1,707 research outputs found
Equilibrium Distribution of Mutators in the Single Fitness Peak Model
This paper develops an analytically tractable model for determining the
equilibrium distribution of mismatch repair deficient strains in unicellular
populations. The approach is based on the single fitness peak (SFP) model,
which has been used in Eigen's quasispecies equations in order to understand
various aspects of evolutionary dynamics. As with the quasispecies model, our
model for mutator-nonmutator equilibrium undergoes a phase transition in the
limit of infinite sequence length. This "repair catastrophe" occurs at a
critical repair error probability of , where denotes the length of the genome controlling viability, while
denotes the overall length of the genome. The repair catastrophe therefore
occurs when the repair error probability exceeds the fraction of deleterious
mutations. Our model also gives a quantitative estimate for the equilibrium
fraction of mutators in {\it Escherichia coli}.Comment: 4 pages, 2 figures (included as separate PS files
Host-Parasite Co-evolution and Optimal Mutation Rates for Semi-conservative Quasispecies
In this paper, we extend a model of host-parasite co-evolution to incorporate
the semi-conservative nature of DNA replication for both the host and the
parasite. We find that the optimal mutation rate for the semi-conservative and
conservative hosts converge for realistic genome lengths, thus maintaining the
admirable agreement between theory and experiment found previously for the
conservative model and justifying the conservative approximation in some cases.
We demonstrate that, while the optimal mutation rate for a conservative and
semi-conservative parasite interacting with a given immune system is similar to
that of a conservative parasite, the properties away from this optimum differ
significantly. We suspect that this difference, coupled with the requirement
that a parasite optimize survival in a range of viable hosts, may help explain
why semi-conservative viruses are known to have significantly lower mutation
rates than their conservative counterparts
A Selective Advantage for Conservative Viruses
In this letter we study the full semi-conservative treatment of a model for
the co-evolution of a virus and an adaptive immune system. Regions of viability
are calculated for both conservatively and semi-conservatively replicating
viruses interacting with a realistic semi-conservatively replicating immune
system. The conservative virus is found to have a selective advantage in the
form of an ability to survive in regions with a wider range of mutation rates
than its semi-conservative counterpart. This may help explain the existence of
a rich range of viruses with conservatively replicating genomes, a trait which
is found nowhere else in nature.Comment: 4 pages, 2 figure
The Importance of DNA Repair in Tumor Suppression
The transition from a normal to cancerous cell requires a number of highly
specific mutations that affect cell cycle regulation, apoptosis,
differentiation, and many other cell functions. One hallmark of cancerous
genomes is genomic instability, with mutation rates far greater than those of
normal cells. In microsatellite instability (MIN tumors), these are often
caused by damage to mismatch repair genes, allowing further mutation of the
genome and tumor progression. These mutation rates may lie near the error
catastrophe found in the quasispecies model of adaptive RNA genomes, suggesting
that further increasing mutation rates will destroy cancerous genomes. However,
recent results have demonstrated that DNA genomes exhibit an error threshold at
mutation rates far lower than their conservative counterparts. Furthermore,
while the maximum viable mutation rate in conservative systems increases
indefinitely with increasing master sequence fitness, the semiconservative
threshold plateaus at a relatively low value. This implies a paradox, wherein
inaccessible mutation rates are found in viable tumor cells. In this paper, we
address this paradox, demonstrating an isomorphism between the conservatively
replicating (RNA) quasispecies model and the semiconservative (DNA) model with
post-methylation DNA repair mechanisms impaired. Thus, as DNA repair becomes
inactivated, the maximum viable mutation rate increases smoothly to that of a
conservatively replicating system on a transformed landscape, with an upper
bound that is dependent on replication rates. We postulate that inactivation of
post-methylation repair mechanisms are fundamental to the progression of a
tumor cell and hence these mechanisms act as a method for prevention and
destruction of cancerous genomes.Comment: 7 pages, 5 figures; Approximation replaced with exact calculation;
Minor error corrected; Minor changes to model syste
Proposed criteria for the evaluation of the scientific quality of mandatory rat and mouse feeding trials with whole food/feed derived from genetically modified plants
In recent years, animal feeding trials conducted with whole food/feed have been a focal issue in the controversy on the safety assessment of genetically modified (GM) plants and derived food/feed. Within the scientific community and among stakeholders, quite different views have been expressed on how these studies should be conducted, analysed and interpreted, what they might add in terms of information relevant to safety and whether 90-day rodent feeding trials should be mandatory. Despite the fact that the Commission Implementing Regulation (EU) No. 503/2013 (specifying the requirements for the risk assessment of GM food/feed) requests mandatory 90-day feeding trials for GM plants with single transformation events, the controversy continues. This is due to the fact that in 2016 the European Commission will have to review this particular provision in the legislation (ibid, Article 12), and because of questions raised by long-term feeding studies with GM maize
Modeling the interactions of biomatter and biofluid
The internal motions of biomatter immersed in biofluid are investigated. The
interactions between the fragments of biomatter and its surrounding biofluid
are modeled using field theory. In the model, the biomatter is coupled to the
gauge field representing the biofluid. It is shown that at non-relativistic
limit various equation of motions, from the well-known Sine-Gordon equation to
the simultaneous nonlinear equations, can be reproduced within a single
framework.Comment: 10 pages, 3 figure
Computational models for inferring biochemical networks
Biochemical networks are of great practical importance. The interaction of biological compounds in cells has been enforced to a proper understanding by the numerous bioinformatics projects, which contributed to a vast amount of biological information. The construction of biochemical systems (systems of chemical reactions), which include both topology and kinetic constants of the chemical reactions, is NP-hard and is a well-studied system biology problem. In this paper, we propose a hybrid architecture, which combines genetic programming and simulated annealing in order to generate and optimize both the topology (the network) and the reaction rates of a biochemical system. Simulations and analysis of an artificial model and three real models (two models and the noisy version of one of them) show promising results for the proposed method.The Romanian National Authority for Scientific Research, CNDI–UEFISCDI,
Project No. PN-II-PT-PCCA-2011-3.2-0917
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