1,414 research outputs found
The Effect of Mutators on Adaptability in Time-Varying Fitness Landscapes
This Letter studies the quasispecies dynamics of a population capable of
genetic repair evolving on a time-dependent fitness landscape. We develop a
model that considers an asexual population of single-stranded, conservatively
replicating genomes, whose only source of genetic variation is due to copying
errors during replication. We consider a time-dependent, single-fitness-peak
landscape where the master sequence changes by a single point mutation every
time . We are able to analytically solve for the evolutionary dynamics
of the population in the point-mutation limit. In particular, our model
provides an analytical expression for the fraction of mutators in the dynamic
fitness landscape that agrees well with results from stochastic simulations.Comment: 4 pages, 3 figure
Evolutionary dynamics of adult stem cells: Comparison of random and immortal strand segregation mechanisms
This paper develops a point-mutation model describing the evolutionary
dynamics of a population of adult stem cells. Such a model may prove useful for
quantitative studies of tissue aging and the emergence of cancer. We consider
two modes of chromosome segregation: (1) Random segregation, where the daughter
chromosomes of a given parent chromosome segregate randomly into the stem cell
and its differentiating sister cell. (2) ``Immortal DNA strand''
co-segregation, for which the stem cell retains the daughter chromosomes with
the oldest parent strands. Immortal strand co-segregation is a mechanism,
originally proposed by Cairns (J. Cairns, {\it Nature} {\bf 255}, 197 (1975)),
by which stem cells preserve the integrity of their genomes. For random
segregation, we develop an ordered strand pair formulation of the dynamics,
analogous to the ordered strand pair formalism developed for quasispecies
dynamics involving semiconservative replication with imperfect lesion repair
(in this context, lesion repair is taken to mean repair of postreplication
base-pair mismatches). Interestingly, a similar formulation is possible with
immortal strand co-segregation, despite the fact that this segregation
mechanism is age-dependent. From our model we are able to mathematically show
that, when lesion repair is imperfect, then immortal strand co-segregation
leads to better preservation of the stem cell lineage than random chromosome
segregation. Furthermore, our model allows us to estimate the optimal lesion
repair efficiency for preserving an adult stem cell population for a given
period of time. For human stem cells, we obtain that mispaired bases still
present after replication and cell division should be left untouched, to avoid
potentially fixing a mutation in both DNA strands.Comment: 9 pages, 3 figure
Irreversible thermodynamics of open chemical networks I: Emergent cycles and broken conservation laws
In this and a companion paper we outline a general framework for the
thermodynamic description of open chemical reaction networks, with special
regard to metabolic networks regulating cellular physiology and biochemical
functions. We first introduce closed networks "in a box", whose thermodynamics
is subjected to strict physical constraints: the mass-action law, elementarity
of processes, and detailed balance. We further digress on the role of solvents
and on the seemingly unacknowledged property of network independence of free
energy landscapes. We then open the system by assuming that the concentrations
of certain substrate species (the chemostats) are fixed, whether because
promptly regulated by the environment via contact with reservoirs, or because
nearly constant in a time window. As a result, the system is driven out of
equilibrium. A rich algebraic and topological structure ensues in the network
of internal species: Emergent irreversible cycles are associated to
nonvanishing affinities, whose symmetries are dictated by the breakage of
conservation laws. These central results are resumed in the relation between the number of fundamental affinities , that of broken
conservation laws and the number of chemostats . We decompose the
steady state entropy production rate in terms of fundamental fluxes and
affinities in the spirit of Schnakenberg's theory of network thermodynamics,
paving the way for the forthcoming treatment of the linear regime, of
efficiency and tight coupling, of free energy transduction and of thermodynamic
constraints for network reconstruction.Comment: 18 page
THE RESOURCE NEXUS Preface and introduction to the Routledge Handbook
Demand for natural resources has grown rapidly for decades, and is expected to continue growing. These trends lead to repercussions, risks, and threats for humans and ecosystems at different scales. The challenges of sustainable resource management and governance are on numerous agendas, ranging from the G7 and G20 summits to UNEPâs International Resource Panel, World Economic Forum, SDG implementation, and a growing community of international scholars. Research highlights the importance of accounting for the interdependencies of resource use and sustainability goals such as eliminating hunger, mitigating climate change, and expanding energy access. There is a need to understand interdependencies and the feasibility of more integrated approaches. Debate is often framed in terms of a ânexusâ between water, energy, and food (sometimes including other resources). The main aim of this handbook is to come to grips with what the nexus is about, provide a reference textbook with an overview, and a survey on emerging and cutting-edge research, and application of the concept. This handbook is edited by five dedicated scholars, drawing on different schools of thought from different continents. Assembling a wide group of more than 50 authors across a host of disciplines and interdisciplinary fields, this volume rests on a thorough review of relevant literature and, in emerging with a distinct and original perspective, it conceptualizes the resource nexus as a heuristic for understanding critical interlinkages between uses of different natural resources for systems of provision such as water, energy, and food. The editors organized a symposium which took place in London in March 2015, debating various aspects of the resource nexus and refining the concept and defining the structure of the handbook. All chapters have been reviewed several times
Single-cell copy number variation detection
Detection of chromosomal aberrations from a single cell by array comparative genomic hybridization (single-cell array CGH), instead of from a population of cells, is an emerging technique. However, such detection is challenging because of the genome artifacts and the DNA amplification process inherent to the single cell approach. Current normalization algorithms result in inaccurate aberration detection for single-cell data. We propose a normalization method based on channel, genome composition and recurrent genome artifact corrections. We demonstrate that the proposed channel clone normalization significantly improves the copy number variation detection in both simulated and real single-cell array CGH data
Somatic Genomic Variations in Early Human Prenatal Development
Only 25 to 30% of conceptions result in a live birth. There is mounting evidence that the cause for this low fecundity is an extremely high incidence of chromosomal rearrangements occurring in the cleavage stage embryo. In this review, we gather all recent evidence for an extraordinary degree of mosaicisms in early embryogenesis. The presence of the rearrangements seen in the cleavage stage embryos can explain the origins of the placental mosaicisms seen during chorion villi sampling as well as the chromosomal anomalies seen in early miscarriages. Whereas these rearrangements often lead to implantation failure and early miscarriages, natural selection of the fittest cells in the embryo is the likely mechanism leading to healthy fetuses
DNA-interacting characteristics of the archaeal rudiviral protein SIRV2_Gp1
This is the final version of the article. Available from the publisher via the DOI in this record.Whereas the infection cycles of many bacterial and eukaryotic viruses have been
characterized in detail, those of archaeal viruses remain largely unexplored. Recently, studies on
a few model archaeal viruses such as SIRV2 (Sulfolobus islandicus rod-shaped virus) have revealed
an unusual lysis mechanism that involves the formation of pyramidal egress structures on the host
cell surface. To expand understanding of the infection cycle of SIRV2, we aimed to functionally
characterize gp1, which is a SIRV2 gene with unknown function. The SIRV2_Gp1 protein is highly
expressed during early stages of infection and it is the only protein that is encoded twice on the
viral genome. It harbours a helix-turn-helix motif and was therefore hypothesized to bind DNA.
The DNA-binding behavior of SIRV2_Gp1 was characterized with electrophoretic mobility shift
assays and atomic force microscopy. We provide evidence that the protein interacts with DNA and
that it forms large aggregates, thereby causing extreme condensation of the DNA. Furthermore, the
N-terminal domain of the protein mediates toxicity to the viral host Sulfolobus. Our findings may
lead to biotechnological applications, such as the development of a toxic peptide for the containment
of pathogenic bacteria, and add to our understanding of the Rudiviral infection cycle.This research was supported by the Geconcerteerde Onderzoeks Actie grant
âPhage Biosystemsâ from the KULeuven (http://www.kuleuven.be/onderzoek/kernprojecten/goa.htm). T.E.F.Q.
was supported by a FWO Pegasus Marie-Curie fellowship and a Marie-Curie Intra-European Fellowship.
The Belgian Federal Science Policy Office (Belspo) and the European Space Agency (ESA) PRODEX program
supported the work of RGW. E.P. was supported by start-up funds provided by the Vrije Universiteit Brussel (VUB)
Ab initio study of alanine polypeptide chains twisting
We have investigated the potential energy surfaces for alanine chains
consisting of three and six amino acids. For these molecules we have calculated
potential energy surfaces as a function of the Ramachandran angles Phi and Psi,
which are widely used for the characterization of the polypeptide chains. These
particular degrees of freedom are essential for the characterization of
proteins folding process. Calculations have been carried out within ab initio
theoretical framework based on the density functional theory and accounting for
all the electrons in the system. We have determined stable conformations and
calculated the energy barriers for transitions between them. Using a
thermodynamic approach, we have estimated the times of characteristic
transitions between these conformations. The results of our calculations have
been compared with those obtained by other theoretical methods and with the
available experimental data extracted from the Protein Data Base. This
comparison demonstrates a reasonable correspondence of the most prominent
minima on the calculated potential energy surfaces to the experimentally
measured angles Phi and Psi for alanine chains appearing in native proteins. We
have also investigated the influence of the secondary structure of polypeptide
chains on the formation of the potential energy landscape. This analysis has
been performed for the sheet and the helix conformations of chains of six amino
acids.Comment: 24 pages, 10 figure
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