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  1. Article ; Online: Genetic ancestry effects on the response to viral infection are pervasive but cell type specific.

    Randolph, Haley E / Fiege, Jessica K / Thielen, Beth K / Mickelson, Clayton K / Shiratori, Mari / Barroso-Batista, João / Langlois, Ryan A / Barreiro, Luis B

    Science (New York, N.Y.)

    2021  Volume 374, Issue 6571, Page(s) 1127–1133

    Abstract: Humans differ in their susceptibility to infectious disease, partly owing to variation in the immune response after infection. We used single-cell RNA sequencing to quantify variation in the response to influenza infection in peripheral blood mononuclear ...

    Abstract Humans differ in their susceptibility to infectious disease, partly owing to variation in the immune response after infection. We used single-cell RNA sequencing to quantify variation in the response to influenza infection in peripheral blood mononuclear cells from European- and African-ancestry males. Genetic ancestry effects are common but highly cell type specific. Higher levels of European ancestry are associated with increased type I interferon pathway activity in early infection, which predicts reduced viral titers at later time points. Substantial population-associated variation is explained by cis
    MeSH term(s) Adult ; Black or African American/genetics ; Aged ; COVID-19/genetics ; COVID-19/immunology ; COVID-19/physiopathology ; Disease Susceptibility ; Gene Expression Regulation ; Genetic Variation ; Humans ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza A Virus, H1N1 Subtype/physiology ; Influenza, Human/genetics ; Influenza, Human/immunology ; Interferon Type I/immunology ; Interferon Type I/metabolism ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/virology ; Male ; Middle Aged ; Quantitative Trait Loci ; Severity of Illness Index ; Single-Cell Analysis ; Transcription, Genetic ; Viral Load ; White People/genetics ; Young Adult
    Chemical Substances Interferon Type I
    Language English
    Publishing date 2021-11-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abg0928
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Adaptive immunity increases the pace and predictability of evolutionary change in commensal gut bacteria.

    Barroso-Batista, João / Demengeot, Jocelyne / Gordo, Isabel

    Nature communications

    2015  Volume 6, Page(s) 8945

    Abstract: Co-evolution between the mammalian immune system and the gut microbiota is believed to have shaped the microbiota's astonishing diversity. Here we test the corollary hypothesis that the adaptive immune system, directly or indirectly, influences the ... ...

    Abstract Co-evolution between the mammalian immune system and the gut microbiota is believed to have shaped the microbiota's astonishing diversity. Here we test the corollary hypothesis that the adaptive immune system, directly or indirectly, influences the evolution of commensal species. We compare the evolution of Escherichia coli upon colonization of the gut of wild-type and Rag2(-/-) mice, which lack lymphocytes. We show that bacterial adaptation is slower in immune-compromised animals, a phenomenon explained by differences in the action of natural selection within each host. Emerging mutations exhibit strong beneficial effects in healthy hosts but substantial antagonistic pleiotropy in immune-deficient mice. This feature is due to changes in the composition of the gut microbiota, which differs according to the immune status of the host. Our results indicate that the adaptive immune system influences the tempo and predictability of E. coli adaptation to the mouse gut.
    MeSH term(s) Adaptive Immunity ; Animals ; Biological Evolution ; Escherichia coli/genetics ; Escherichia coli/growth & development ; Escherichia coli/physiology ; Female ; Gastrointestinal Microbiome ; Gastrointestinal Tract/immunology ; Gastrointestinal Tract/microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Symbiosis
    Language English
    Publishing date 2015-11-30
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/ncomms9945
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Recurrent Reverse Evolution Maintains Polymorphism after Strong Bottlenecks in Commensal Gut Bacteria.

    Sousa, Ana / Ramiro, Ricardo S / Barroso-Batista, João / Güleresi, Daniela / Lourenço, Marta / Gordo, Isabel

    Molecular biology and evolution

    2017  Volume 34, Issue 11, Page(s) 2879–2892

    Abstract: The evolution of new strains within the gut ecosystem is poorly understood. We used a natural but controlled system to follow the emergence of intraspecies diversity of commensal Escherichia coli, during three rounds of adaptation to the mouse gut (∼1, ... ...

    Abstract The evolution of new strains within the gut ecosystem is poorly understood. We used a natural but controlled system to follow the emergence of intraspecies diversity of commensal Escherichia coli, during three rounds of adaptation to the mouse gut (∼1,300 generations). We previously showed that, in the first round, a strongly beneficial phenotype (loss-of-function for galactitol consumption; gat-negative) spread to >90% frequency in all colonized mice. Here, we show that this loss-of-function is repeatedly reversed when a gat-negative clone colonizes new mice. The regain of function occurs via compensatory mutation and reversion, the latter leaving no trace of past adaptation. We further show that loss-of-function adaptive mutants reevolve, after colonization with an evolved gat-positive clone. Thus, even under strong bottlenecks a regime of strong-mutation-strong-selection dominates adaptation. Coupling experiments and modeling, we establish that reverse evolution recurrently generates two coexisting phenotypes within the microbiota that can or not consume galactitol (gat-positive and gat-negative, respectively). Although the abundance of the dominant strain, the gat-negative, depends on the microbiota composition, gat-positive abundance is independent of the microbiota composition and can be precisely manipulated by supplementing the diet with galactitol. These results show that a specific diet is able to change the abundance of specific strains. Importantly, we find polymorphism for these phenotypes in indigenous Enterobacteria of mice and man. Our results demonstrate that natural selection can greatly overwhelm genetic drift at structuring the strain diversity of gut commensals and that competition for limiting resources may be a key mechanism for maintaining polymorphism in the gut.
    MeSH term(s) Adaptation, Physiological/genetics ; Animals ; Bacteria/genetics ; Biological Evolution ; Enterobacteriaceae/genetics ; Escherichia coli/genetics ; Galactitol/genetics ; Galactitol/metabolism ; Gastrointestinal Microbiome/genetics ; Genes, Bacterial/genetics ; Mice ; Polymorphism, Genetic/genetics ; Selection, Genetic/genetics ; Symbiosis/genetics
    Chemical Substances Galactitol (113ZQ1Y7DD)
    Language English
    Publishing date 2017-09-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 998579-7
    ISSN 1537-1719 ; 0737-4038
    ISSN (online) 1537-1719
    ISSN 0737-4038
    DOI 10.1093/molbev/msx221
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2137: Show issues Location:
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  4. Article ; Online: Specific Eco-evolutionary Contexts in the Mouse Gut Reveal Escherichia coli Metabolic Versatility.

    Barroso-Batista, João / Pedro, Miguel F / Sales-Dias, Joana / Pinto, Catarina J G / Thompson, Jessica A / Pereira, Helena / Demengeot, Jocelyne / Gordo, Isabel / Xavier, Karina B

    Current biology : CB

    2020  Volume 30, Issue 6, Page(s) 1049–1062.e7

    Abstract: Members of the gut microbiota are thought to experience strong competition for nutrients. However, how such competition shapes their evolutionary dynamics and depends on intra- and interspecies interactions is poorly understood. Here, we test the ... ...

    Abstract Members of the gut microbiota are thought to experience strong competition for nutrients. However, how such competition shapes their evolutionary dynamics and depends on intra- and interspecies interactions is poorly understood. Here, we test the hypothesis that Escherichia coli evolution in the mouse gut is more predictable across hosts in the absence of interspecies competition than in the presence of other microbial species. In support, we observed that lrp, a gene encoding a global regulator of amino acid metabolism, was repeatedly selected in germ-free mice 2 weeks after mono-colonization by this bacterium. We established that this specific genetic adaptation increased E. coli's ability to compete for amino acids, and analysis of gut metabolites identified serine and threonine as the metabolites preferentially consumed by E. coli in the mono-colonized mouse gut. Preference for serine consumption was further supported by testing a set of mutants that showed loss of advantage of an lrp mutant impaired in serine metabolism in vitro and in vivo. Remarkably, the presence of a single additional member of the microbiota, Blautia coccoides, was sufficient to alter the gut metabolome and, consequently, the evolutionary path of E. coli. In this environment, the fitness advantage of the lrp mutant bacteria is lost, and mutations in genes involved in anaerobic respiration were selected instead, recapitulating the eco-evolutionary context from mice with a complex microbiota. Together, these results highlight the metabolic plasticity and evolutionary versatility of E. coli, tailored to the specific ecology it experiences in the gut.
    MeSH term(s) Animals ; Biological Evolution ; Clostridiales/physiology ; Escherichia coli K12/metabolism ; Gastrointestinal Microbiome ; Male ; Metabolome ; Mice/microbiology ; Mice, Inbred C57BL
    Language English
    Publishing date 2020-03-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2020.01.050
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3208: Show issues Location:
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  5. Article ; Online: A Mutational Hotspot and Strong Selection Contribute to the Order of Mutations Selected for during Escherichia coli Adaptation to the Gut.

    Lourenço, Marta / Ramiro, Ricardo S / Güleresi, Daniela / Barroso-Batista, João / Xavier, Karina B / Gordo, Isabel / Sousa, Ana

    PLoS genetics

    2016  Volume 12, Issue 11, Page(s) e1006420

    Abstract: The relative role of drift versus selection underlying the evolution of bacterial species within the gut microbiota remains poorly understood. The large sizes of bacterial populations in this environment suggest that even adaptive mutations with weak ... ...

    Abstract The relative role of drift versus selection underlying the evolution of bacterial species within the gut microbiota remains poorly understood. The large sizes of bacterial populations in this environment suggest that even adaptive mutations with weak effects, thought to be the most frequently occurring, could substantially contribute to a rapid pace of evolutionary change in the gut. We followed the emergence of intra-species diversity in a commensal Escherichia coli strain that previously acquired an adaptive mutation with strong effect during one week of colonization of the mouse gut. Following this first step, which consisted of inactivating a metabolic operon, one third of the subsequent adaptive mutations were found to have a selective effect as high as the first. Nevertheless, the order of the adaptive steps was strongly affected by a mutational hotspot with an exceptionally high mutation rate of 10-5. The pattern of polymorphism emerging in the populations evolving within different hosts was characterized by periodic selection, which reduced diversity, but also frequency-dependent selection, actively maintaining genetic diversity. Furthermore, the continuous emergence of similar phenotypes due to distinct mutations, known as clonal interference, was pervasive. Evolutionary change within the gut is therefore highly repeatable within and across hosts, with adaptive mutations of selection coefficients as strong as 12% accumulating without strong constraints on genetic background. In vivo competitive assays showed that one of the second steps (focA) exhibited positive epistasis with the first, while another (dcuB) exhibited negative epistasis. The data shows that strong effect adaptive mutations continuously recur in gut commensal bacterial species.
    MeSH term(s) Adaptation, Physiological/genetics ; Alleles ; Animals ; Dicarboxylic Acid Transporters/genetics ; Epistasis, Genetic ; Escherichia coli/genetics ; Escherichia coli/pathogenicity ; Escherichia coli Proteins/genetics ; Evolution, Molecular ; Gastrointestinal Microbiome/genetics ; Genetic Variation ; Membrane Transport Proteins/genetics ; Mice ; Mutation ; Selection, Genetic
    Chemical Substances Dicarboxylic Acid Transporters ; Escherichia coli Proteins ; FocA protein, E coli ; Membrane Transport Proteins ; dcuB protein, E coli
    Language English
    Publishing date 2016-11-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1006420
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The first steps of adaptation of Escherichia coli to the gut are dominated by soft sweeps.

    Barroso-Batista, João / Sousa, Ana / Lourenço, Marta / Bergman, Marie-Louise / Sobral, Daniel / Demengeot, Jocelyne / Xavier, Karina B / Gordo, Isabel

    PLoS genetics

    2014  Volume 10, Issue 3, Page(s) e1004182

    Abstract: The accumulation of adaptive mutations is essential for survival in novel environments. However, in clonal populations with a high mutational supply, the power of natural selection is expected to be limited. This is due to clonal interference--the ... ...

    Abstract The accumulation of adaptive mutations is essential for survival in novel environments. However, in clonal populations with a high mutational supply, the power of natural selection is expected to be limited. This is due to clonal interference--the competition of clones carrying different beneficial mutations--which leads to the loss of many small effect mutations and fixation of large effect ones. If interference is abundant, then mechanisms for horizontal transfer of genes, which allow the immediate combination of beneficial alleles in a single background, are expected to evolve. However, the relevance of interference in natural complex environments, such as the gut, is poorly known. To address this issue, we have developed an experimental system which allows to uncover the nature of the adaptive process as Escherichia coli adapts to the mouse gut. This system shows the invasion of beneficial mutations in the bacterial populations and demonstrates the pervasiveness of clonal interference. The observed dynamics of change in frequency of beneficial mutations are consistent with soft sweeps, where different adaptive mutations with similar phenotypes, arise repeatedly on different haplotypes without reaching fixation. Despite the complexity of this ecosystem, the genetic basis of the adaptive mutations revealed a striking parallelism in independently evolving populations. This was mainly characterized by the insertion of transposable elements in both coding and regulatory regions of a few genes. Interestingly, in most populations we observed a complete phenotypic sweep without loss of genetic variation. The intense clonal interference during adaptation to the gut environment, here demonstrated, may be important for our understanding of the levels of strain diversity of E. coli inhabiting the human gut microbiota and of its recombination rate.
    MeSH term(s) Adaptation, Physiological/genetics ; Alleles ; Animals ; Escherichia coli/genetics ; Escherichia coli/growth & development ; Escherichia coli/pathogenicity ; Genetic Variation ; Humans ; Mice ; Models, Genetic ; Mutation ; Selection, Genetic/genetics ; Stomach/microbiology
    Language English
    Publishing date 2014-03-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1004182
    Database MEDical Literature Analysis and Retrieval System OnLINE

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