Humans, Introns, Mutation, Open Reading Frames, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Untranslated Regions, Evolution, Molecular, Pan troglodytes genetics, Selection, Genetic
- Abstract
We set out to investigate potential differences and similarities between the selective forces acting upon the coding and noncoding regions of five different sets of genes defined according to functional and evolutionary criteria: 1) two reference gene sets presenting accelerated and slow rates of protein evolution (the Complement and Actin pathways); 2) a set of genes with evidence of accelerated evolution in at least one of their introns; and 3) two gene sets related to neurological function (Parkinson's and Alzheimer's diseases). To that effect, we combine human-chimpanzee divergence patterns with polymorphism data obtained from target resequencing 20 central chimpanzees, our closest relatives with largest long-term effective population size. By using the distribution of fitness effect-alpha extension of the McDonald-Kreitman test, we reproduce inferences of rates of evolution previously based only on divergence data on both coding and intronic sequences and also obtain inferences for other classes of genomic elements (untranslated regions, promoters, and conserved noncoding sequences). Our results suggest that 1) the distribution of fitness effect-alpha method successfully helps distinguishing different scenarios of accelerated divergence (adaptation or relaxed selective constraints) and 2) the adaptive history of coding and noncoding sequences within the gene sets analyzed is decoupled., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)
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- 2015
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38. Neutral theory predicts the relative abundance and diversity of genetic elements in a broad array of eukaryotic genomes.
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Serra F, Becher V, and Dopazo H
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- Algorithms, Animals, Humans, Likelihood Functions, Stochastic Processes, Chromosomes genetics, Genetic Variation, Genome, Models, Genetic
- Abstract
It is universally true in ecological communities, terrestrial or aquatic, temperate or tropical, that some species are very abundant, others are moderately common, and the majority are rare. Likewise, eukaryotic genomes also contain classes or "species" of genetic elements that vary greatly in abundance: DNA transposons, retrotransposons, satellite sequences, simple repeats and their less abundant functional sequences such as RNA or genes. Are the patterns of relative species abundance and diversity similar among ecological communities and genomes? Previous dynamical models of genomic diversity have focused on the selective forces shaping the abundance and diversity of transposable elements (TEs). However, ideally, models of genome dynamics should consider not only TEs, but also the diversity of all genetic classes or "species" populating eukaryotic genomes. Here, in an analysis of the diversity and abundance of genetic elements in >500 eukaryotic chromosomes, we show that the patterns are consistent with a neutral hypothesis of genome assembly in virtually all chromosomes tested. The distributions of relative abundance of genetic elements are quite precisely predicted by the dynamics of an ecological model for which the principle of functional equivalence is the main assumption. We hypothesize that at large temporal scales an overarching neutral or nearly neutral process governs the evolution of abundance and diversity of genetic elements in eukaryotic genomes.
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- 2013
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39. Positive selection in nucleoporins challenges constraints on early expressed genes in Drosophila development.
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Mensch J, Serra F, Lavagnino NJ, Dopazo H, and Hasson E
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- Animals, Dosage Compensation, Genetic, Drosophila melanogaster embryology, Genes, Insect, Drosophila Proteins genetics, Drosophila melanogaster genetics, Evolution, Molecular, Genes, Developmental, Nuclear Pore Complex Proteins genetics, Selection, Genetic
- Abstract
Developmental conservation among related species is a common generalization known as von Baer's third law and implies that early stages of development are the most refractory to change. The "hourglass model" is an alternative view that proposes that middle stages are the most constrained during development. To investigate this issue, we undertook a genomic approach and provide insights into how natural selection operates on genes expressed during the first 24 h of Drosophila ontogeny in the six species of the melanogaster group for which whole genome sequences are available. Having studied the rate of evolution of more than 2,000 developmental genes, our results showed differential selective pressures at different moments of embryogenesis. In many Drosophila species, early zygotic genes evolved slower than maternal genes indicating that mid-embryogenesis is the stage most refractory to evolutionary change. Interestingly, positively selected genes were found in all embryonic stages even during the period with the highest developmental constraint, emphasizing that positive selection and negative selection are not mutually exclusive as it is often mistakenly considered. Among the fastest evolving genes, we identified a network of nucleoporins (Nups) as part of the maternal transcriptome. Specifically, the acceleration of Nups was driven by positive selection only in the more recently diverged species. Because many Nups are involved in hybrid incompatibilities between species of the Drosophila melanogaster subgroup, our results link rapid evolution of early developmental genes with reproductive isolation. In summary, our study revealed that even within functional groups of genes evolving under strong negative selection many positively selected genes could be recognized. Understanding these exceptions to the broad evolutionary conservation of early expressed developmental genes can shed light into relevant processes driving the evolution of species divergence.
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- 2013
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40. Evolution of the biosynthesis of di-myo-inositol phosphate, a marker of adaptation to hot marine environments.
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Gonçalves LG, Borges N, Serra F, Fernandes PL, Dopazo H, and Santos H
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- Archaea genetics, Archaea physiology, Bacteria genetics, Bacteria metabolism, Biomarkers metabolism, Environment, Gene Transfer, Horizontal, Genome, Nucleotidyltransferases biosynthesis, Nucleotidyltransferases metabolism, Phylogeny, Seawater chemistry, Seawater microbiology, Acclimatization physiology, Archaea metabolism, Hot Temperature, Inositol Phosphates biosynthesis
- Abstract
The synthesis of di-myo-inositol phosphate (DIP), a common compatible solute in hyperthermophiles, involves the consecutive actions of inositol-1-phosphate cytidylyltransferase (IPCT) and di-myo-inositol phosphate phosphate synthase (DIPPS). In most cases, both activities are present in a single gene product, but separate genes are also found in a few organisms. Genes for IPCT and DIPPS were found in the genomes of 33 organisms, all with thermophilic/hyperthermophilic lifestyles. Phylogeny of IPCT/DIPPS revealed an incongruent topology with 16S RNA phylogeny, thus suggesting horizontal gene transfer. The phylogenetic tree of the DIPPS domain was rooted by using phosphatidylinositol phosphate synthase sequences as out-group. The root locates at the separation of genomes with fused and split genes. We propose that the gene encoding DIPPS was recruited from the biosynthesis of phosphatidylinositol. The last DIP-synthesizing ancestor harboured separated genes for IPCT and DIPPS and this architecture was maintained in a crenarchaeal lineage, and transferred by horizontal gene transfer to hyperthermophilic marine Thermotoga species. It is plausible that the driving force for the assembly of those two genes in the early ancestor is related to the acquired advantage of DIP producers to cope with high temperature. This work corroborates the view that Archaea were the first hyperthermophilic organisms., (© 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.)
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- 2012
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41. Evolutionary Genomics of Genes Involved in Olfactory Behavior in the Drosophila melanogaster Species Group.
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Lavagnino N, Serra F, Arbiza L, Dopazo H, and Hasson E
- Abstract
Previous comparative genomic studies of genes involved in olfactory behavior in Drosophila focused only on particular gene families such as odorant receptor and/or odorant binding proteins. However, olfactory behavior has a complex genetic architecture that is orchestrated by many interacting genes. In this paper, we present a comparative genomic study of olfactory behavior in Drosophila including an extended set of genes known to affect olfactory behavior. We took advantage of the recent burst of whole genome sequences and the development of powerful statistical tools to analyze genomic data and test evolutionary and functional hypotheses of olfactory genes in the six species of the Drosophila melanogaster species group for which whole genome sequences are available. Our study reveals widespread purifying selection and limited incidence of positive selection on olfactory genes. We show that the pace of evolution of olfactory genes is mostly independent of the life cycle stage, and of the number of life cycle stages, in which they participate in olfaction. However, we detected a relationship between evolutionary rates and the position that the gene products occupy in the olfactory system, genes occupying central positions tend to be more constrained than peripheral genes. Finally, we demonstrate that specialization to one host does not seem to be associated with bursts of adaptive evolution in olfactory genes in D. sechellia and D. erecta, the two specialists species analyzed, but rather different lineages have idiosyncratic evolutionary histories in which both historical and ecological factors have been involved.
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- 2012
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42. Discovery of an ebolavirus-like filovirus in europe.
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Negredo A, Palacios G, Vázquez-Morón S, González F, Dopazo H, Molero F, Juste J, Quetglas J, Savji N, de la Cruz Martínez M, Herrera JE, Pizarro M, Hutchison SK, Echevarría JE, Lipkin WI, and Tenorio A
- Subjects
- Animals, Base Sequence, DNA, Viral analysis, Disease Outbreaks, Ebolavirus genetics, Genome, Hemorrhagic Fever, Ebola pathology, Hemorrhagic Fever, Ebola virology, Lung pathology, Lung virology, Molecular Sequence Data, Phylogeny, Spain, Spleen pathology, Spleen virology, Chiroptera virology, Disease Reservoirs, Ebolavirus isolation & purification, Hemorrhagic Fever, Ebola veterinary
- Abstract
Filoviruses, amongst the most lethal of primate pathogens, have only been reported as natural infections in sub-Saharan Africa and the Philippines. Infections of bats with the ebolaviruses and marburgviruses do not appear to be associated with disease. Here we report identification in dead insectivorous bats of a genetically distinct filovirus, provisionally named Lloviu virus, after the site of detection, Cueva del Lloviu, in Spain.
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- 2011
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43. SUS1 introns are required for efficient mRNA nuclear export in yeast.
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Cuenca-Bono B, García-Molinero V, Pascual-García P, Dopazo H, Llopis A, Vilardell J, and Rodríguez-Navarro S
- Subjects
- Active Transport, Cell Nucleus, Evolution, Molecular, Exons, Introns, Nonsense Mediated mRNA Decay, Nuclear Proteins metabolism, RNA Splicing, RNA-Binding Proteins metabolism, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins metabolism, Cell Nucleus metabolism, Gene Expression Regulation, Fungal, Nuclear Proteins genetics, RNA, Messenger metabolism, RNA-Binding Proteins genetics, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins genetics
- Abstract
Efficient coupling between mRNA synthesis and export is essential for gene expression. Sus1/ENY2, a component of the SAGA and TREX-2 complexes, is involved in both transcription and mRNA export. While most yeast genes lack introns, we previously reported that yeast SUS1 bears two. Here we show that this feature is evolutionarily conserved and critical for Sus1 function. We determine that while SUS1 splicing is inefficient, it responds to cellular conditions, and intronic mutations either promoting or blocking splicing lead to defects in mRNA export and cell growth. Consistent with this, we find that an intron-less SUS1 only partially rescues sus1Δ phenotypes. Remarkably, splicing of each SUS1 intron is also affected by the presence of the other and by SUS1 exonic sequences. Moreover, by following SUS1 RNA and protein levels we establish that nonsense-mediated decay (NMD) pathway and the splicing factor Mud2 both play a role in SUS1 expression. Our data (and those of the accompanying work by Hossain et al.) provide evidence of the involvement of splicing, translation, and decay in the regulation of early events in mRNP biogenesis; and imply the additional requirement for a balance in splicing isoforms from a single gene.
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- 2011
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44. Role of tomato BRANCHED1-like genes in the control of shoot branching.
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Martín-Trillo M, Grandío EG, Serra F, Marcel F, Rodríguez-Buey ML, Schmitz G, Theres K, Bendahmane A, Dopazo H, and Cubas P
- Subjects
- Amino Acid Sequence, Chromosome Mapping, Evolution, Molecular, Gene Duplication, Solanum lycopersicum genetics, Solanum lycopersicum metabolism, Solanum lycopersicum ultrastructure, Molecular Sequence Data, Mutation, Phenotype, Phylogeny, Plant Leaves genetics, Plant Leaves growth & development, Plant Leaves metabolism, Plant Leaves ultrastructure, Plant Proteins genetics, Plant Shoots genetics, Plant Shoots metabolism, Plant Shoots ultrastructure, Plants, Genetically Modified genetics, Plants, Genetically Modified growth & development, Plants, Genetically Modified metabolism, Plants, Genetically Modified ultrastructure, Point Mutation, RNA, Messenger genetics, Sequence Alignment, Transcription Factors genetics, Transcription Factors metabolism, Gene Expression Regulation, Plant physiology, Solanum lycopersicum growth & development, Plant Proteins metabolism, Plant Shoots growth & development
- Abstract
In angiosperms, shoot branching greatly determines overall plant architecture and affects fundamental aspects of plant life. Branching patterns are determined by genetic pathways conserved widely across angiosperms. In Arabidopsis thaliana (Brassicaceae, Rosidae) BRANCHED1 (BRC1) plays a central role in this process, acting locally to arrest axillary bud growth. In tomato (Solanum lycopersicum, Solanaceae, Asteridae) we have identified two BRC1-like paralogues, SlBRC1a and SlBRC1b. These genes are expressed in arrested axillary buds and both are down-regulated upon bud activation, although SlBRC1a is transcribed at much lower levels than SlBRC1b. Alternative splicing of SlBRC1a renders two transcripts that encode two BRC1-like proteins with different C-t domains due to a 3'-terminal frameshift. The phenotype of loss-of-function lines suggests that SlBRC1b has retained the ancestral role of BRC1 in shoot branch suppression. We have isolated the BRC1a and BRC1b genes of other Solanum species and have studied their evolution rates across the lineages. These studies indicate that, after duplication of an ancestral BRC1-like gene, BRC1b genes continued to evolve under a strong purifying selection that was consistent with the conserved function of SlBRC1b in shoot branching control. In contrast, the coding sequences of Solanum BRC1a genes have evolved at a higher evolution rate. Branch-site tests indicate that this difference does not reflect relaxation but rather positive selective pressure for adaptation., (© 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.)
- Published
- 2011
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45. Phylogenetic and in silico structural analysis of the Parkinson disease-related kinase PINK1.
- Author
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Cardona F, Sánchez-Mut JV, Dopazo H, and Pérez-Tur J
- Subjects
- Base Sequence, Humans, Molecular Sequence Data, Protein Conformation, Sequence Alignment, Parkinson Disease genetics, Phylogeny, Protein Kinases genetics
- Abstract
Parkinson disease (PD) is the second most common neurodegenerative disorder and is characterized by the loss of dopaminergic neurons in the substantia nigra. Mutations in PINK1 were shown to cause recessive familial PD, and today are proposed to be associated with the disease via mitochondrial dysfunction and oxidative damage. The PINK1 gene comprises eight exons, which encode a ubiquitously expressed 581 amino acid protein that contains an N-terminal mitochondrial targeting domain and a serine/threonine protein kinase. To better understand the relationship between PINK1 and PD we have first analyzed the evolutionary history of the gene showing its late emergence in evolution. In addition, we have modeled the three-dimensional structure of PINK1 and found some evidences that help to explain the effect of some PD-related mutations in this protein's function., (© 2011 Wiley-Liss, Inc.)
- Published
- 2011
- Full Text
- View/download PDF
46. Natural selection on functional modules, a genome-wide analysis.
- Author
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Serra F, Arbiza L, Dopazo J, and Dopazo H
- Subjects
- Animals, Databases, Genetic, Drosophila genetics, Genome, Insect, Mammals genetics, Phylogeny, Sequence Analysis, DNA, Genome-Wide Association Study, Genomics, Selection, Genetic
- Abstract
Classically, the functional consequences of natural selection over genomes have been analyzed as the compound effects of individual genes. The current paradigm for large-scale analysis of adaptation is based on the observed significant deviations of rates of individual genes from neutral evolutionary expectation. This approach, which assumed independence among genes, has not been able to identify biological functions significantly enriched in positively selected genes in individual species. Alternatively, pooling related species has enhanced the search for signatures of selection. However, grouping signatures does not allow testing for adaptive differences between species. Here we introduce the Gene-Set Selection Analysis (GSSA), a new genome-wide approach to test for evidences of natural selection on functional modules. GSSA is able to detect lineage specific evolutionary rate changes in a notable number of functional modules. For example, in nine mammal and Drosophilae genomes GSSA identifies hundreds of functional modules with significant associations to high and low rates of evolution. Many of the detected functional modules with high evolutionary rates have been previously identified as biological functions under positive selection. Notably, GSSA identifies conserved functional modules with many positively selected genes, which questions whether they are exclusively selected for fitting genomes to environmental changes. Our results agree with previous studies suggesting that adaptation requires positive selection, but not every mutation under positive selection contributes to the adaptive dynamical process of the evolution of species.
- Published
- 2011
- Full Text
- View/download PDF
47. Recent human evolution has shaped geographical differences in susceptibility to disease.
- Author
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Marigorta UM, Lao O, Casals F, Calafell F, Morcillo-Suárez C, Faria R, Bosch E, Serra F, Bertranpetit J, Dopazo H, and Navarro A
- Subjects
- Asian People, Biological Evolution, Genetic Variation genetics, Genome, Human genetics, Genome-Wide Association Study, Humans, White People, Genetic Predisposition to Disease genetics
- Abstract
Background: Searching for associations between genetic variants and complex diseases has been a very active area of research for over two decades. More than 51,000 potential associations have been studied and published, a figure that keeps increasing, especially with the recent explosion of array-based Genome-Wide Association Studies. Even if the number of true associations described so far is high, many of the putative risk variants detected so far have failed to be consistently replicated and are widely considered false positives. Here, we focus on the world-wide patterns of replicability of published association studies., Results: We report three main findings. First, contrary to previous results, genes associated to complex diseases present lower degrees of genetic differentiation among human populations than average genome-wide levels. Second, also contrary to previous results, the differences in replicability of disease associated-loci between Europeans and East Asians are highly correlated with genetic differentiation between these populations. Finally, highly replicated genes present increased levels of high-frequency derived alleles in European and Asian populations when compared to African populations., Conclusions: Our findings highlight the heterogeneous nature of the genetic etiology of complex disease, confirm the importance of the recent evolutionary history of our species in current patterns of disease susceptibility and could cast doubts on the status as false positives of some associations that have failed to replicate across populations.
- Published
- 2011
- Full Text
- View/download PDF
48. Sexual selection halts the relaxation of protamine 2 among rodents.
- Author
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Lüke L, Vicens A, Serra F, Luque-Larena JJ, Dopazo H, Roldan ER, and Gomendio M
- Subjects
- Amino Acid Sequence, Animals, Biological Evolution, Molecular Sequence Data, Polymerase Chain Reaction, Protamines chemistry, Rodentia, Sequence Homology, Amino Acid, Protamines metabolism, Sexual Behavior, Animal
- Abstract
Sexual selection has been proposed as the driving force promoting the rapid evolutionary changes observed in some reproductive genes including protamines. We test this hypothesis in a group of rodents which show marked differences in the intensity of sexual selection. Levels of sperm competition were not associated with the evolutionary rates of protamine 1 but, contrary to expectations, were negatively related to the evolutionary rate of cleaved- and mature-protamine 2. Since both domains were found to be under relaxation, our findings reveal an unforeseen role of sexual selection: to halt the degree of degeneration that proteins within families may experience due to functional redundancy. The degree of relaxation of protamine 2 in this group of rodents is such that in some species it has become dysfunctional and it is not expressed in mature spermatozoa. In contrast, protamine 1 is functionally conserved but shows directed positive selection on specific sites which are functionally relevant such as DNA-anchoring domains and phosphorylation sites. We conclude that in rodents protamine 2 is under relaxation and that sexual selection removes deleterious mutations among species with high levels of sperm competition to maintain the protein functional and the spermatozoa competitive., (© 2011 Lüke et al.)
- Published
- 2011
- Full Text
- View/download PDF
49. Genome-wide heterogeneity of nucleotide substitution model fit.
- Author
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Arbiza L, Patricio M, Dopazo H, and Posada D
- Subjects
- Animals, Drosophila genetics, Evolution, Molecular, Mammals genetics, Mutation, Open Reading Frames genetics, Sequence Alignment, Vertebrates genetics, Genome, Models, Genetic, Nucleotides genetics, Phylogeny
- Abstract
At a genomic scale, the patterns that have shaped molecular evolution are believed to be largely heterogeneous. Consequently, comparative analyses should use appropriate probabilistic substitution models that capture the main features under which different genomic regions have evolved. While efforts have concentrated in the development and understanding of model selection techniques, no descriptions of overall relative substitution model fit at the genome level have been reported. Here, we provide a characterization of best-fit substitution models across three genomic data sets including coding regions from mammals, vertebrates, and Drosophila (24,000 alignments). According to the Akaike Information Criterion (AIC), 82 of 88 models considered were selected as best-fit models at least in one occasion, although with very different frequencies. Most parameter estimates also varied broadly among genes. Patterns found for vertebrates and Drosophila were quite similar and often more complex than those found in mammals. Phylogenetic trees derived from models in the 95% confidence interval set showed much less variance and were significantly closer to the tree estimated under the best-fit model than trees derived from models outside this interval. Although alternative criteria selected simpler models than the AIC, they suggested similar patterns. All together our results show that at a genomic scale, different gene alignments for the same set of taxa are best explained by a large variety of different substitution models and that model choice has implications on different parameter estimates including the inferred phylogenetic trees. After taking into account the differences related to sample size, our results suggest a noticeable diversity in the underlying evolutionary process. All together, we conclude that the use of model selection techniques is important to obtain consistent phylogenetic estimates from real data at a genomic scale.
- Published
- 2011
- Full Text
- View/download PDF
50. Sexual selection drives weak positive selection in protamine genes and high promoter divergence, enhancing sperm competitiveness.
- Author
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Martin-Coello J, Dopazo H, Arbiza L, Ausió J, Roldan ER, and Gomendio M
- Subjects
- Adaptation, Biological, Animals, Evolution, Molecular, Female, Fertilization, Male, Mice, Phenotype, Phylogeny, Protamines chemistry, Sequence Analysis, DNA, Species Specificity, Sperm Motility, Spermatozoa cytology, Genetic Variation, Mating Preference, Animal, Promoter Regions, Genetic, Protamines genetics, Selection, Genetic, Spermatozoa physiology
- Abstract
Phenotypic adaptations may be the result of changes in gene structure or gene regulation, but little is known about the evolution of gene expression. In addition, it is unclear whether the same selective forces may operate at both levels simultaneously. Reproductive proteins evolve rapidly, but the underlying selective forces promoting such rapid changes are still a matter of debate. In particular, the role of sexual selection in driving positive selection among reproductive proteins remains controversial, whereas its potential influence on changes in promoter regions has not been explored. Protamines are responsible for maintaining DNA in a compacted form in chromosomes in sperm and the available evidence suggests that they evolve rapidly. Because protamines condense DNA within the sperm nucleus, they influence sperm head shape. Here, we examine the influence of sperm competition upon protamine 1 and protamine 2 genes and their promoters, by comparing closely related species of Mus that differ in relative testes size, a reliable indicator of levels of sperm competition. We find evidence of positive selection in the protamine 2 gene in the species with the highest inferred levels of sperm competition. In addition, sperm competition levels across all species are strongly associated with high divergence in protamine 2 promoters that, in turn, are associated with sperm swimming speed. We suggest that changes in protamine 2 promoters are likely to enhance sperm swimming speed by making sperm heads more hydrodynamic. Such phenotypic changes are adaptive because sperm swimming speed may be a major determinant of fertilization success under sperm competition. Thus, when species have diverged recently, few changes in gene-coding sequences are found, while high divergence in promoters seems to be associated with the intensity of sexual selection.
- Published
- 2009
- Full Text
- View/download PDF
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