Related papers: Protein overabundance is driven by growth robustne…
The processes of gene expression are inherently stochastic, even for essential genes required for growth. How does the cell maximize fitness in light of noise? To answer this question, we build a mathematical model to explore the trade-off…
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…
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 selection for proteins which fold…
How do living cells achieve sufficient abundances of functional protein complexes while minimizing promiscuous non-functional interactions? Here we study this problem using a first-principle model of the cell whose phenotypic traits are…
Translation of proteins is a fundamental part of gene expression that is mediated by ribosomes. As ribosomes significantly contribute to both cellular mass and energy consumption, achieving efficient management of the ribosome population is…
BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar…
The number of ribosomes in a cell is considered as limiting, and gene expression is thus largely determined by their cellular concentration. In this work we develop a toy model to study the trade-off between the ribosomal supply and the…
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 requirement and the capacity of a protein to…
We show how concepts from statistical physics, such as order parameter, thermodynamic limit, and quantum phase transition, translate into biological concepts in mutation-selection models for sequence evolution and can be used there. The…
Despite growth being fundamental to all aspects of cell biology, we do not yet know its organizing principles in eukaryotic cells. Classic models derived from the bacteria E. coli posit that protein-synthesis rates are set by mass-action…
A fundamental question for evolutionary biology is why rates of evolution vary dramatically between proteins. Perhaps surprisingly, it is controversial how much a protein's functional importance affects its rate of evolution. In most…
The interaction cutoff contribution to the ruggedness of protein-protein energy landscape (the artificial ruggedness) is studied in terms of relative energy fluctuations for 1/r^n potentials based on a simplistic model of a protein complex.…
A classic problem in metabolism is that fast-proliferating cells use seemingly wasteful fermentation for energy biogenesis in the presence of sufficient oxygen. This counterintuitive phenomenon, known as overflow metabolism or the Warburg…
Bacteria evolve resistance to antibiotics by a multitude of mechanisms. A central, yet unsolved question is how resistance evolution affects cell growth at different drug levels. Here we develop a fitness model that predicts growth rates of…
The twenty protein coding amino acids are found in proteomes with different relative abundances. The most abundant amino acid, leucine, is nearly an order of magnitude more prevalent than the least abundant amino acid, cysteine. Amino acid…
An accurate estimation of the Protein Space size, in light of the factors that govern it, is a long-standing problem and of paramount importance in evolutionary biology, since it determines the nature of protein evolvability. A simple…
Classical population genetics a priori assigns fitness to alleles without considering molecular or functional properties of proteins that these alleles encode. Here we study population dynamics in a model where fitness can be inferred from…
Robustness is often regarded as a critical future challenge for real-world applications, where stability is essential. However, as models often learn tasks in a similar order, we hypothesize that easier tasks will be easier regardless of…
Constraints on changes in expression levels across all cell components imposed by the steady growth of cells have recently been discussed both experimentally and theoretically. By assuming a small environmental perturbation and considering…
Mutations in a microbial population can increase the frequency of a genotype not only by increasing its exponential growth rate, but also by decreasing its lag time or adjusting the yield (resource efficiency). The contribution of multiple…