Claus O. Wilke

Translationally Optimal Codons Associate with Structurally Sensitive Sites in Proteins (2009)

Zhou, Tong, Weems, Mason, Wilke, Claus O.

The mistranslation-induced protein misfolding hypothesis predicts that selection should prefer high-fidelity codons at sites at which translation errors are structurally disruptive and lead to...

84 R EPORTS Adaptive Radiation from Resource Competition in Digital Organisms (2008)

Stephanie S. Chow, Claus O. Wilke, Charles Ofria, Richard E. Lenski, Christoph Adami

Species richness often peaks at intermediate productivity and decreases as resources become more or less abundant. The mechanisms that produce this pattern are not completely known, but several...

Address: (2008)

Jesse D. Bloom, D. Allan Drummond, Frances H. Arnold, Claus O. Wilke

Structural determinants of the rate of protein evolution

The look-ahead effect of phenotypic mutations (2008)

Whitehead, Dion J, Wilke, Claus O, Vernazobres, David, Bornberg-Bauer, Erich

Abstract Background The evolution of complex molecular traits such as disulphide bridges often requires multiple mutations. The intermediate steps in such evolutionary trajectories are likely to be...

Dynamic fitness landscapes in molecular evolution (2008)

Claus O. Wilke, Christopher Ronnewinkel, Thomas Martinetz

We study self-replicating molecules under externally varying conditions. Changing conditions such as temperature variations and/or alterations in the environment’s resource composition lead to both...

Low-level HIV-1 replication and the dynamics of the resting CD4+T cell reservoir for HIV-1 in the setting of HAART (2008)

Sedaghat, Ahmad R, Siliciano, Robert F, Wilke, Claus O

Abstract Background In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard...

Dynamic tness landscapes: Expansions for small mutation rates (2007)

Tness Landscapes Expansions, Claus O. Wilke, Christopher Ronnewinkel

We study the evolution of asexual microorganisms with small mutation rate in uctuating environments, and develop techniques that allow us to expand the formal solution of the evolution equations to...

Dynamic Fitness Landscapes in Molecular (2007)

Evolution Claus Wilke, Claus O. Wilke, Christopher Ronnewinkel, Thomas Martinetz

We study self-replicating molecules under externally varying conditions. Changing conditions such as temperature variations and/or alterations in the environment's resource composition lead to...

The look-ahead effect of phenotypic mutations (2007)

Whitehead, Dion J., Wilke, Claus O., Vernazobres, David, Bornberg-Bauer, Erich

The evolution of complex molecular traits such as disulphide bridges often requires multiple mutations. The intermediate steps in such evolutionary trajectories are likely to be selectively neutral...

Limits on Replenishment of the Resting CD4+ T Cell Reservoir for HIV in Patients on HAART (2007)

Ahmad R. Sedaghat, Janet D. Siliciano, Timothy P. Brennan, Claus O. Wilke, Robert F. Siliciano

Whereas cells productively infected with human immunodeficiency virus type 1 (HIV-1) decay rapidly in the setting of highly active antiretroviral therapy (HAART), latently infected resting CD4+ T...

The stochastic edge in adaptive evolution (2007)

Brunet, Eric, Rouzine, Igor M., Wilke, Claus O.

In a recent article, Desai and Fisher (2007) proposed that the speed of adaptation in an asexual population is determined by the dynamics of the stochastic edge of the population, that is, by the...

The traveling wave approach to asexual evolution: Muller's ratchet and speed of adaptation (2007)

Rouzine, Igor M., Brunet, Eric, Wilke, Claus O.

We use traveling-wave theory to derive expressions for the rate of accumulation of deleterious mutations under Muller's ratchet and the speed of adaptation under positive selection in asexual...

Thermodynamics of Neutral Protein Evolution (2006)

Bloom, Jesse D, Raval, Alpan, Wilke, Claus O

Naturally evolving proteins gradually accumulate mutations while continuing to fold to thermodynamically stable native structures. This process of neutral protein evolution is an important mode of...

A Single Determinant Dominates the Rate of Yeast Protein Evolution (2006)

Drummond, D. Allan, Raval, Alpan, Wilke, Claus O.

A gene's rate of sequence evolution is among the most fundamental evolutionary quantities in common use, but what determines evolutionary rates has remained unclear. Here, we carry out the first...

A Single Determinant Dominates the Rate of Yeast Protein Evolution (2006)

Drummond, D. Allan, Raval, Alpan, Wilke, Claus O.

A gene's rate of sequence evolution is among the most fundamental evolutionary quantities in common use, but what determines evolutionary rates has remained unclear. Here, we carry out the first...

Structural Determinants of the Rate of Protein Evolution in Yeast (2006)

Bloom, Jesse D., Drummond, D. Allan, Arnold, Frances H., Wilke, Claus O.

We investigate how a protein's structure inuences the rate at which its sequence evolves. Our basic hypothesis is that proteins with highly designable structures (structures that are encoded by many...

Structural Determinants of the Rate of Protein Evolution in Yeast (2006)

Bloom, Jesse D., Drummond, D. Allan, Arnold, Frances H., Wilke, Claus O.

We investigate how a protein's structure influences the rate at which its sequence evolves. Our basic hypothesis is that proteins with highly designable structures (structures that are encoded by...

Why highly expressed proteins evolve slowly (2005)

Drummond, D. Allan, Bloom, Jesse D., Adami, Christoph, Wilke, Claus O., Arnold, Frances H.

Much recent work has explored molecular and population-genetic constraints on the rate of protein sequence evolution. The best predictor of evolutionary rate is expression level, for reasons that...

Tradeoff between short-term and long-term adaptation in a changing environment (2005)

Forster, Robert, Wilke, Claus O.

We investigate the competition dynamics of two microbial or viral strains that live in an environment that switches periodically between two states. One of the strains is adapted to the long-term...

Population genetics of translational robustness (2005)

Wilke, Claus O., Drummond, D. Allan

Recent work has shown that expression level is the main predictor of a gene’s evolutionary rate, and that more highly expressed genes evolve slower. A possible explanation for this observation...

Quasispecies can exist under neutral drift at finite population sizes (2005)

Forster, Robert, Adami, Christoph, Wilke, Claus O.

We investigate the evolutionary dynamics of a finite population of RNA sequences adapting to a neutral fitness landscape. Despite the lack of differential fitness between viable sequences, we observe...

Quasispecies theory in the context of population genetics (2005)

Wilke, Claus O.

Background: A number of recent papers have cast doubt on the applicability of the quasispecies concept to virus evolution, and have argued that population genetics is a more appropriate framework to...

Quasispecies theory in the context of population genetics (2005)

Wilke, Claus O

Abstract Background A number of recent papers have cast doubt on the applicability of the quasispecies concept to virus evolution, and have argued that population genetics is a more appropriate...

A single determinant for the rate of yeast protein evolution (2005)

Drummond, D. Allan, Raval, Alpan, Wilke, Claus O.

A gene's rate of sequence evolution is among the most fundamental evolutionary quantities in common use, but what determines evolutionary rates has remained unclear. Here, we show that the two most...

Why highly expressed proteins evolve slowly (2005)

Drummond, D. Allan, Bloom, Jesse D., Adami, Christoph, Wilke, Claus O., Arnold, Frances H.

Much recent work has explored molecular and population-genetic constraints on the rate of protein sequence evolution. The best predictor of evolutionary rate is expression level, for reasons which...

On the conservative nature of intragenic recombination (2005)

Drummond, D. Allan, Silberg, Jonathan J., Meyer, Michelle M., Wilke, Claus O., Arnold, Frances H.

Intragenic recombination rapidly creates protein sequence diversity compared with random mutation, but little is known about the relative effects of recombination and mutation on protein function....

Thermodynamic prediction of protein neutrality (2005)

Bloom, Jesse D., Silberg, Jonathan J., Wilke, Claus O., Drummond, D. Allan, Adami, Christoph, Arnold, Frances H.

We present a simple theory that uses thermodynamic parameters to predict the probability that a protein retains the wild-type structure after one or more random amino acid substitutions. Our theory...

Predicting the tolerance of proteins to random amino acid substitution (2005)

Claus O. Wilke, Jesse D. Bloom, Alpan Raval

ABSTRACT We have recently proposed a thermodynamic model that predicts the tolerance of proteins to random amino acid substitutions. Here we test this model against extensive simulations with compact...

A Single Determinant Dominates the Rate of Yeast Protein Evolution (2005)

Drummond, D. Allan, Raval, Alpan, Wilke, Claus O.

A gene's rate of sequence evolution is among the most fundamental evolutionary quantities in common use, but what determines evolutionary rates has remained unclear. Here, we carry out the first...

A Single Determinant Dominates the Rate of Yeast Protein Evolution (2005)

Drummond, D. Allan, Raval, Alpan, Wilke, Claus O.

A gene's rate of sequence evolution is among the most fundamental evolutionary quantities in common use, but what determines evolutionary rates has remained unclear. Here, we carry out the first...

Tradeoff between short-term and long-term adaptation in a changing environment (2004)

Forster, Robert, Wilke, Claus O.

We investigate the competition dynamics of two microbial or viral strains that live in an environment that switches periodically between two states. One of the strains is adapted to the long-term...

Thermodynamic Prediction of Protein Neutrality (2004)

Bloom, Jesse D., Silberg, Jonathan J., Wilke, Claus O., Drummond, D. Allan, Adami, Christoph, Arnold, Frances H.

We present a simple theory that uses thermodynamic parameters to predict the probability that a protein retains the wildtype structure after one or more random amino acid substitutions. Our theory...

Molecular clock in neutral protein evolution (2004)

Wilke, Claus O.

Background: A frequent observation in molecular evolution is that amino-acid substitution rates show an index of dispersion (that is, ratio of variance to mean) substantially larger than one. This...

Molecular clock in neutral protein evolution (2004)

Wilke, Claus O

Abstract Background A frequent observation in molecular evolution is that amino-acid substitution rates show an index of dispersion (that is, ratio of variance to mean) substantially larger than one....

Density-Dependent Selection in Vesicular Stomatitis Virus (2004)

Novella, Isabel, Reissig, Daniel D., Wilke, Claus O.

We used vesicular stomatitis virus to test the effect of complementation on the relative fitness of a deleterious mutant, monoclonal antibody-resistant mutant (MARM) N, in competition with its...

REPLICATION AT PERIODICALLY CHANGING MULTIPLICITY OF INFECTION PROMOTES STABLE COEXISTENCE OF COMPETING VIRAL POPULATIONS (2004)

Claus O. Wilke, Daniel D. Reissig, Isabel S. Novella

RNA viruses are widely used to study evolution experimentally. Many standard protocols of virus propagation and competition are done at nominally low multiplicity of infection (m.o.i.), but lead...

Avida: a software platform for research in computational evolutionary biology (2004)

Ofria, Charles, Wilke, Claus O.

Avida is a software platform for experiments with self-replicating and evolving computer programs. It provides detailed control over experimental settings and protocols, a large array of measurement...

Digital evolution in time-dependent fitness landscapes (2004)

Li, Ye, Wilke, Claus O.

We study the response of populations of digital organisms that adapt to a time-varying (periodic) fitness landscape of two oscillating peaks. We corroborate in general predictions from quasi-species...

The Speed of Adaptation in Large Asexual Populations (2004)

Wilke, Claus O.

In large asexual populations, beneficial mutations have to compete with each other for fixation. Here, I derive explicit analytic expressions for the rate of substitution and the mean beneficial...

Replication at periodically changing multiplicity of infection promotes stable coexistence of competing viral populations (2004)

Wilke, Claus O., Reissig, Daniel D., Novella, Isabel S.

RNA viruses are a widely used tool to study evolution experimentally. Many standard protocols of virus propagation and competition are done at nominally low multiplicity of infection (m.o.i.), but...

Stability and the Evolvability of Function in a Model Protein (2004)

Bloom, Jesse D, Wilke, Claus O, Arnold, Frances H, Adami, Christoph

Functional proteins must fold with some minimal stability to a structure that can perform a biochemical task. Here we use a simple model to investigate the relationship between the stability...

Evolution of Resource Competition between Mutually Dependent Digital Organisms (2004)

Johnson, Tyler J., Wilke, Claus O.

We study the emergence and dynamics of competing strains of digital organisms in a world with two depletable resources. Consumption of one resource produces the other resource as a by-product, and...

Phenotypic mixing and hiding may contribute to memory in viral quasispecies (2003)

Wilke, Claus O., Novella, Isabel S.

Background. In a number of recent experiments with food-and-mouth disease virus, a deleterious mutant, was found to avoid extinction and remain in the population for long periods of time. This...

Phenotypic mixing and hiding may contribute to memory in viral quasispecies (2003)

Wilke, Claus O., Novella, Isabel S.

Background: In a number of recent experiments with food-and-mouth disease virus, a deleterious mutant, RED, was found to avoid extinction and remain in the population for long periods of time. Since...

Phenotypic mixing and hiding may contribute to memory in viral quasispecies (2003)

Wilke, Claus O, Novella, Isabel S

Abstract Background In a number of recent experiments with food-and-mouth disease virus, a deleterious mutant, RED, was found to avoid extinction and remain in the population for long periods of...

Modeling stochastic clonal interference (2003)

Campos, Paulo R. A., Adami, Christoph, Wilke, Claus O.

We study the competition between several advantageous mutants in an asexual population (clonal interference) as a function of the time between the appearance of the mutants, their selective...

Compensatory mutations cause excess of antagonistic epistasis in RNA secondary structure folding (2003)

Wilke, Claus O, Lenski, Richard E, Adami, Christoph

Background: The rate at which fitness declines as an organism's genome accumulates random mutations is an important variable in several evolutionary theories. At an intuitive level, it might seem...

Does the Red Queen reign in the kingdom of digital organisms? (2003)

Wilke, Claus O.

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...

Compensatory mutations cause excess of antagonistic epistasis in RNA secondary structure folding (2003)

Wilke, Claus O., Lenski, Richard E., Adami, Christoph

Background: The rate at which fitness declines as an organism's genome accumulates random mutations is an important variable in several evolutionary theories. At an intuitive level, it might seem...

Compensatory mutations cause excess of antagonistic epistasis in RNA secondary structure folding (2003)

Wilke, Claus O, Lenski, Richard E, Adami, Christoph

Background The rate at which fitness declines as an organism's genome accumulates random mutations is an important variable in several evolutionary theories. At an intuitive level, it might seem...

Probability of fixation of an advantageous mutant in a viral quasispecies (2002)

Wilke, Claus O.

The probability that an advantageous mutant rises to fixation in a viral quasispecies is investigated in the framework of multi-type branching processes. Whether fixation is possible depends on the...

Viral evolution under the pressure of an adaptive immune system - optimal mutation rates for viral escape (2002)

Kamp, Christel, Wilke, Claus O., Adami, Christoph, Bornholdt, Stefan

Based on a recent model of evolving viruses competing with an adapting immune system [1], we study the conditions under which a viral quasispecies can maximize its growth rate. The range of mutation...

SELECTION FOR FITNESS VERSUS SELECTION FOR ROBUSTNESS IN RNA SECONDARY STRUCTURE FOLDING (2001)

Claus O. Wilke

I investigate the competition between two quasispecies residing on two disparate neutral networks. Under the assumption that the two neutral networks have different topologies and fitness levels, it...

Finite genome size can halt Muller's ratchet (2001)

Schoenmeyr, Tor, Wilke, Claus O.

We study the accumulation of deleterious mutations in a haploid, asexually reproducing population, using analytical models and computer simulations. We find that Muller's ratchet can come to a halt...

Optimal adaptive performance and delocalization in NK fitness landscapes (2001)

Campos, Paulo R. A., Adami, Christoph, Wilke, Claus O.

We investigate the evolutionary dynamics of a finite population of sequences adapting to NK fitness landscapes. We find that, unlike in the case of an infinite population, the average fitness in a...

Maternal effects in molecular evolution (2001)

Wilke, Claus O.

We introduce a model of molecular evolution in which the fitness of an individual depends both on its own and on the parent's genotype. The model can be solved by means of a nonlinear mapping onto...

Selection for Fitness vs. Selection for Robustness in RNA Secondary Structure Folding (2001)

Wilke, Claus O.

We investigate the competition between two quasispecies residing on two disparate neutral networks. Under the assumption that the two neutral networks have different topologies and fitness levels, it...

Adaptive evolution on neutral networks (2001)

Wilke, Claus O.

We study the evolution of large but finite asexual populations evolving in fitness landscapes in which all mutations are either neutral or strongly deleterious. We demonstrate that despite the...

Interaction between directional epistasis and average mutational effects (2000)

Wilke, Claus O., Adami, Christoph

We investigate the relationship between the average fitness decay due to single mutations and the strength of epistatic interactions in genetic sequences. We observe that epistatic interactions...

Genetic Algorithms in Time-Dependent Environments (2000)

Christopher Ronnewinkel Temporary, Christopher Ronnewinkel, Claus O. Wilke, Thomas Martinetz

The inuence of time-dependent tnesses on the in nite population dynamics of simple genetic algorithms (without crossover) is analyzed. Based on general arguments, a schematic phase diagram is...

Dynamic Fitness Landscapes in Molecular Evolution (1999)

Wilke, Claus O., Ronnewinkel, Christopher, Martinetz, Thomas

We study self-replicating molecules under externally varying conditions. Changing conditions such as temperature variations and/or alterations in the environment's resource composition lead to both...

Genetic Algorithms in Time-Dependent Environments (1999)

Ronnewinkel, Christopher, Wilke, Claus O., Martinetz, Thomas

The influence of time-dependent fitnesses on the infinite population dynamics of simple genetic algorithms (without crossover) is analyzed. Based on general arguments, a schematic phase diagram is...

Molecular Evolution in Time Dependent Environments (1999)

Wilke, Claus O., Ronnewinkel, Christopher, Martinetz, Thomas

The quasispecies theory is studied for dynamic replication landscapes. A meaningful asymptotic quasispecies is defined for periodic time dependencies. The quasispecies' composition is constantly...

Adaptive walks on time-dependent fitness landscapes (1999)

Wilke, Claus O., Martinetz, Thomas

The idea of adaptive walks on fitness landscapes as a means of studying evolutionary processes on large time scales is extended to fitness landscapes that are slowly changing over time. The influence...

Genetic Algorithms in Time-Dependent Environments (1999)

Christopher Ronnewinkel, Claus O. Wilke, Thomas Martinetz

The influence of time-dependent fitnesses on the infinite population dynamics of simple genetic algorithms (without crossover) is analyzed. Based on general arguments, a schematic phase diagram is...

Molecular Evolution in Time-Dependent Environments (1999)

Claus O. Wilke, Christopher Ronnewinkel, Thomas Martinetz

The quasispecies theory is studied for dynamic replication landscapes. A meaningful asymptotic quasispecies is de ned for periodic time dependencies. The quasispecies' composition is constantly...

Molecular Evolution in timedependent Environments (1999)

Claus O. Wilke, Christopher Ronnewinkel, Thomas Martinetz

Abstract. The quasispecies theory is studied for dynamic replication landscapes. A meaningful asymptotic quasispecies is defined for periodic time dependencies. The quasispecies ’ composition is...

Lifetimes of agents under external stress (1998)

Wilke, Claus O., Martinetz, Thomas

An exact formula for the distribution of lifetimes in coherent-noise models and related models is derived. For certain stress distributions, this formula can be analytically evaluated and yields...

Evolution in time-dependent fitness landscapes (1998)

Wilke, Claus O.

Evolution in changing environments is an important, but little studied aspect of the theory of evolution. The idea of adaptive walks in fitness landscapes has triggered a vast amount of research and...

Evolution in time-dependent fitness landscapes (1998)

Claus O. Wilke, Claus O. Wilke

Evolution in changing environments is an important, but little studied aspect of the theory of evolution. The idea of adaptive walks in fitness landscapes has triggered a vast amount of research and...

Density-Dependent Selection in Vesicular Stomatitis Virus

Novella, Isabel S., Reissig, Daniel D., Wilke, Claus O.

We used vesicular stomatitis virus to test the effect of complementation on the relative fitness of a deleterious mutant, monoclonal antibody-resistant mutant (MARM) N, in competition with its...

Thermodynamic prediction of protein neutrality

Bloom, Jesse D., Silberg, Jonathan J., Wilke, Claus O., Drummond, D. Allan, Adami, Christoph, Arnold, Frances H.

We present a simple theory that uses thermodynamic parameters to predict the probability that a protein retains the wild-type structure after one or more random amino acid substitutions. Our theory...

On the conservative nature of intragenic recombination

Drummond, D. Allan, Silberg, Jonathan J., Meyer, Michelle M., Wilke, Claus O., Arnold, Frances H.

Intragenic recombination rapidly creates protein sequence diversity compared with random mutation, but little is known about the relative effects of recombination and mutation on protein function....

Stability and the Evolvability of Function in a Model Protein

Bloom, Jesse D., Wilke, Claus O., Arnold, Frances H., Adami, Christoph

Functional proteins must fold with some minimal stability to a structure that can perform a biochemical task. Here we use a simple model to investigate the relationship between the stability...

Why highly expressed proteins evolve slowly

Drummond, D. Allan, Bloom, Jesse D., Adami, Christoph, Wilke, Claus O., Arnold, Frances H.

Much recent work has explored molecular and population-genetic constraints on the rate of protein sequence evolution. The best predictor of evolutionary rate is expression level, for reasons that...

Co-infection Weakens Selection Against Epistatic Mutations in RNA Viruses

Froissart, Rémy, Wilke, Claus O., Montville, Rebecca, Remold, Susanna K., Chao, Lin, Turner, Paul E.

Co-infection may be beneficial in large populations of viruses because it permits sexual exchange between viruses that is useful in combating the mutational load. This advantage of sex should be...

Population Genetics of Translational Robustness

Wilke, Claus O., Drummond, D. Allan

Recent work has shown that expression level is the main predictor of a gene's evolutionary rate and that more highly expressed genes evolve slower. A possible explanation for this observation is...

Probability of fixation of an advantageous mutant in a viral quasispecies.

Wilke, Claus O

The probability that an advantageous mutant rises to fixation in a viral quasispecies is investigated in the framework of multitype branching processes. Whether fixation is possible depends on the...

The speed of adaptation in large asexual populations.

Wilke, Claus O

In large asexual populations, beneficial mutations have to compete with each other for fixation. Here, I derive explicit analytic expressions for the rate of substitution and the mean beneficial...

Residual Human Immunodeficiency Virus Type 1 Viremia in Some Patients on Antiretroviral Therapy Is Dominated by a Small Number of Invariant Clones Rarely Found in Circulating CD4+ T Cells†

Bailey, Justin R., Sedaghat, Ahmad R., Kieffer, Tara, Brennan, Timothy, Lee, Patricia K., Wind-Rotolo, Megan, ...

Antiretroviral therapy can reduce human immunodeficiency virus type 1 (HIV-1) viremia to below the detection limit of ultrasensitive clinical assays (50 copies of HIV-1 RNA/ml). However, latent HIV-1...

Predicting the Tolerance of Proteins to Random Amino Acid Substitution

Wilke, Claus O., Bloom, Jesse D., Drummond, D. Allan, Raval, Alpan

We have recently proposed a thermodynamic model that predicts the tolerance of proteins to random amino acid substitutions. Here we test this model against extensive simulations with compact lattice...

Density-Dependent Selection in Vesicular Stomatitis Virus

Novella, Isabel S., Reissig, Daniel D., Wilke, Claus O.

We used vesicular stomatitis virus to test the effect of complementation on the relative fitness of a deleterious mutant, monoclonal antibody-resistant mutant (MARM) N, in competition with its...

Thermodynamic prediction of protein neutrality

Bloom, Jesse D., Silberg, Jonathan J., Wilke, Claus O., Drummond, D. Allan, Adami, Christoph, Arnold, Frances H.

We present a simple theory that uses thermodynamic parameters to predict the probability that a protein retains the wild-type structure after one or more random amino acid substitutions. Our theory...

On the conservative nature of intragenic recombination

Drummond, D. Allan, Silberg, Jonathan J., Meyer, Michelle M., Wilke, Claus O., Arnold, Frances H.

Intragenic recombination rapidly creates protein sequence diversity compared with random mutation, but little is known about the relative effects of recombination and mutation on protein function....

Why highly expressed proteins evolve slowly

Drummond, D. Allan, Bloom, Jesse D., Adami, Christoph, Wilke, Claus O., Arnold, Frances H.

Much recent work has explored molecular and population-genetic constraints on the rate of protein sequence evolution. The best predictor of evolutionary rate is expression level, for reasons that...

Stability and the Evolvability of Function in a Model Protein

Bloom, Jesse D., Wilke, Claus O., Arnold, Frances H., Adami, Christoph

Functional proteins must fold with some minimal stability to a structure that can perform a biochemical task. Here we use a simple model to investigate the relationship between the stability...

Predicting the Tolerance of Proteins to Random Amino Acid Substitution

Wilke, Claus O., Bloom, Jesse D., Drummond, D. Allan, Raval, Alpan

We have recently proposed a thermodynamic model that predicts the tolerance of proteins to random amino acid substitutions. Here we test this model against extensive simulations with compact lattice...

Co-infection Weakens Selection Against Epistatic Mutations in RNA Viruses

Froissart, Rémy, Wilke, Claus O., Montville, Rebecca, Remold, Susanna K., Chao, Lin, Turner, Paul E.

Co-infection may be beneficial in large populations of viruses because it permits sexual exchange between viruses that is useful in combating the mutational load. This advantage of sex should be...

Population Genetics of Translational Robustness

Wilke, Claus O., Drummond, D. Allan

Recent work has shown that expression level is the main predictor of a gene's evolutionary rate and that more highly expressed genes evolve slower. A possible explanation for this observation is...

Probability of fixation of an advantageous mutant in a viral quasispecies.

Wilke, Claus O

The probability that an advantageous mutant rises to fixation in a viral quasispecies is investigated in the framework of multitype branching processes. Whether fixation is possible depends on the...

The speed of adaptation in large asexual populations.

Wilke, Claus O

In large asexual populations, beneficial mutations have to compete with each other for fixation. Here, I derive explicit analytic expressions for the rate of substitution and the mean beneficial...

Residual Human Immunodeficiency Virus Type 1 Viremia in Some Patients on Antiretroviral Therapy Is Dominated by a Small Number of Invariant Clones Rarely Found in Circulating CD4+ T Cells†

Bailey, Justin R., Sedaghat, Ahmad R., Kieffer, Tara, Brennan, Timothy, Lee, Patricia K., Wind-Rotolo, Megan, ...

Antiretroviral therapy can reduce human immunodeficiency virus type 1 (HIV-1) viremia to below the detection limit of ultrasensitive clinical assays (50 copies of HIV-1 RNA/ml). However, latent HIV-1...

Thermodynamics of Neutral Protein Evolution

Bloom, Jesse D., Raval, Alpan, Wilke, Claus O.

Naturally evolving proteins gradually accumulate mutations while continuing to fold to stable structures. This process of neutral evolution is an important mode of genetic change and forms the basis...

Limits on Replenishment of the Resting CD4+ T Cell Reservoir for HIV in Patients on HAART

Sedaghat, Ahmad R, Siliciano, Janet D, Brennan, Timothy P, Wilke, Claus O, Siliciano, Robert F

Whereas cells productively infected with human immunodeficiency virus type 1 (HIV-1) decay rapidly in the setting of highly active antiretroviral therapy (HAART), latently infected resting CD4+ T...

The Stochastic Edge in Adaptive Evolution

Brunet, Éric, Rouzine, Igor M., Wilke, Claus O.

In a recent article, Desai and Fisher proposed that the speed of adaptation in an asexual population is determined by the dynamics of the stochastic edge of the population, that is, by the emergence...

Rapid Adaptive Amplification of Preexisting Variation in an RNA Virus▿

Dutta, Ranendra N., Rouzine, Igor M., Smith, Sarah D., Wilke, Claus O., Novella, Isabel S.

The amount and nature of preexisting variation in a population of RNA viruses is an important determinant of the virus's ability to adapt rapidly to a changed environment. However, direct...

Decay dynamics of HIV-1 depend on the inhibited stages of the viral life cycle

Sedaghat, Ahmad R., Dinoso, Jason B., Shen, Lin, Wilke, Claus O., Siliciano, Robert F.

The time to suppression of HIV-1 viremia to below the limit of detection of standard clinical assays is an important prognostic indicator for patients on highly active antiretroviral therapy (HAART)....

Detecting Clusters of Mutations

Zhou, Tong, Enyeart, Peter J., Wilke, Claus O.

Positive selection for protein function can lead to multiple mutations within a small stretch of DNA, i.e., to a cluster of mutations. Recently, Wagner proposed a method to detect such mutation...

Lethal Mutagenesis of Bacteria

Bull, James J., Wilke, Claus O.

Lethal mutagenesis, the killing of a microbial pathogen with a chemical mutagen, is a potential broad-spectrum antiviral treatment. It operates by raising the genomic mutation rate to the point that...

A Linear Relationship between Fitness and the Logarithm of the Critical Bottleneck Size in Vesicular Stomatitis Virus Populations▿ §

Novella, Isabel S., Dutta, Ranendra N., Wilke, Claus O.

We explored the relationship between fitness change and population size during transmission in vesicular stomatitis populations of very high fitness. The results show a linear correlation between the...