Related papers: Strong Selection Significantly Increases Epistatic…
Proteins evolve through complex sequence spaces, with fitness landscapes serving as a conceptual framework that links sequence to function. Fitness landscapes can be smooth, where multiple similarly accessible evolutionary paths are…
We analyze 14,651 HIV1 reverse transcriptase (HIV RT) sequences from the Stanford HIV Drug Resistance Database labeled with treatment regimen in order to study the evolution this enzyme under drug selection in the clinic. Our goal is to…
Protein sequence data from nature exhibits survivorship bias: we only observe data from those organisms that survive and reproduce, while non-functional protein mutations are eliminated by natural selection. Thus, predicting whether a…
An exactly solvable model based on the topology of a protein native state is applied to identify bottlenecks and key-sites for the folding of HIV-1 Protease. The predicted sites are found to correlate well with clinical data on resistance…
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 have remained unexplained. Here, we…
The evolution of antimicrobial resistance generally occurs in an environment where antimicrobial concentration is variable, which has dramatic consequences on the microorganisms' fitness landscape, and thus on the evolution of resistance.…
An elastic spring network is an example of evolvable matter. It can be pruned to couple separated pairs of nodes so that when a strain is applied to one of them, the other responds either in-phase or out-of-phase. This produces two pruned…
We are living in an uncertain and dynamically changing world, where optimal decision-making under uncertainty is directly linked to the survival of species. However, evolutionary selection pressures that shape value-based decision-making…
The length distribution of proteins measured in amino acids follows the CoHSI (Conservation of Hartley-Shannon Information) probability distribution. In previous papers we have verified various predictions of this using the Uniprot database…
Selective sweeps are typically associated with a local reduction of genetic diversity around the adaptive site. However, selective sweeps can also quickly carry neutral mutations to observable population frequencies if they arise early in a…
Emerging empirical and theoretical thinking about human aging places considerable value upon the role of the environment as a major factor which can promote prolonged healthy longevity. Our contemporary, information-rich environment is…
The fitness landscape - the mapping between genotypes and fitness - determines properties of the process of adaptation. Several small genetic fitness landscapes have recently been built by selecting a handful of beneficial mutations and…
Mutation rate is a key determinant of the pace as well as outcome of evolution, and variability in this rate has been shown in different scenarios to play a key role in evolutionary adaptation and resistance evolution under stress caused by…
Since penicillin was discovered about 90 years ago, we have become used to using drugs to eradicate unwanted pathogenic cells. However, using drugs to kill bacteria, viruses or cancer cells has the serious side effect of selecting for…
Recombinant Inbred Lines derived from divergent parental lines can display extensive segregation distortion and long-range linkage disequilibrium (LD) between distant loci. These genomic signatures are consistent with epistatic selection…
We carry out a theoretical study of the vibrational and relaxation properties of naturally-occurring proteins with the purpose of characterizing both the folding and equilibrium thermodynamics. By means of a suitable model we provide a full…
Motivation: Protein interactions are fundamental building blocks of biochemical reaction systems underlying cellular functions. The complexity and functionality of such systems emerge not from the protein interactions themselves but from…
Mechanisms of immunity, and of the host-pathogen interactions in general are among the most fundamental problems of medicine, ecology, and evolution studies. Here, we present a microscopic, protein-level, sequence-based model of immune…
Frequency-dependent selection reflects the interaction between different species as they battle for limited resources in their environment. In a stochastic evolutionary game the species relative fitnesses guides the evolutionary dynamics…
Evolutionary dynamics and patterns of molecular evolution are strongly influenced by selection on linked regions of the genome, but our quantitative understanding of these effects remains incomplete. Recent work has focused on predicting…