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Grilli J.,University of Milan | Bassetti B.,University of Milan | Bassetti B.,National Institute of Nuclear Physics, Italy | Maslov S.,Brookhaven National Laboratory | And 2 more authors.
Nucleic Acids Research | Year: 2012

We propose and study a class-expansioninnovationloss model of genome evolution taking into account biological roles of genes and their constituent domains. In our model, numbers of genes in different functional categories are coupled to each other. For example, an increase in the number of metabolic enzymes in a genome is usually accompanied by addition of new transcription factors regulating these enzymes. Such coupling can be thought of as a proportional 'recipe' for genome composition of the type 'a spoonful of sugar for each egg yolk'. The model jointly reproduces two known empirical laws: the distribution of family sizes and the non-linear scaling of the number of genes in certain functional categories (e.g. transcription factors) with genome size. In addition, it allows us to derive a novel relation between the exponents characterizing these two scaling laws, establishing a direct quantitative connection between evolutionary and functional categories. It predicts that functional categories that grow faster-than-linearly with genome size to be characterized by flatter-than-average family size distributions. This relation is confirmed by our bioinformatics analysis of prokaryotic genomes. This proves that the joint quantitative trends of functional and evolutionary classes can be understood in terms of evolutionary growth with proportional recipes. © The Author(s) 2011. Published by Oxford University Press.


Muller P.,University Paris - Sud | Bouly J.-P.,CNRS Laboratory of Computational and Quantitative Biology
FEBS Letters | Year: 2015

Even though the plant photoreceptors cryptochromes were discovered more than 20 years ago, the mechanism through which they transduce light signals to their partner molecules such as COP1 (Constitutive Photomorphogenic 1) or SPA1 (Suppressor of Phytochrome A) still remains to be established. We propose that a negative charge induced by light in the vicinity of the flavin chromophore initiates cryptochrome 1 signalling. This negative charge might expel the protein-bound ATP from the binding pocket, thereby pushing off the C-terminus that covers the ATP pocket in the dark state of the protein. This conformational change should allow for phosphorylation of previously inaccessible amino acids. A partially phosphorylated 'ESSSSGRR-VPE' fragment of the C-terminus could mimic the sequence of the transcription factor HY5 that is essential for binding to the negative regulator of photomorphogenesis COP1. HY5 release through competition for the COP1 binding site could represent the long-sought connection between light activation of cryptochrome and modulation of photomorphogenesis. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Javer A.,University of Cambridge | Kuwada N.J.,University of Washington | Long Z.,University of Minnesota | Benza V.G.,University of Insubria | And 5 more authors.
Nature Communications | Year: 2014

The physical nature of the bacterial chromosome has important implications for its function. Using high-resolution dynamic tracking, we observe the existence of rare but ubiquitous 'rapid movements' of chromosomal loci exhibiting near-ballistic dynamics. This suggests that these movements are either driven by an active machinery or part of stress-relaxation mechanisms. Comparison with a null physical model for subdiffusive chromosomal dynamics shows that rapid movements are excursions from a basal subdiffusive dynamics, likely due to driven and/or stress-relaxation motion. Additionally, rapid movements are in some cases coupled with known transitions of chromosomal segregation. They do not co-occur strictly with replication, their frequency varies with growth condition and chromosomal coordinate, and they show a preference for longitudinal motion. These findings support an emerging picture of the bacterial chromosome as off-equilibrium active matter and help developing a correct physical model of its in vivo dynamic structure. © 2014 Macmillan Publishers Limited. All rights reserved.


Bruot N.,University of Cambridge | Damet L.,University of Cambridge | Kotar J.,University of Cambridge | Cicuta P.,University of Cambridge | And 2 more authors.
Physical Review Letters | Year: 2011

A two-state oscillator in a viscous liquid is composed of a micron-scale particle whose intrinsic dynamics is defined by linear potentials that undergo configuration-coupled transitions and is externally driven by a piecewise constant periodic force of varying amplitude and frequency. This elementary example of "active matter" has the minimal elements that allow us to study synchronization in the presence of thermal fluctuations. Experiments reveal the presence of synchronized states (and Arnol'd tongues), which we explain using analytical and numerical calculations. The system maintains synchronization by adjusting the phase between the bead and the clock. We discuss the relevance of this model to synchronization in real-world systems, including the role of thermal noise. © 2011 American Physical Society.


Benza V.G.,University of Insubria | Bassetti B.,University of Milan | Dorfman K.D.,University of Minnesota | Scolari V.F.,CNRS Laboratory of Computational and Quantitative Biology | And 6 more authors.
Reports on Progress in Physics | Year: 2012

Recent experimental and theoretical approaches have attempted to quantify the physical organization (compaction and geometry) of the bacterial chromosome with its complement of proteins (the nucleoid). The genomic DNA exists in a complex and dynamic protein-rich state, which is highly organized at various length scales. This has implications for modulating (when not directly enabling) the core biological processes of replication, transcription and segregation. We overview the progress in this area, driven in the last few years by new scientific ideas and new interdisciplinary experimental techniques, ranging from high space- and time-resolution microscopy to high-throughput genomics employing sequencing to map different aspects of the nucleoid-related interactome. The aim of this review is to present the wide spectrum of experimental and theoretical findings coherently, from a physics viewpoint. In particular, we highlight the role that statistical and soft condensed matter physics play in describing this system of fundamental biological importance, specifically reviewing classic and more modern tools from the theory of polymers. We also discuss some attempts toward unifying interpretations of the current results, pointing to possible directions for future investigation. © 2012 IOP Publishing Ltd.


Bruot N.,University of Cambridge | Kotar J.,University of Cambridge | De Lillo F.,University of Turin | De Lillo F.,University of Genoa | And 4 more authors.
Physical Review Letters | Year: 2012

Motile cilia are highly conserved structures in the evolution of organisms, generating the transport of fluid by periodic beating, through remarkably organized behavior in space and time. It is not known how these spatiotemporal patterns emerge and what sets their properties. Individual cilia are nonequilibrium systems with many degrees of freedom. However, their description can be represented by simpler effective force laws that drive oscillations, and paralleled with nonlinear phase oscillators studied in physics. Here a synthetic model of two phase oscillators, where colloidal particles are driven by optical traps, proves the role of the average force profile in establishing the type and strength of synchronization. We find that highly curved potentials are required for synchronization in the presence of noise. The applicability of this approach to biological data is also illustrated by successfully mapping the behavior of cilia in the alga Chlamydomonas onto the coarse-grained model. © 2012 American Physical Society.


Chen G.,Stowers Institute for Medical Research | Chen G.,University of Kansas Medical Center | Mulla W.A.,Stowers Institute for Medical Research | Mulla W.A.,University of Kansas Medical Center | And 13 more authors.
Cell | Year: 2015

Aneuploid genomes, characterized by unbalanced chromosome stoichiometry (karyotype), are associated with cancer malignancy and drug resistance of pathogenic fungi. The phenotypic diversity resulting from karyotypic diversity endows the cell population with superior adaptability. We show here, using a combination of experimental data and a general stochastic model, that the degree of phenotypic variation, thus evolvability, escalates with the degree of overall growth suppression. Such scaling likely explains the challenge of treating aneuploidy diseases with a single stress-inducing agent. Instead, we propose the design of an "evolutionary trap" (ET) targeting both karyotypic diversity and fitness. This strategy entails a selective condition "channeling" a karyotypically divergent population into one with a predominant and predictably drugable karyotypic feature. We provide a proof-of-principle case in budding yeast and demonstrate the potential efficacy of this strategy toward aneuploidy-based azole resistance in Candida albicans. By analyzing existing pharmacogenomics data, we propose the potential design of an ET against glioblastoma. © 2015 Elsevier Inc.


Javer A.,University of Cambridge | Long Z.,University of Minnesota | Nugent E.,University of Cambridge | Grisi M.,University of Cambridge | And 7 more authors.
Nature Communications | Year: 2013

In bacteria, chromosomal architecture shows strong spatial and temporal organization, and regulates key cellular functions, such as transcription. Tracking the motion of chromosomal loci at short timescales provides information related to both the physical state of the nucleo-protein complex and its local environment, independent of large-scale motions related to genome segregation. Here we investigate the short-time (0.1-10 s) dynamics of fluorescently labelled chromosomal loci in Escherichia coli at different growth rates. At these timescales, we observe for the first time a dependence of the loci's apparent diffusion on both their subcellular localization and chromosomal coordinate, and we provide evidence that the properties of the chromosome are similar in the tested growth conditions. Our results indicate that either non-equilibrium fluctuations due to enzyme activity or the organization of the genome as a polymer-protein complex vary as a function of the distance from the origin of replication. © 2013 Macmillan Publishers Limited. All rights reserved.


Rotondo P.,University of Milan | Cosentino Lagomarsino M.,CNRS Laboratory of Computational and Quantitative Biology | Viola G.,Chalmers University of Technology | Viola G.,RWTH Aachen
Physical Review Letters | Year: 2015

Using an approach inspired from spin glasses, we show that the multimode disordered Dicke model is equivalent to a quantum Hopfield network. We propose variational ground states for the system at zero temperature, which we conjecture to be exact in the thermodynamic limit. These ground states contain the information on the disordered qubit-photon couplings. These results lead to two intriguing physical implications. First, once the qubit-photon couplings can be engineered, it should be possible to build scalable pattern-storing systems whose dynamics is governed by quantum laws. Second, we argue with an example of how such Dicke quantum simulators might be used as a solver of "hard" combinatorial optimization problems. © 2015 American Physical Society.


Arnone M.I.,Stazione Zoologica Anton Dohrn | Andrikou C.,University of Bergen | Annunziata R.,CNRS Laboratory of Computational and Quantitative Biology
Current Opinion in Genetics and Development | Year: 2016

One of the main challenges in Evolutionary Developmental Biology is to understand to which extent developmental changes are driven by regulatory alterations in the genomic sequence. In the recent years, the focus of comparative developmental studies has moved towards a systems biology approach providing a better understanding of the evolution of gene interactions that form the so called Gene Regulatory Networks (GRN). Echinoderms provide a powerful system to reveal regulatory mechanisms and within the past decade, due to the latest technological innovations, a great number of studies have provided valuable information for comparative GRN analyses. In this review we describe recent advances in evolution of GRNs arising from echinoderm systems, focusing on the properties of conserved regulatory kernels, circuit co-option events and GRN topological rearrangements. © 2016 Elsevier Ltd

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