4,339 research outputs found
Selective pressures on genomes in molecular evolution
We describe the evolution of macromolecules as an information transmission
process and apply tools from Shannon information theory to it. This allows us
to isolate three independent, competing selective pressures that we term
compression, transmission, and neutrality selection. The first two affect
genome length: the pressure to conserve resources by compressing the code, and
the pressure to acquire additional information that improves the channel,
increasing the rate of information transmission into each offspring. Noisy
transmission channels (replication with mutations) gives rise to a third
pressure that acts on the actual encoding of information; it maximizes the
fraction of mutations that are neutral with respect to the phenotype. This
neutrality selection has important implications for the evolution of
evolvability. We demonstrate each selective pressure in experiments with
digital organisms.Comment: 16 pages, 3 figures, to be published in J. theor. Biolog
Force steps during viral DNA packaging ?
Biophysicists and structural biologists increasingly acknowledge the role
played by the mechanical properties of macromolecules as a critical element in
many biological processes. This change has been brought about, in part, by the
advent of single molecule biophysics techniques that have made it possible to
exert piconewton forces on key macromolecules and observe their deformations at
nanometer length scales, as well as to observe the mechanical action of
macromolecules such as molecular motors. This has opened up immense
possibilities for a new generation of mechanical investigations that will
respond to such measurements in an attempt to develop a coherent theory for the
mechanical behavior of macromolecules under conditions where thermal and
chemical effects are on an equal footing with deterministic forces. This paper
presents an application of the principles of mechanics to the problem of DNA
packaging, one of the key events in the life cycle of bacterial viruses with
special reference to the nature of the internal forces that are built up during
the DNA packaging process.Comment: 18 pages, 7 figures, To appear in the Journal of Mechanics and
Physics of Solid
Portal protein functions akin to a DNA-sensor that couples genome-packaging to icosahedral capsid maturation.
Tailed bacteriophages and herpesviruses assemble infectious particles via an empty precursor capsid (or \u27procapsid\u27) built by multiple copies of coat and scaffolding protein and by one dodecameric portal protein. Genome packaging triggers rearrangement of the coat protein and release of scaffolding protein, resulting in dramatic procapsid lattice expansion. Here, we provide structural evidence that the portal protein of the bacteriophage P22 exists in two distinct dodecameric conformations: an asymmetric assembly in the procapsid (PC-portal) that is competent for high affinity binding to the large terminase packaging protein, and a symmetric ring in the mature virion (MV-portal) that has negligible affinity for the packaging motor. Modelling studies indicate the structure of PC-portal is incompatible with DNA coaxially spooled around the portal vertex, suggesting that newly packaged DNA triggers the switch from PC- to MV-conformation. Thus, we propose the signal for termination of \u27Headful Packaging\u27 is a DNA-dependent symmetrization of portal protein
Necrotizing meningoencephalitis in atypical dog breeds: a case series and literature review.
BackgroundCanine necrotizing meningoencephalitis (NME) is a fatal, noninfectious inflammatory disease of unknown etiology. NME has been reported only in a small number of dog breeds, which has led to the presumption that it is a breed-restricted disorder.Hypothesis/objectivesOur objective was to describe histopathologically confirmed NME in dog breeds in which the condition has not been reported previously and to provide preliminary evidence that NME affects a wider spectrum of dog breeds than previously reported.AnimalsFour dogs with NME.MethodsArchives from 3 institutions and from 1 author's (BS) collection were reviewed to identify histopathologically confirmed cases of NME in breeds in which the disease has not been reported previously. Age, sex, breed, survival from onset of clinical signs, and histopathologic findings were evaluated.ResultsNecrotizing meningoencephalitis was identified in 4 small dog breeds (Papillon, Shih Tzu, Coton de Tulear, and Brussels Griffon). Median age at clinical evaluation was 2.5 years. Histopathologic abnormalities included 2 or more of the following: lymphoplasmacytic or histiocytic meningoencephalitis or encephalitis, moderate-to-severe cerebrocortical necrosis, variable involvement of other anatomic locations within the brain (cerebellum, brainstem), and absence of detectable infectious agents.Conclusions and clinical importanceUntil now, NME has only been described in 5 small dog breeds. We document an additional 4 small breeds previously not shown to develop NME. Our cases further illustrate that NME is not a breed-restricted disorder and should be considered in the differential diagnosis for dogs with signalment and clinical signs consistent with inflammatory brain disease
Causality, Information and Biological Computation: An algorithmic software approach to life, disease and the immune system
Biology has taken strong steps towards becoming a computer science aiming at
reprogramming nature after the realisation that nature herself has reprogrammed
organisms by harnessing the power of natural selection and the digital
prescriptive nature of replicating DNA. Here we further unpack ideas related to
computability, algorithmic information theory and software engineering, in the
context of the extent to which biology can be (re)programmed, and with how we
may go about doing so in a more systematic way with all the tools and concepts
offered by theoretical computer science in a translation exercise from
computing to molecular biology and back. These concepts provide a means to a
hierarchical organization thereby blurring previously clear-cut lines between
concepts like matter and life, or between tumour types that are otherwise taken
as different and may not have however a different cause. This does not diminish
the properties of life or make its components and functions less interesting.
On the contrary, this approach makes for a more encompassing and integrated
view of nature, one that subsumes observer and observed within the same system,
and can generate new perspectives and tools with which to view complex diseases
like cancer, approaching them afresh from a software-engineering viewpoint that
casts evolution in the role of programmer, cells as computing machines, DNA and
genes as instructions and computer programs, viruses as hacking devices, the
immune system as a software debugging tool, and diseases as an
information-theoretic battlefield where all these forces deploy. We show how
information theory and algorithmic programming may explain fundamental
mechanisms of life and death.Comment: 30 pages, 8 figures. Invited chapter contribution to Information and
Causality: From Matter to Life. Sara I. Walker, Paul C.W. Davies and George
Ellis (eds.), Cambridge University Pres
- …