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

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

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

PopHumanScan : the online catalog of human genome adaptation

Since the migrations that led humans to colonize Earth, our species has faced frequent adaptive challenges that have left signatures in the landscape of genetic variation and that we can identify in our today-s genomes. Here, we (i) perform an outlier approach on eight different population genetic statistics for 22 non-admixed human populations of the Phase III of the 1000 Genomes Project to detect selective sweeps at different historical ages, as well as events of recurrent positive selection in the human lineage; and (ii) create PopHumanScan, an online catalog that compiles and annotates all candidate regions under selection to facilitate their validation and thoroughly analysis. Well-known examples of human genetic adaptation published elsewhere are included in the catalog, as well as hundreds of other attractive candidates that will require further investigation. Designed as a collaborative database, PopHumanScan aims to become a central repository to share information, guide future studies and help advance our understanding of how selection has modeled our genomes as a response to changes in the environment or lifestyle of human populations. PopHumanScan is open and freely available at https://pophumanscan.uab.cat

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

Identifiquen més de 800 noves regions del genoma que podrien ser rellevants en l'evolució humana

Un estudi del grup de recerca Bioinformàtica de la Diversitat Genòmica de la UAB, publicat a la revista Nucleic Acids Research, incrementa en un 40% el total dels senyals de selecció natural en el genoma humà detectades fins ara. Els investigadors han aconseguit sumar un total de 873 noves regions del genoma humà com a fermes candidates d'haver estat el blanc de la selecció natural en algun moment des del sorgiment de la nostra espècie fins al present. Aquestes se sumen a les 1986 que ja s'havien detectat fins a la data, proporcionant un conjunt de dades molt valuós per respondre a la pregunta: què ens fa humans? Les dades són fruit del projecte PopHumanScan, un catàleg exhaustiu de regions que mostren evidències de la selecció natural en el genoma humà.Un estudio del grupo de investigación Bioinformática de la Diversidad Genómica de la UAB, publicado en la revista Nucleic Acids Research, incrementa en un 40% el total de las señales de selección natural en el genoma humano detectadas hasta la fecha. Los investigadores han conseguido sumar un total de 873 nuevas regiones del genoma humano como firmes candidatas de haber sido el blanco de la selección natural en algún momento desde el surgimiento de nuestra especie hasta el presente. Estas se suman a las 1986 que ya se habían detectado hasta la fecha, proporcionado un conjunto de datos muy valioso para responder a la pregunta: ¿qué nos hace humanos? Los datos son fruto del proyecto PopHumanScan, un catálogo exhaustivo de regiones que muestran evidencias de la selección natural en el genoma humano.A study by the research group Bioinformatics of Genome Diversity at the Universitat Autònoma de Barcelona (UAB), published in the journal Nucleic Acids Research, increases by 40% the total number of signals of natural selection detected in the human genome to date. Researchers were able to add a total of 873 new regions of the human genome as firm candidates to have been the target of natural selection at some point from the emergence of our species to the present. These are added to the 1986 regions that had already been detected, providing a very valuable set of data to help answer the question: what makes us humans? The data is part of the PopHumanScan project, an exhaustive catalog of regions that show evidence of natural selection in the human genome

Complete mitochondrial DNA profile in stroke : A geographical matched case-control study in Spanish population

Altres ajuts: acords transformatius de la UABIntroduction: Stroke, the second leading cause of death worldwide, is a complex disease influenced by many risk factors among which we can find reactive oxygen species (ROS). Since mitochondria are the main producers of cellular ROS, nowadays studies are trying to elucidate the role of these organelles and its DNA (mtDNA) variation in stroke risk. The aim of the present study was to perform a comprehensive evaluation of the association between mtDNA mutations and mtDNA content and stroke risk. Material and methods: Homoplasmic and heteroplasmic mutations of the mtDNA were analysed in a case-controls study using 110 S cases and their corresponding control individuals. Mitochondrial DNA copy number (mtDNA-CN) was analysed in 73 of those case-control pairs. Results: Our results suggest that haplogroup V, specifically variants m.72C > T, m.4580G > A, m.15904C > T and m.16298 T > C have a protective role in relation to stroke risk. On the contrary, variants m.73A > G, m.11719G > A and m.14766C > T appear to be genetic risk factors for stroke. In this study, we found no statistically significant association between stroke risk and mitochondrial DNA copy number. Conclusions: These results demonstrate the possible role of mtDNA genetics on the pathogenesis of stroke, probably through alterations in mitochondrial ROS production

Drosophila evolution over space and time (DEST):A new population genomics resource

Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome datasets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate datasets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 previously published and unpublished population samples from over 100 locations in > 20 countries on four continents. Several of these locations have been sampled at different seasons across multiple years. This dataset, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental meta-data. A web-based genome browser and web portal provide easy access to the SNP dataset. We further provide guidelines on how to use Pool-Seq data for model-based demographic inference. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan dataset. Our resource will enable population geneticists to analyze spatio-temporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.DrosEU is funded by a Special Topic Networks (STN) grant from the European Society for Evolutionary Biology (ESEB). MK (M. Kapun) was supported by the Austrian Science Foundation (grant no. FWF P32275); JG by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (H2020-ERC-2014-CoG-647900) and by the Spanish Ministry of Science and Innovation (BFU-2011-24397); TF by the Swiss National Science Foundation (SNSF grants PP00P3_133641, PP00P3_165836, and 31003A_182262) and a Mercator Fellowship from the German Research Foundation (DFG), held as a EvoPAD Visiting Professor at the Institute for Evolution and Biodiversity, University of Münster; AOB by the National Institutes of Health (R35 GM119686); MK (M. Kankare) by Academy of Finland grant 322980; VL by Danish Natural Science Research Council (FNU) grant 4002-00113B; FS Deutsche Forschungsgemeinschaft (DFG) grant STA1154/4-1, Project 408908608; JP by the Deutsche Forschungsgemeinschaft Projects 274388701 and 347368302; AU by FPI fellowship (BES-2012-052999); ET Israel Science Foundation (ISF) grant 1737/17; MSV, MSR and MJ by a grant from the Ministry of Education, Science and Technological Development of the Republic of Serbia (451-03-68/2020-14/200178); AP, KE and MT by a grant from the Ministry of Education, Science and Technological Development of the Republic of Serbia (451-03-68/2020-14/200007); and TM NSERC grant RGPIN-2018-05551.Peer reviewe

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality