arXiv subjects

Michael W. Deem

Publications and source records attributed to Michael W. Deem.

At least 55 records · Page 3Linked to original sources

arXiv2009

Spontaneous Emergence of Modularity in a Model of Evolving Individuals and in Real Networks

We investigate the selective forces that promote the emergence of modularity in nature. We demonstrate the spontaneous emergence of modularity in a population of individuals that evolve in a changing environment. We show that the level of modularity correlates with the rapidity and severity of environmental change. The modularity arises as a synergistic response to the noise in the environment in the presence of horizontal gene transfer. We suggest that the hierarchical structure observed in the natural world may be a broken symmetry state, which generically results from evolution in a changing environment. To support our results, we analyze experimental protein interaction data and show that protein interaction networks became increasingly modular as evolution proceeded over the last four billion years. We also discuss a method to determine the divergence time of a protein.

q-bio.MN↗

arXiv2008

Quasispecies Theory for Horizontal Gene Transfer and Recombination

We introduce a generalization of the parallel, or Crow-Kimura, and Eigen models of molecular evolution to represent the exchange of genetic information between individuals in a population. We study the effect of different schemes of genetic recombination on the steady-state mean fitness and distribution of individuals in the population, through an analytic field theoretic mapping. We investigate both horizontal gene transfer from a population and recombination between pairs of individuals. Somewhat surprisingly, these nonlinear generalizations of quasi-species theory to modern biology are analytically solvable. For two-parent recombination, we find two selected phases, one of which is spectrally rigid. We present exact analytical formulas for the equilibrium mean fitness of the population, in terms of a maximum principle, which are generally applicable to any permutation invariant replication rate function. For smooth fitness landscapes, we show that when positive epistatic interactions are present, recombination or horizontal gene transfer introduces a mild load against selection. Conversely, if the fitness landscape exhibits negative epistasis, horizontal gene transfer or recombination introduce an advantage by enhancing selection towards the fittest genotypes. These results prove that the mutational deterministic hypothesis holds for quasi-species models. For the discontinuous single sharp peak fitness landscape, we show that horizontal gene transfer has no effect on the fitness, while recombination decreases the fitness, for both the parallel and the Eigen models. We present numerical and analytical results as well as phase diagrams for the different cases.

q-bio.PE↗

arXiv2007

Spontaneous Emergence of Modularity in a Model of Evolving Individuals

q-bio.PE↗

arXiv2006

Phase Diagrams of Quasispecies Theory with Recombination and Horizontal Gene Transfer

We consider how transfer of genetic information between individuals influences the phase diagram and mean fitness of both the Eigen and the parallel, or Crow-Kimura, models of evolution. In the absence of genetic transfer, these physical models of evolution consider the replication and point mutation of the genomes of independent individuals in a large population. A phase transition occurs, such that below a critical mutation rate an identifiable quasispecies forms. We generalize these models of quasispecies evolution to include horizontal gene transfer. We show how transfer of genetic information changes the phase diagram and mean fitness and introduces metastability in quasispecies theory, via an analytic field theoretic mapping.

q-bio.PE↗

arXiv2006

A Physical Theory of the Competition that Allows HIV to Escape from the Immune System

Competition within the immune system may degrade immune control of viral infections. We formalize the evolution that occurs in both HIV-1 and the immune system quasispecies. Inclusion of competition in the immune system leads to a novel balance between the immune response and HIV-1, in which the eventual outcome is HIV-1 escape rather than control. The analytical model reproduces the three stages of HIV-1 infection. We propose a vaccine regimen that may be able to reduce competition between T cells, potentially eliminating the third stage of HIV-1.

q-bio.PE↗

arXiv2006

Schwinger Boson Formulation and Solution of the Crow-Kimura and Eigen Models of Quasispecies Theory

We express the Crow-Kimura and Eigen models of quasispecies theory in a functional integral representation. We formulate the spin coherent state functional integrals using the Schwinger Boson method. In this formulation, we are able to deduce the long-time behavior of these models for arbitrary replication and degradation functions. We discuss the phase transitions that occur in these models as a function of mutation rate. We derive for these models the leading order corrections to the infinite genome length limit.

q-bio.PE↗

arXiv2005

Parallel Tempering: Theory, Applications, and New Perspectives

We review the history of the parallel tempering simulation method. From its origins in data analysis, the parallel tempering method has become a standard workhorse of physiochemical simulations. We discuss the theory behind the method and its various generalizations. We mention a selected set of the many applications that have become possible with the introduction of parallel tempering and we suggest several promising avenues for future research.

physics.comp-ph↗

arXiv2005

Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross-reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system a balance has evolved between binding affinity and specificity in the mechanism for searching the amino acid sequence space of antibodies.

q-bio.PE↗

arXiv2005

Quantifying Influenza Vaccine Efficacy and Antigenic Distance

We introduce a new measure of antigenic distance between influenza A vaccine and circulating strains. The measure correlates well with efficacies of the H3N2 influenza A component of the annual vaccine between 1971 and 2004, as do results of a theory of the immune response to influenza following vaccination. This new measure of antigenic distance is correlated with vaccine efficacy to a greater degree than are current state-of-the-art phylogenetic sequence analyzes or ferret antisera inhibition assays. We suggest that this new measure of antigenic distance be used in the design of the annual influenza vaccine and in the interpretation of vaccine efficacy monitoring.

q-bio.BM↗

arXiv2004

Markov Chains of Infinite Order and Asymptotic Satisfaction of Balance: Application to the Adaptive Integration Method

Adaptive Monte Carlo methods can be viewed as implementations of Markov chains with infinite memory. We derive a general condition for the convergence of a Monte Carlo method whose history dependence is contained within the simulated density distribution. In convergent cases, our result implies that the balance condition need only be satisfied asymptotically. As an example, we show that the adaptive integration method converges.

physics.comp-ph↗

arXiv2004

Length, Protein-Protein Interactions, and Complexity

The evolutionary reason for the increase in gene length from archaea to prokaryotes to eukaryotes observed in large scale genome sequencing efforts has been unclear. We propose here that the increasing complexity of protein-protein interactions has driven the selection of longer proteins, as longer proteins are more able to distinguish among a larger number of distinct interactions due to their greater average surface area. Annotated protein sequences available from the SWISS-PROT database were analyzed for thirteen eukaryotes, eight bacteria, and two archaea species. The number of subcellular locations to which each protein is associated is used as a measure of the number of interactions to which a protein participates. Two databases of yeast protein-protein interactions were used as another measure of the number of interactions to which each \emph{S. cerevisiae} protein participates. Protein length is shown to correlate with both number of subcellular locations to which a protein is associated and number of interactions as measured by yeast two-hybrid experiments. Protein length is also shown to correlate with the probability that the protein is encoded by an essential gene. Interestingly, average protein length and number of subcellular locations are not significantly different between all human proteins and protein targets of known, marketed drugs. Increased protein length appears to be a significant mechanism by which the increasing complexity of protein-protein interaction networks is accommodated within the natural evolution of species. Consideration of protein length may be a valuable tool in drug design, one that predicts different strategies for inhibiting interactions in aberrant and normal pathways.

q-bio.MN↗

arXiv2004

Epitope analysis for influenza vaccine design

Until now, design of the annual influenza vaccine has relied on phylogenetic or whole-sequence comparisons of the viral coat proteins hemagglutinin and neuraminidase, with vaccine effectiveness assumed to correlate monotonically to the vaccine-influenza sequence difference. We use a theory from statistical mechanics to quantify the non-monotonic immune response that results from antigenic drift in the epitopes of the hemagglutinin and neuraminidase proteins. The results explain the ineffectiveness of the 2003--2004 influenza vaccine in the United States and provide an accurate measure by which to optimize the effectiveness of future annual influenza vaccines.

q-bio.BM↗

arXiv2004

Evolvability is a Selectable Trait

Concomitant with the evolution of biological diversity must have been the evolution of mechanisms that facilitate evolution, due to the essentially infinite complexity of protein sequence space. We describe how evolvability can be an object of Darwinian selection, emphasizing the collective nature of the process. We quantify our theory with computer simulations of protein evolution. These simulations demonstrate that rapid or dramatic environmental change leads to selection for greater evolvability. The selective pressure for large scale genetic moves, such as DNA exchange, becomes increasingly strong as the environmental conditions become more uncertain. Our results demonstrate that evolvability is a selectable trait and allow for the explanation of a large body of experimental results.

q-bio.PE↗

arXiv2004

Modulation of Base Specific Mutation and Recombination Rates Enables Functional Adaptation within the Context of the Genetic Code

The persistence of life requires populations to adapt at a rate commensurate with the dynamics of their environment. Successful populations that inhabit highly variable environments have evolved mechanisms to increase the likelihood of successful adaptation. We introduce a $64 \times 64$ matrix to quantify base-specific mutation potential, analyzing four different replicative systems, error-prone PCR, mouse antibodies, a nematode, and Drosophila. Mutational tendencies are correlated with the structural evolution of proteins. In systems under strong selective pressure, mutational biases are shown to favor the adaptive search of space, either by base mutation or by recombination. Such adaptability is discussed within the context of the genetic code at the levels of replication and codon usage.

q-bio.GN↗

arXiv2004

Correlations in the T Cell Response to Altered Peptide Ligands

The vertebrate immune system is a wonder of modern evolution. Occasionally, however, correlations within the immune system lead to inappropriate recruitment of preexisting T cells against novel viral diseases. We present a random energy theory for the correlations in the naive and memory T cell immune responses. The non-linear susceptibility of the random energy model to structural changes captures the correlations in the immune response to mutated antigens. We show how the sequence-level diversity of the T cell repertoire drives the dynamics of the immune response against mutated viral antigens.

q-bio.BM↗

arXiv2004

Optimal Allocation of Replicas to Processors in Parallel Tempering Simulations

The optimal allocation of replicas to a homogeneous or heterogenous set of processors is derived for parallel tempering simulations on multi-processor machines. In the general case, it is possible without substantially increasing wall clock time to achieve nearly perfect utilization of CPU time. Random fluctuations in the execution times of each of the replicas do not significantly degrade the performance of the scheduler.

physics.comp-ph↗

arXiv2003

Complexity in the Immune System

The immune system is a real-time example of an evolving system that navigates the essentially infinite complexity of protein sequence space. How this system responds to disease and vaccination is discussed. Of particular focus is the case when vaccination leads to increased susceptibility to disease, a phenomenon termed original antigenic sin. A physical theory of protein evolution to explain limitations in the immune system response to vaccination and disease is discussed, and original antigenic sin is explained as stemming from localization of the immune system response in antibody sequence space. This localization is a result of the roughness in sequence space of the evolved antibody affinity constant for antigen and is observed for diseases with high year-to-year mutation rates, such as influenza.

q-bio.CB↗

arXiv2003

Two-Dimensional Diffusion in the Presence of Topological Disorder

How topological defects affect the dynamics of particles hopping between lattice sites of a distorted, two-dimensional crystal is addressed. Perturbation theory and numerical simulations show that weak, short-ranged topological disorder leads to a finite reduction of the diffusion coefficient. Renormalization group theory and numerical simulations suggest that longer-ranged disorder, such as that from randomly placed dislocations or random disclinations with no net disclinicity, leads to subdiffusion at long times.

cond-mat.stat-mech↗