20,417 research outputs found
Self-Replicating Machines in Continuous Space with Virtual Physics
JohnnyVon is an implementation of self-replicating machines in
continuous two-dimensional space. Two types of particles drift
about in a virtual liquid. The particles are automata with
discrete internal states but continuous external relationships.
Their internal states are governed by finite state machines but
their external relationships are governed by a simulated physics
that includes Brownian motion, viscosity, and spring-like attractive
and repulsive forces. The particles can be assembled into patterns
that can encode arbitrary strings of bits. We demonstrate that, if
an arbitrary "seed" pattern is put in a "soup" of separate individual
particles, the pattern will replicate by assembling the individual
particles into copies of itself. We also show that, given sufficient
time, a soup of separate individual particles will eventually
spontaneously form self-replicating patterns. We discuss the implications
of JohnnyVon for research in nanotechnology, theoretical biology, and
artificial life
Semiconservative quasispecies equations for polysomic genomes: The general case
This paper develops a formulation of the quasispecies equations appropriate
for polysomic, semiconservatively replicating genomes. This paper is an
extension of previous work on the subject, which considered the case of haploid
genomes. Here, we develop a more general formulation of the quasispecies
equations that is applicable to diploid and even polyploid genomes.
Interestingly, with an appropriate classification of population fractions, we
obtain a system of equations that is formally identical to the haploid case. As
with the work for haploid genomes, we consider both random and immortal DNA
strand chromosome segregation mechanisms. However, in contrast to the haploid
case, we have found that an analytical solution for the mean fitness is
considerably more difficult to obtain for the polyploid case. Accordingly,
whereas for the haploid case we obtained expressions for the mean fitness for
the case of an analogue of the single-fitness-peak landscape for arbitrary
lesion repair probabilities (thereby allowing for non-complementary genomes),
here we solve for the mean fitness for the restricted case of perfect lesion
repair.Comment: 16 pages, 3 figure
On the Growth Rate of Non-Enzymatic Molecular Replicators
It is well known that non-enzymatic template directed molecular replicators X
+ nO ---> 2X exhibit parabolic growth d[X]/dt = k [X]^{1/2}. Here, we analyze
the dependence of the effective replication rate constant k on hybridization
energies, temperature, strand length, and sequence composition. First we derive
analytical criteria for the replication rate k based on simple thermodynamic
arguments. Second we present a Brownian dynamics model for oligonucleotides
that allows us to simulate their diffusion and hybridization behavior. The
simulation is used to generate and analyze the effect of strand length,
temperature, and to some extent sequence composition, on the hybridization
rates and the resulting optimal overall rate constant k. Combining the two
approaches allows us to semi-analytically depict a fitness landscape for
template directed replicators. The results indicate a clear replication
advantage for longer strands at low temperatures.Comment: Submitted to: Entrop
JohnnyVon: Self-Replicating Automata in Continuous Two-Dimensional Space
JohnnyVon is an implementation of self-replicating automata in continuous two-dimensional space. Two types of particles drift about in a virtual liquid. The particles are automata with discrete internal states but continuous external relationships. Their internal states are governed by finite state machines but their external relationships are governed by a simulated physics that includes brownian motion, viscosity, and spring-like attractive and repulsive forces. The particles can be assembled into patterns that can encode arbitrary strings of bits. We demonstrate that, if an arbitrary “seed” pattern is put in a “soup” of separate individual particles, the pattern will replicate by assembling the individual particles into copies of itself. We also show that, given sufficient time, a soup of separate individual particles will eventually spontaneously form self-replicating patterns. We discuss the implications of JohnnyVon for research in nanotechnology, theoretical biology, and artificial life
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
The influence of horizontal gene transfer on the mean fitness of unicellular populations in static environments
This paper develops a mathematical model describing the influence that
conjugation-mediated Horizontal Gene Transfer (HGT) has on the
mutation-selection balance in an asexually reproducing population of
unicellular, prokaryotic organisms. It is assumed that mutation-selection
balance is reached in the presence of a fixed background concentration of
antibiotic, to which the population must become resistant in order to survive.
We analyze the behavior of the model in the limit of low and high
antibiotic-induced first-order death rate constants, and find that the highest
mean fitness is obtained at low rates of bacterial conjugation. As the rate of
conjugation crosses a threshold, the mean fitness decreases to a minimum, and
then rises asymptotically to a limiting value as the rate of conjugation
becomes infinitely large. However, this limiting value is smaller than the mean
fitness obtained in the limit of low conjugation rate. This dependence of the
mean fitness on the conjugation rate is fairly small for the parameter ranges
we have considered, and disappears as the first-order death rate constant due
to the presence of antibiotic approaches zero. For large values of the
antibiotic death rate constant, we have obtained an analytical solution for the
behavior of the mean fitness that agrees well with the results of simulations.
The results of this paper suggest that conjugation-mediated HGT has a slightly
deleterious effect on the mean fitness of a population at mutation-selection
balance. Therefore, we argue that HGT confers a selective advantage by allowing
for faster adaptation to a new or changing environment. The results of this
paper are consistent with the observation that HGT can be promoted by
environmental stresses on a population.Comment: 27 pages, 4 figure
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