BadiRate Software

Podeu consultar l'article relacionat a: http://hdl.handle.net/2445/53350Podeu consultar la pàgina de desenvolupament del programari: http://www.ub.edu/softevol/badirate/BadiRate is a software package to estimate, within a phylogenetic context and by likelihood-based methods (or parsimony): (1) the gain, birth, death and innovation family turnover rates (2) most likely number of family members in internal nodes (3) families with turnover rates higher or lower than that estimated for the whole dat

Mycobacterial Phylogenomics: An Enhanced Method for Gene Turnover Analysis Reveals Uneven Levels of Gene Gain and Loss among Species and Gene Families

Species of the genus Mycobacterium differ in several features, from geographic ranges, and degree of pathogenicity, to ecological and host preferences. The recent availability of several fully sequenced genomes for a number of these species enabled the comparative study of the genetic determinants of this wide lifestyle diversity. Here, we applied two complementary phylogenetic-based approaches using information from 19 Mycobacterium genomes to obtain a more comprehensive view of the evolution of this genus. First, we inferred the phylogenetic relationships using two new approaches, one based on a Mycobacterium-specific amino acid substitution matrix and the other on a gene content dissimilarity matrix. Then, we utilized our recently developed gain-and-death stochastic models to study gene turnover dynamics in this genus in a maximum-likelihood framework. We uncovered a scenario that differs markedly from traditional 16S rRNA data and improves upon recent phylogenomic approaches. We also found that the rates of gene gain and death are high and unevenly distributed both across species and across gene families, further supporting the utility of the new models of rate heterogeneity applied in a phylogenetic context. Finally, the functional annotation of the most expanded or contracted gene families revealed that the transposable elements and the fatty acid metabolism-related gene families are the most important drivers of gene content evolution in Mycobacterium

Genome-wide analysis of adaptive molecular evolution in the carnivorous plant Utricularia gibba

The genome of the bladderwort Utricularia gibba provides an unparalleled opportunity to uncover the adaptive landscape of an aquatic carnivorous plant with unique phenotypic features such as absence of roots, development of water-filled suction bladders, and a highly ramified branching pattern. Despite its tiny size, the U. gibba genome accommodates approximately as many genes as other plant genomes. To examine the relationship between the compactness of its genome and gene turnover, we compared the U. gibba genome with that of four other eudicot species, defining a total of 17,324 gene families (orthogroups). These families were further classified as either 1) lineage-specific expanded/contracted or 2) stable in size. The U. gibba-expanded families are generically related to three main phenotypic features: 1) trap physiology, 2) key plant morphogenetic/developmental pathways, and 3) response to environmental stimuli, including adaptations to life in aquatic environments. Further scans for signatures of protein functional specialization permitted identification of seven candidate genes with amino acid changes putatively fixed by positive Darwinian selection in the U. gibba lineage. The Arabidopsis orthologs of these genes (AXR, UMAMIT41, IGS, TAR2, SOL1, DEG9, and DEG10) are involved in diverse plant biological functions potentially relevant for U. gibba phenotypic diversification, including 1) auxin metabolism and signal transduction, 2) flowering induction and floral meristem transition, 3) root development, and 4) peptidases. Taken together, our results suggest numerous candidate genes and gene families as interesting targets for further experimental confirmation of their functional and adaptive roles in the U. gibba's unique lifestyle and highly specialized body plan

Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers

Genome of the pitcher plant <i>Cephalotus </i>reveals genetic changes associated with carnivory

Carnivorous plants exploit animals as a nutritional source and have inspired long-standing questions about the origin and evolution of carnivory-related traits. To investigate the molecular bases of carnivory, we sequenced the genome of the heterophyllous pitcher plant Cephalotus follicularis, in which we succeeded in regulating the developmental switch between carnivorous and non-carnivorous leaves. Transcriptome comparison of the two leaf types and gene repertoire analysis identified genetic changes associated with prey attraction, capture, digestion and nutrient absorption. Analysis of digestive fluid proteins from C. follicularis and three other carnivorous plants with independent carnivorous origins revealed repeated co-options of stress-responsive protein lineages coupled with convergent amino acid substitutions to acquire digestive physiology. These results imply constraints on the available routes to evolve plant carnivory

Genómica evolutiva de la regulación transcripcional en las principales familias multigénicas del sistema quimiosensorial de Drosophila

[spa] El sistema quimiosensorial (SQ) participa en la detección de nutrientes, depredadores y pareja, siendo -por tanto- fundamental en la supervivencia de los organismos y de las especies. En insectos, las primeras etapas de la quimiopercepción están mediadas por familias multigénicas que codifican: (i) proteínas extracelulares, como las Odorant-Binding Proteins (OBPs) y las Chemosensory Proteins (CSPs); (ii) proteínas quimiorreceptoras, como los Odorant (ORs), Gustatory (GRs) e Ionotropic Receptors (IRs). Dado que la eficacia biológica de los individuos depende de su correcta expresión, estas familias multigénicas constituyen un excelente modelo para estudiar procesos adaptativos a nivel molecular. La creciente disponibilidad de datos moleculares nos ha conferido la oportunidad de comprender el papel de la selección natural en la evolución transcripcional de los genes del SQ. No obstante, la naturaleza masiva e innovadora de estos datos ha hecho indispensable el desarrollo e implementación de nuevos métodos de genética de poblaciones y evolución molecular en las potentes herramientas bioinformáticas DnaSPv5, BadiRate y popDrowser. Utilizando éstas y otras herramientas, hemos determinado que los genes que codifican OBPs no están distribuidos aleatoriamente en el genoma de Drosophila, sino agrupados formando clústeres de genes. La conservación de estos clústeres está relacionada con la amplitud y el ruido transcripcional de sus integrantes, así como también con su estado de la cromatina (’transcription elongation’ y con la unión de la proteína JIL-1). Entre otras funciones, la JIL-1 libera la ARN polimerasa pausada en la región promotora, lo que produce una ráfaga de elongación de la transcripción génica que incrementa el ruido transcripcional. Debido a que las fluctuaciones de OBPs pueden alterar el comportamiento de los individuos, este ruido transcripcional puede generar una plasticidad fenotípica beneficiosa, especialmente en ambientes externos cambiantes. La arquitectura de la región promotora puede jugar un papel fundamental en pausar la actividad de la ARN polimerasa. En este sentido, hemos inferido que las regiones upstream de los aIRs y las CSPs están sometidas a una importante constricción funcional, mientras que las de los ORs y los GRs han experimentado un mayor impacto de la selección darwiniana. Aunque aún faltan más evidencias al respecto, la evolución de las regiones upstream de las OBPs podría estar vinculada con el impacto diferencial de la cromatina en su regulación transcripcional. De cualquier modo, no cabe duda que la selección natural (negativa y positiva) ha contribuido significativamente a la evolución transcripcional de las principales familias multigénicas del SQ, mediante los mecanismos que implican elementos cis-reguladores y estados de la cromatina.[eng] The chemosensory system is involved in the detection of food, predators and mates, being thus essential for the species survival. In insects, the first steps of chemoperception are mediated by multigene families encoding: (i) extracellular proteins, such as Odorant-Binding Proteins (OBPs) and Chemosensory Proteins (CSPs), as well as (ii) chemoreceptors, such as Odorant (ORs), Gustatory (GRs) and Ionotropic Receptors (IRs). Since the fitness of individuals depends on their correct expression, these multigene families are an excellent model to study adaptive processes at the molecular level. The increasing availability of molecular data gives us the opportunity to understand the role of natural selection in the transcriptional regulation of the chemosensory genes. However, the massive and innovative nature of these data makes crucial the development and implementation of new methods for population genetics and molecular evolution in powerful bioinformatics tools, such as DnaSPv5, popDrowser and BadiRate. Using these and other tools, we determined that genes encoding OBPs are clustered along the Drosophila genome. The conservation of these clusters is related to the transcriptional amplitude and noise of their members, as well as to its chromatin state ('transcription elongation' and binding of JIL-1 protein). Among other functions, the JIL-1 releases the RNA polymerase paused at the promoter region, inducing a transcriptional elongation burst that increases expression noise. Because OBPs fluctuations can alter the behavior of individuals, this noise can generate a beneficial phenotypic plasticity, especially in changing external environments. The architecture of the promoter region can play a key role in the RNA polymerase pausing. In this regard, we have inferred that the upstream regions of aIRS and CSPs are under strong functional constraints, whereas Darwinian selection is more pervasive at the ORs and GRs upstream regions. Although further studies are needed, the evolution of the OBP upstream regions may be linked to the differential impact of the high-order chromatin regulatory mechanisms in the OBP transcription. Anyway, it is certain that natural selection (negative and positive) has significantly contributed to the transcriptional evolution of the major chemosensory multigene families, through mechanisms involving cis- regulatory elements and high-order chromatin states

DnaSP v5: A software for comprehensive analysis of DNA polymorphism data

Podeu consultar el programari a: http://hdl.handle.net/2445/53451DnaSP is a software package for a comprehensive analysis of DNA polymorphism data. Version 5 implements a number of new features and analytical methods allowing extensive DNA polymorphism analyses on large datasets. Among other features, the newly implemented methods allow for: (i) analyses on multiple data files; (ii) haplotype phasing; (iii) analyses on insertion/deletion polymorphism data; (iv) visualizing sliding window results integrated with available genome annotations in the UCSC browser

Uncovering the functional constraints underlying the genomic organisation of the Odorant-Binding Protein genes

Animal olfactory systems have a critical role for the survival and reproduction of individuals. In insects, the odorant-binding proteins (OBPs) are encoded by a moderately sized gene family, and mediate the first steps of the olfactory processing. Most OBPs are organized in clusters of a few paralogs, which are conserved over time. Currently, the biological mechanism explaining the close physical proximity among OBPs is not yet established. Here, we conducted a comprehensive study aiming to gain insights into the mechanisms underlying the OBP genomic organization. We found that the OBP clusters are embedded within large conserved arrangements. These organizations also include other non-OBP genes, which often encode proteins integral to plasma membrane. Moreover, the conservation degree of such large clusters is related to the following: 1) the promoter architecture of the confined genes, 2) a characteristic transcriptional environment, and 3) the chromatin conformation of the chromosomal region. Our results suggest that chromatin domains may restrict the location of OBP genes to regions having the appropriate transcriptional environment, leading to the OBP cluster structure. However, the appropriate transcriptional environment for OBP and the other neighbor genes is not dominated by reduced levels of expression noise. Indeed, the stochastic fluctuations in the OBP transcript abundance may have a critical role in the combinatorial nature of the olfactory coding process

BadiRate Software

Podeu consultar l'article relacionat a: http://hdl.handle.net/2445/53350Podeu consultar la pàgina de desenvolupament del programari: http://www.ub.edu/softevol/badirate/BadiRate is a software package to estimate, within a phylogenetic context and by likelihood-based methods (or parsimony): (1) the gain, birth, death and innovation family turnover rates (2) most likely number of family members in internal nodes (3) families with turnover rates higher or lower than that estimated for the whole dat