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Publications in peer reviewed journals

8 Publications found
  • The origin and evolution of cell types.

    Arendt D, Musser JM, Baker CV, Bergman A, Cepko C, Erwin DH, Pavličev M, Schlosser G, Widder S, Laubichler MD, Wagner GP
    2016 - Nat. Rev. Genet., 12: 744-757


    Cell types are the basic building blocks of multicellular organisms and are extensively diversified in animals. Despite recent advances in characterizing cell types, classification schemes remain ambiguous. We propose an evolutionary definition of a cell type that allows cell types to be delineated and compared within and between species. Key to cell type identity are evolutionary changes in the 'core regulatory complex' (CoRC) of transcription factors, that make emergent sister cell types distinct, enable their independent evolution and regulate cell type-specific traits termed apomeres. We discuss the distinction between developmental and evolutionary lineages, and present a roadmap for future research.

  • Biogeographic variation in the microbiome of the ecologically important sponge, Carteriospongia foliascens.

    Luter HM, Widder S, Botté ES, Abdul Wahab M, Whalan S, Moitinho-Silva L, Thomas T, Webster NS
    2015 - PeerJ, e1435


    Sponges are well known for hosting dense and diverse microbial communities, but how these associations vary with biogeography and environment is less clear. Here we compared the microbiome of an ecologically important sponge species, Carteriospongia foliascens, over a large geographic area and identified environmental factors likely responsible for driving microbial community differences between inshore and offshore locations using co-occurrence networks (NWs). The microbiome of C. foliascens exhibited exceptionally high microbial richness, with more than 9,000 OTUs identified at 97% sequence similarity. A large biogeographic signal was evident at the OTU level despite similar phyla level diversity being observed across all geographic locations. The C. foliascens bacterial community was primarily comprised of Gammaproteobacteria (34.2% ± 3.4%) and Cyanobacteria (32.2% ± 3.5%), with lower abundances of Alphaproteobacteria, Bacteroidetes, unidentified Proteobacteria, Actinobacteria, Acidobacteria and Deltaproteobacteria. Co-occurrence NWs revealed a consistent increase in the proportion of Cyanobacteria over Bacteroidetes between turbid inshore and oligotrophic offshore locations, suggesting that the specialist microbiome of C. foliascens is driven by environmental factors.

  • Wiring for independence: positive feedback motifs facilitate individuation of traits in development and evolution.

    Pavličev M, Widder S
    2015 - J. Exp. Zool. B Mol. Dev. Evol., 2: 104-13


    Independent selection response of a trait is contingent on the availability of genetic variation that is not entangled with other traits. Mechanistically, such variational individuation in spite of shared genome results from gene regulation. Changes that increase individuation of traits are likely caused by gene regulatory changes. Yet the effect of regulatory evolution on population variation is understudied. Trait individuation also occurs during development. Developmental differentiation involves two stages-induction of differentiation and the maintenance of differentiated fate. The corresponding gene regulatory transition involves the feed-forward and the regulated feedback motifs. Here we consider analogous transition pattern at the evolutionary scale, establishing an autonomous regulatory sub-network involved in the independent trait variation. A population genetic simulation of regulated feedback loop dynamics under small perturbations shows a decoupling of variation in gene expression between the upstream gene and the responding downstream gene. We furthermore observe that the ranges of dynamics that can be generated by feedback and feed-forward networks overlap. Such phenotypic overlap enables genetic accessibility of network-specific expression dynamics. We suggest that feedback topology may eventually confer selective advantage leading from a gradual process to threshold individuation, i.e., the emergence of a novel trait.

  • Fluvial network organization imprints on microbial co-occurrence networks.

    Widder S, Besemer K, Singer GA, Ceola S, Bertuzzo E, Quince C, Sloan WT, Rinaldo A, Battin TJ
    2014 - Proc. Natl. Acad. Sci. U.S.A., 35: 12799-804


    Recent studies highlight linkages among the architecture of ecological networks, their persistence facing environmental disturbance, and the related patterns of biodiversity. A hitherto unresolved question is whether the structure of the landscape inhabited by organisms leaves an imprint on their ecological networks. We analyzed, based on pyrosequencing profiling of the biofilm communities in 114 streams, how features inherent to fluvial networks affect the co-occurrence networks that the microorganisms form in these biofilms. Our findings suggest that hydrology and metacommunity dynamics, both changing predictably across fluvial networks, affect the fragmentation of the microbial co-occurrence networks throughout the fluvial network. The loss of taxa from co-occurrence networks demonstrates that the removal of gatekeepers disproportionately contributed to network fragmentation, which has potential implications for the functions biofilms fulfill in stream ecosystems. Our findings are critical because of increased anthropogenic pressures deteriorating stream ecosystem integrity and biodiversity.

  • Metagenomic analysis reveals presence of Treponema denticola in a tissue biopsy of the Iceman.

    Maixner F, Thomma A, Cipollini G, Widder S, Rattei T, Zink A
    2014 - PloS one, 6: e99994


    Ancient hominoid genome studies can be regarded by definition as metagenomic analyses since they represent a mixture of both hominoid and microbial sequences in an environment. Here, we report the molecular detection of the oral spirochete Treponema denticola in ancient human tissue biopsies of the Iceman, a 5,300-year-old Copper Age natural ice mummy. Initially, the metagenomic data of the Iceman's genomic survey was screened for bacterial ribosomal RNA (rRNA) specific reads. Through ranking the reads by abundance a relatively high number of rRNA reads most similar to T. denticola was detected. Mapping of the metagenome sequences against the T. denticola genome revealed additional reads most similar to this opportunistic pathogen. The DNA damage pattern of specifically mapped reads suggests an ancient origin of these sequences. The haematogenous spread of bacteria of the oral microbiome often reported in the recent literature could already explain the presence of metagenomic reads specific for T. denticola in the Iceman's bone biopsy. We extended, however, our survey to an Iceman gingival tissue sample and a mouth swab sample and could thereby detect T. denticola and Porphyrimonas gingivalis, another important member of the human commensal oral microflora. Taken together, this study clearly underlines the opportunity to detect disease-associated microorganisms when applying metagenomics-enabled approaches on datasets of ancient human remains.

  • Deciphering microbial interactions and detecting keystone species with co-occurrence networks.

    Berry D, Widder S
    2014 - Front Microbiol, 219


    Co-occurrence networks produced from microbial survey sequencing data are frequently used to identify interactions between community members. While this approach has potential to reveal ecological processes, it has been insufficiently validated due to the technical limitations inherent in studying complex microbial ecosystems. Here, we simulate multi-species microbial communities with known interaction patterns using generalized Lotka-Volterra dynamics. We then construct co-occurrence networks and evaluate how well networks reveal the underlying interactions and how experimental and ecological parameters can affect network inference and interpretation. We find that co-occurrence networks can recapitulate interaction networks under certain conditions, but that they lose interpretability when the effects of habitat filtering become significant. We demonstrate that networks suffer from local hot spots of spurious correlation in the neighborhood of hub species that engage in many interactions. We also identify topological features associated with keystone species in co-occurrence networks. This study provides a substantiated framework to guide environmental microbiologists in the construction and interpretation of co-occurrence networks from microbial survey datasets.

  • Ultra deep sequencing of Listeria monocytogenes sRNA transcriptome revealed new antisense RNAs.

    Behrens S, Widder S, Mannala GK, Qing X, Madhugiri R, Kefer N, Abu Mraheil M, Rattei T, Hain T
    2014 - PloS one, 2: e83979


    Listeria monocytogenes, a gram-positive pathogen, and causative agent of listeriosis, has become a widely used model organism for intracellular infections. Recent studies have identified small non-coding RNAs (sRNAs) as important factors for regulating gene expression and pathogenicity of L. monocytogenes. Increased speed and reduced costs of high throughput sequencing (HTS) techniques have made RNA sequencing (RNA-Seq) the state-of-the-art method to study bacterial transcriptomes. We created a large transcriptome dataset of L. monocytogenes containing a total of 21 million reads, using the SOLiD sequencing technology. The dataset contained cDNA sequences generated from L. monocytogenes RNA collected under intracellular and extracellular condition and additionally was size fractioned into three different size ranges from <40 nt, 40-150 nt and >150 nt. We report here, the identification of nine new sRNAs candidates of L. monocytogenes and a reevaluation of known sRNAs of L. monocytogenes EGD-e. Automatic comparison to known sRNAs revealed a high recovery rate of 55%, which was increased to 90% by manual revision of the data. Moreover, thorough classification of known sRNAs shed further light on their possible biological functions. Interestingly among the newly identified sRNA candidates are antisense RNAs (asRNAs) associated to the housekeeping genes purA, fumC and pgi and potentially their regulation, emphasizing the significance of sRNAs for metabolic adaptation in L. monocytogenes.

  • Evolvability of feed-forward loop architecture biases its abundance in transcription networks.

    Widder S, Solé R, Macía J
    2012 - BMC Syst Biol, 7


    Transcription networks define the core of the regulatory machinery of cellular life and are largely responsible for information processing and decision making. At the small scale, interaction motifs have been characterized based on their abundance and some seemingly general patterns have been described. In particular, the abundance of different feed-forward loop motifs in gene regulatory networks displays systematic biases towards some particular topologies, which are much more common than others. The causative process of this pattern is still matter of debate.<br>We analyzed the entire motif-function landscape of the feed-forward loop using the formalism developed in a previous work. We evaluated the probabilities to implement possible functions for each motif and found that the kurtosis of these distributions correlate well with the natural abundance pattern. Kurtosis is a standard measure for the peakedness of probability distributions. Furthermore, we examined the functional robustness of the motifs facing mutational pressure in silico and observed that the abundance pattern is biased by the degree of their evolvability.<br>The natural abundance pattern of the feed-forward loop can be reconstructed concerning its intrinsic plasticity. Intrinsic plasticity is associated to each motif in terms of its capacity of implementing a repertoire of possible functions and it is directly linked to the motif's evolvability. Since evolvability is defined as the potential phenotypic variation of the motif upon mutation, the link plausibly explains the abundance pattern.

Book chapters and other publications

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