39 research outputs found
The Error and Repair Catastrophes: A Two-Dimensional Phase Diagram in the Quasispecies Model
This paper develops a two gene, single fitness peak model for determining the
equilibrium distribution of genotypes in a unicellular population which is
capable of genetic damage repair. The first gene, denoted by ,
yields a viable organism with first order growth rate constant if it
is equal to some target ``master'' sequence . The second
gene, denoted by , yields an organism capable of genetic repair
if it is equal to some target ``master'' sequence . This
model is analytically solvable in the limit of infinite sequence length, and
gives an equilibrium distribution which depends on \mu \equiv L\eps , the
product of sequence length and per base pair replication error probability, and
\eps_r , the probability of repair failure per base pair. The equilibrium
distribution is shown to exist in one of three possible ``phases.'' In the
first phase, the population is localized about the viability and repairing
master sequences. As \eps_r exceeds the fraction of deleterious mutations,
the population undergoes a ``repair'' catastrophe, in which the equilibrium
distribution is still localized about the viability master sequence, but is
spread ergodically over the sequence subspace defined by the repair gene. Below
the repair catastrophe, the distribution undergoes the error catastrophe when exceeds \ln k/\eps_r , while above the repair catastrophe, the
distribution undergoes the error catastrophe when exceeds , where denotes the fraction of deleterious mutations.Comment: 14 pages, 3 figures. Submitted to Physical Review
The Genetic coding style of digital organisms
Recently, all the human genes were identified. But understanding the functions coded in the genes is of course a much harder problem. We are used to view DNA as some sort of a computer code, but there are striking differences. For example, by using entropy, it has been shown that the DNA code is much closer to random code than written text, which in turn is less ordered than ordinary computer code. Instead of saying that the DNA is badly written, using common programming standards, we might say that it is written in a different style − an evolutionary style. In this paper the coding style of creatures from the artificial life platform Avida has been studied. Avida creatures that have evolved under different size merit methods and mutation rates have been analysed using the notion of stylistic measures. The analysis has shown that the evolutionary coding style depends on the environment in which the code evolved, and that the choice of size merit method and mutation probabilities affect different stylistic properties of the genome. A better understanding of Avidas coding style, might eventually lead to insights of evolutionary codes in general
Solution of the Quasispecies Model for an Arbitrary Gene Network
In this paper, we study the equilibrium behavior of Eigen's quasispecies
equations for an arbitrary gene network. We consider a genome consisting of genes, so that each gene sequence may be written as . We assume a single fitness peak (SFP) model
for each gene, so that gene has some ``master'' sequence for which it is functioning. The fitness landscape is then determined by
which genes in the genome are functioning, and which are not. The equilibrium
behavior of this model may be solved in the limit of infinite sequence length.
The central result is that, instead of a single error catastrophe, the model
exhibits a series of localization to delocalization transitions, which we term
an ``error cascade.'' As the mutation rate is increased, the selective
advantage for maintaining functional copies of certain genes in the network
disappears, and the population distribution delocalizes over the corresponding
sequence spaces. The network goes through a series of such transitions, as more
and more genes become inactivated, until eventually delocalization occurs over
the entire genome space, resulting in a final error catastrophe. This model
provides a criterion for determining the conditions under which certain genes
in a genome will lose functionality due to genetic drift. It also provides
insight into the response of gene networks to mutagens. In particular, it
suggests an approach for determining the relative importance of various genes
to the fitness of an organism, in a more accurate manner than the standard
``deletion set'' method. The results in this paper also have implications for
mutational robustness and what C.O. Wilke termed ``survival of the flattest.''Comment: 29 pages, 5 figures, to be submitted to Physical Review
Does the Red Queen reign in the kingdom of digital organisms?
In competition experiments between two RNA viruses of equal or almost equal
fitness, often both strains gain in fitness before one eventually excludes the
other. This observation has been linked to the Red Queen effect, which
describes a situation in which organisms have to constantly adapt just to keep
their status quo. I carried out experiments with digital organisms
(self-replicating computer programs) in order to clarify how the competing
strains' location in fitness space influences the Red-Queen effect. I found
that gains in fitness during competition were prevalent for organisms that were
taken from the base of a fitness peak, but absent or rare for organisms that
were taken from the top of a peak or from a considerable distance away from the
nearest peak. In the latter two cases, either neutral drift and loss of the
fittest mutants or the waiting time to the first beneficial mutation were more
important factors. Moreover, I found that the Red-Queen dynamic in general led
to faster exclusion than the other two mechanisms.Comment: 10 pages, 5 eps figure
Eigen model as a quantum spin chain: exact dynamics
We map Eigen model of biological evolution [Naturwissenschaften {\bf 58}, 465
(1971)] into a one-dimensional quantum spin model with non-Hermitean
Hamiltonian. Based on such a connection, we derive exact relaxation periods for
the Eigen model to approach static energy landscape from various initial
conditions. We also study a simple case of dynamic fitness function.Comment: 10 pages. Physical Revew E vol. 69, in press (2004
On the Neutrality of Flowshop Scheduling Fitness Landscapes
Solving efficiently complex problems using metaheuristics, and in particular
local searches, requires incorporating knowledge about the problem to solve. In
this paper, the permutation flowshop problem is studied. It is well known that
in such problems, several solutions may have the same fitness value. As this
neutrality property is an important one, it should be taken into account during
the design of optimization methods. Then in the context of the permutation
flowshop, a deep landscape analysis focused on the neutrality property is
driven and propositions on the way to use this neutrality to guide efficiently
the search are given.Comment: Learning and Intelligent OptimizatioN Conference (LION 5), Rome :
Italy (2011
Survival-extinction phase transition in a bit-string population with mutation
A bit-string model for the evolution of a population of haploid organisms,
subject to competition, reproduction with mutation and selection is studied,
using mean field theory and Monte Carlo simulations. We show that, depending on
environmental flexibility and genetic variability, the model exhibits a phase
transtion between extinction and survival. The mean-field theory describes the
infinite-size limit, while simulations are used to study quasi-stationary
properties.Comment: 11 pages, 5 figure
V I R O L O G Y More than efficacy revealed by single-cell analysis of antiviral therapeutics
Because many aspects of viral infection dynamics and inhibition are governed by stochastic processes, single-cell analysis should provide more information than approaches using population averaging. We have developed a microfluidic device composed of ~6000 wells, with each well containing a microstructure to capture single, infected cells replicating an enterovirus expressing a fluorescent reporter protein. We have used this system to characterize enterovirus inhibitors with distinct mechanisms of action. Single-cell analysis reveals that each class of inhibitor interferes with the viral infection cycle in a manner that can be distinguished by principal component analysis. Single-cell analysis of antiviral candidates not only reveals efficacy but also facilitates clustering of drugs with the same mechanism of action and provides some indication of the ease with which resistance will develop
Single-Cell Virology: On-Chip Investigation of Viral Infection Dynamics
We have developed a high-throughput, microfluidics-based platform to perform kinetic analysis of viral infections in individual cells. We have analyzed thousands of individual poliovirus infections while varying experimental parameters, including multiplicity of infection, cell cycle, viral genotype, and presence of a drug. We make several unexpected observations masked by population-based experiments: (1) viral and cellular factors contribute uniquely and independently to viral infection kinetics; (2) cellular factors cause wide variation in replication start times; and (3) infections frequently begin later and replication occurs faster than predicted by population measurements. We show that mutational load impairs interaction of the viral population with the host, delaying replication start times and explaining the attenuated phenotype of a mutator virus. We show that an antiviral drug can selectively extinguish the most-fit members of the viral population. Single-cell virology facilitates discovery and characterization of virulence determinants and elucidation of mechanisms of drug action eluded by population methods. Guo et al. use a microfluidics device installed on a fluorescence microscope to monitor the kinetics of viral infection in single cells. Between-cell variation in outcomes of infection exists at all phases of the life cycle. Cellular gene expression governs the eclipse phase; viral genetics govern replication rate and yield
Predicting evolution and visualizing high-dimensional fitness landscapes
The tempo and mode of an adaptive process is strongly determined by the
structure of the fitness landscape that underlies it. In order to be able to
predict evolutionary outcomes (even on the short term), we must know more about
the nature of realistic fitness landscapes than we do today. For example, in
order to know whether evolution is predominantly taking paths that move upwards
in fitness and along neutral ridges, or else entails a significant number of
valley crossings, we need to be able to visualize these landscapes: we must
determine whether there are peaks in the landscape, where these peaks are
located with respect to one another, and whether evolutionary paths can connect
them. This is a difficult task because genetic fitness landscapes (as opposed
to those based on traits) are high-dimensional, and tools for visualizing such
landscapes are lacking. In this contribution, we focus on the predictability of
evolution on rugged genetic fitness landscapes, and determine that peaks in
such landscapes are highly clustered: high peaks are predominantly close to
other high peaks. As a consequence, the valleys separating such peaks are
shallow and narrow, such that evolutionary trajectories towards the highest
peak in the landscape can be achieved via a series of valley crossingsComment: 12 pages, 7 figures. To appear in "Recent Advances in the Theory and
Application of Fitness Landscapes" (A. Engelbrecht and H. Richter, eds.).
Springer Series in Emergence, Complexity, and Computation, 201