PDA v.2: improving the exploration and estimation of nucleotide polymorphism in large datasets of heterogeneous DNA

Pipeline Diversity Analysis (PDA) is an open-source, web-based tool that allows the exploration of polymorphism in large datasets of heterogeneous DNA sequences, and can be used to create secondary polymorphism databases for different taxonomic groups, such as the Drosophila Polymorphism Database (DPDB). A new version of the pipeline presented here, PDA v.2, incorporates substantial improvements, including new methods for data mining and grouping sequences, new criteria for data quality assessment and a better user interface. PDA is a powerful tool to obtain and synthesize existing empirical evidence on genetic diversity in any species or species group. PDA v.2 is available on the web at

L'eficiència de la selecció natural

Des del Departament de Genètica i Microbiologia de la Universitat Autònoma de Barcelona, s'ha pogut aprofundir una mica més en l'estudi del canvi evolutiu de les espècies. Partint de la teoria quasi neutra de l'evolució molecular, que emfatitza la importància del factor aleatori de les mutacions genètiques que no aporten beneficis a l'espècie, s'ha demostrat que es pot predir l'eficiència de la selecció natural segons el tamany de la població. Per arribar a aquesta conclusió, l'estudi s'ha realitzat a partir d'anàlisis estadístiques d'una base de dades de diferents espècies de Drosophila, tenint en compte la seva diversitat nucleotídica.Desde el Departamento de Genética y Microbiología de la Universitat Autònoma de Barcelona, se ha podido profundizar un poco más en el estudio del cambio evolutivo de las especies. Partiendo de la teoría casi neutra de la evolución molecular, que enfatiza la importancia del factor aleatorio de las mutaciones genéticas que no aportan beneficios a la especie, se ha demostrado que se puede predecir la eficiencia de la selección natural según el tamaño de la población. Para llegar a esta conclusión, el estudio se ha realizado a partir de análisis estadísticos de una base de datos de diferentes especies de Drosophila, teniendo en cuenta su diversidad nucleotídica

Fast sequence evolution of Hox and Hox-derived genes in the genus Drosophila.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: It is expected that genes that are expressed early in development and have a complex expression pattern are under strong purifying selection and thus evolve slowly. Hox genes fulfill these criteria and thus, should have a low evolutionary rate. However, some observations point to a completely different scenario. Hox genes are usually highly conserved inside the homeobox, but very variable outside it. RESULTS: We have measured the rates of nucleotide divergence and indel fixation of three Hox genes, labial (lab), proboscipedia (pb) and abdominal-A (abd-A), and compared them with those of three genes derived by duplication from Hox3, bicoid (bcd), zerknüllt (zen) and zerknüllt-related (zen2), and 15 non-Hox genes in sets of orthologous sequences of three species of the genus Drosophila. These rates were compared to test the hypothesis that Hox genes evolve slowly. Our results show that the evolutionary rate of Hox genes is higher than that of non-Hox genes when both amino acid differences and indels are taken into account: 43.39% of the amino acid sequence is altered in Hox genes, versus 30.97% in non-Hox genes and 64.73% in Hox-derived genes. Microsatellites scattered along the coding sequence of Hox genes explain partially, but not fully, their fast sequence evolution. CONCLUSION: These results show that Hox genes have a higher evolutionary dynamics than other developmental genes, and emphasize the need to take into account indels in addition to nucleotide substitutions in order to accurately estimate evolutionary rates

MamPol: a database of nucleotide polymorphism in the Mammalia class

Multi-locus and multi-species nucleotide diversity studies would benefit enormously from a public database encompassing high-quality haplotypic sequences with their associated genetic diversity measures. MamPol, ‘Mammalia Polymorphism Database’, is a website containing all the well-annotated polymorphic sequences available in GenBank for the Mammalia class grouped by name of organism and gene. Diversity measures of single nucleotide polymorphisms are provided for each set of haplotypic homologous sequences, including polymorphism at synonymous and non-synonymous sites, linkage disequilibrium and codon bias. Data gathering, calculation of diversity measures and daily updates are automatically performed using PDA software. The MamPol website includes several interfaces for browsing the contents of the database and making customizable comparative searches of different species or taxonomic groups. It also contains a set of tools for simple re-analysis of the available data and a statistics section that is updated daily and summarizes the contents of the database. MamPol is available at and can be downloaded via FTP

Tracen el primer mapa de l'adaptació i la selecció natural de l'anatomia completa d'un embrió

El grup de recerca Bioinformàtica de la Diversitat Genòmica de la UAB, en col·laboració amb el grup de Biologia Evolutiva del Desenvolupament de la Universitat d'Hèlsinki, ha aconseguit cartografiar el primer mapa de l'adaptació i la selecció natural de l'anatomia completa de l'embrió de la mosca de la fruita, l'espècie Drosophila melanogaster. Els autors han seguit una aproximació original que integra macrodades de variació genòmica, d'expressió gènica i del desenvolupament embrionari en aquesta espècie model de la recerca genètica.El grupo de investigación Bioinformática de la Diversidad Genómica de la UAB, en colaboración con el grupo de Biología Evolutiva del Desarrollo de la Universidad de Helsinki, ha conseguido cartografiar el primer mapa de la adaptación y la selección natural de la anatomía completa del embrión de la mosca de la fruta, la especie Drosophila melanogaster. Los autores han seguido una aproximación original que integra macrodatos de variación genómica, de expresión génica y del desarrollo embrionario en esta especie modelo de la investigación genética.The research group Bioinformatics of Genomic Diversity of the UAB, in collaboration with the Evolutionary Development Biology group of the University of Helsinki, have mapped by the first time phenotypic adaptation and natural selection over the complete anatomy of the embryo of the fruit fly, the species Drosophila melanogaster. The authors followed an original approach that integratesgenomic variation, gene expression and embryonic development in this model species of genetic research

PopHuman : navegador de referència de la variació genètica humana

La variació genètica humana és el conjunt de diferències genètiques que distingeixen els nostres genomes, ja sigui entre els individus dins d'una població o entre poblacions. El seu estudi té aplicacions evolutives i mèdiques significatives. El grup de recerca Bioinformàtica de la Diversitat Genòmica de la Universitat Autònoma de Barcelona (UAB), en col·laboració amb científics de l'Institut de Biologia Evolutiva (IBE), ha creat el major inventari disponible de mesures de diversitat genètica al llarg del genoma humà utilitzant les dades del projecte internacional 1000 genomes. Tota la informació s'ha posat a l'abast dels investigadors al navegador genòmic PopHuman. Aquest recurs permet l'anàlisi exhaustiva dels episodis de selecció natural que han tingut lloc al llinatge humà i que han deixat la seva empremta al genoma.La variación genética humana es el conjunto de diferencias genéticas que distinguen nuestros genomas, ya sea entre los individuos dentro de una población o entre poblaciones. Su estudio tiene aplicaciones evolutivas y médicas significativas. El grupo de investigación Bioinformática de la Diversidad Genómica de la Universidad Autónoma de Barcelona (UAB), en colaboración con científicos del Instituto de Biología Evolutiva (IBE), han creado el mayor inventario disponible de medidas de diversidad genética a lo largo del genoma humano. Para ello han utilizado los datos del proyecto internacional 1000 Genomas. Toda la información se ha puesto a disposición de los investigadores en el navegador genómico PopHuman. Este recurso permite el análisis exhaustivo de los episodios de selección natural que han tenido lugar en el linaje humano y han dejado su huella en el genoma.Human genetic variation is the set of genetic differences that distinguish our genomes, either among individuals within a population or between populations. Its study has significant evolutionary and medical applications. The research group Bioinformatics of Genomic Diversity of the Autonomous University of Barcelona (UAB), in collaboration with scientists from the Institute of Evolutionary Biology (IBE), have created the largest available inventory of measures of genetic diversity along the human genome using the data of the international project 1000 Genomes. All the summarized information has been made available to researchers in the PopHuman genomic browser. This resource allows the exhaustive search of episodes of natural selection that have taken place in the human lineage and have left their fingerprint on the genome

Adaptation and Conservation throughout the Drosophila melanogaster Life-Cycle

Previous studies of the evolution of genes expressed at different life-cycle stages of Drosophila melanogaster have not been able to disentangle adaptive from nonadaptive substitutions when using nonsynonymous sites. Here, we overcome this limitation by combining whole-genome polymorphism data from D. melanogaster and divergence data between D. melanogaster and Drosophila yakuba. For the set of genes expressed at different life-cycle stages of D. melanogaster, as reported in modENCODE, we estimate the ratio of substitutions relative to polymorphism between nonsynonymous and synonymous sites (alpha) and then alpha is discomposed into the ratio of adaptive (omega(a)) and nonadaptive (omega(na)) substitutions to synonymous substitutions. We find that the genes expressed in mid- and late-embryonic development are the most conserved, whereas those expressed in early development and postembryonic stages are the least conserved. Importantly, we found that low conservation in early development is due to high rates of nonadaptive substitutions (high omega(na)), whereas in postembryonic stages it is due, instead, to high rates of adaptive substitutions (high omega(a)). By using estimates of different genomic features (codon bias, average intron length, exon number, recombination rate, among others), we also find that genes expressed in mid- and late-embryonic development show the most complex architecture: they are larger, have more exons, more transcripts, and longer introns. In addition, these genes are broadly expressed among all stages. We suggest that all these genomic features are related to the conservation of mid- and late-embryonic development. Globally, our study supports the hourglass pattern of conservation and adaptation over the life-cycle.Peer reviewe

Adaptive evolution is substantially impeded by Hill–Robertson interference in Drosophila

Hill–Robertson interference (HRi) is expected to reduce the efficiency of natural selection when two or more linked selected sites do not segregate freely, but no attempt has been done so far to quantify the overall impact of HRi on the rate of adaptive evolution for any given genome. In this work, we estimate how much HRi impedes the rate of adaptive evolution in the coding genome of Drosophila melanogaster. We compiled a data set of 6,141 autosomal protein-coding genes from Drosophila, from which polymorphism levels in D. melanogaster and divergence out to D. yakuba were estimated. The rate of adaptive evolution was calculated using a derivative of the McDonald–Kreitman test that controls for slightly deleterious mutations. We find that the rate of adaptive amino acid substitution at a given position of the genome is positively correlated to both the rate of recombination and the mutation rate, and negatively correlated to the gene density of the region. These correlations are robust to controlling for each other, for synonymous codon bias and for gene functions related to immune response and testes. We show that HRi diminishes the rate of adaptive evolution by approximately 27%. Interestingly, genes with low mutation rates embedded in gene poor regions lose approximately 17% of their adaptive substitutions whereas genes with high mutation rates embedded in gene rich regions lose approximately 60%. We conclude that HRi hampers the rate of adaptive evolution in Drosophila and that the variation in recombination, mutation, and gene density along the genome affects the HRi effect

IMKT : the integrative McDonald and Kreitman test

The McDonald and Kreitman test (MKT) is one of the most powerful and widely used methods to detect and quantify recurrent natural selection using DNA sequence data. Here we present iMKT (acronym for integrative McDonald and Kreitman test), a novel web-based service performing four distinct MKT types. It allows the detection and estimation of four different selection regimes -adaptive, neutral, strongly deleterious and weakly deleterious- acting on any genomic sequence. iMKT can analyze both user's own population genomic data and pre-loaded Drosophila melanogaster and human sequences of protein-coding genes obtained from the largest population genomic datasets to date. Advanced options in the website allow testing complex hypotheses such as the application example showed here: do genes located in high recombination regions undergo higher rates of adaptation? We aim that iMKT will become a reference site tool for the study of evolutionary adaptation in massive population genomics datasets, especially in Drosophila and humans. iMKT is a free resource online at https://imkt.uab.cat

Revelen l'empremta de la selecció natural al llarg de tot el genoma

Els primers resultats del projecte internacional The Drosophila Genetic Reference Panel, publicats a Nature, tracen per primera vegada el mapa detallat de l'empremta de la selecció natural al llarg de tot el genoma de l'organisme model de la genètica, Drosophila melanogaster. El projecte, amb una participació destacada de la UAB, ha generat una "biblioteca vivent" que permet a qualsevol científic analitzar la relació entre les variacions en el genoma i els trets observables dels individus amb una potència estadística sense precedents, fet que suposa un gran avenç per a l'estudi de les malalties d'origen genètic.Los primeros resultados del proyecto internacional The Drosophila Genetic Reference Panel, publicados en Nature, trazan por primera vez el mapa detallado de la huella de la selección natural a lo largo de todo el genoma del organismo modelo de la genética, Drosophila melanogaster. El proyecto, con una participación destacada de la UAB, ha generado una "biblioteca viviente" que permite a cualquier científico analizar la relación entre las variaciones en el genoma y los rasgos observables de los individuos con una potencia estadística sin precedentes, lo que supone un gran avance para el estudio de las enfermedades de origen genético.The first results of the international project The Drosophila Genetic Reference Panel, published this week in Nature, trace a detailed map of the genomic imprinting of natural selection in the model organism used in the studies of genetics, the Drosophila melanogaster. The project, carried out with notable support from UAB, has generated a "living library" which allows any scientist to analyse the relation between variations in the genome and observable individual traits, with unprecendented statistic strength. This represents a large advance in the study of genetic diseases