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This piece serves two purposes. Firstly, it aims at elucidating the role of epistasis in shaping, at a molecular level, the evolutionary paths of proteins, as well as the extent to which these epistatic effects are the outcome of an…
Evolution has fascinated quantitative and physical scientists for decades: how can the random process of mutation, recombination, and duplication of genetic information generate the diversity of life? What determines the rate of evolution?…
Proteins are a matter of dual nature. As a physical object, a protein molecule is a folded chain of amino acids with multifarious biochemistry. But it is also an instantiation along an evolutionary trajectory determined by the function…
The interconnected processes of protein folding, mutations, epistasis, and evolution have all been the subject of extensive analysis throughout the years due to their significance for structural and evolutionary biology. The origin…
Protein evolution underpins life, and understanding its behavior as a system is of great importance. However, our current models of protein evolution are arguably too simplistic to allow quantitative interpretation and prediction of…
Proteins, by virtue of their central role in most biological processes, represent one of the key subjects of the study of molecular evolution. Inherent to the indispensability of proteins for living cells is the fact that a given protein…
Proteins have evolved through mutations, amino acid substitutions, since life appeared on Earth, some 109 years ago. The study of these phenomena has been of particular significance because of their impact on protein stability, function,…
There is an intrinsic relationship between the molecular evolution in primordial period and the properties of genomes and proteomes of contemporary species. The genomic data may help us understand the driving force of evolution of life at…
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 ability to absorb mutations while retaining structure and function, or mutational robustness, is a remarkable property of natural proteins. In this Letter, we use a computational model of organismic evolution [Zeldovich et al, PLOS Comp…
Binding interactions between proteins and other molecules mediate numerous cellular processes, including metabolism, signaling, and regulation of gene expression. These interactions evolve in response to changes in the protein's chemical or…
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 primary aim of this work is to explore how proteins point mutations impact their marginal stability and, hence, their evolvability. With this purpose, we show that the use of four classic notions, namely, those from Leibniz & Kant…
Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution…
One of the classical questions in evolutionary biology is how evolutionary processes are coupled at the gene and species level. With this motivation, we compare the topological properties (mainly the depth scaling, as a characterization of…
The fitness contribution of an allele at one genetic site may depend on alleles at other sites, a phenomenon known as epistasis. Epistasis can profoundly influence the process of evolution in populations under selection, and can shape the…
The protein folding problem has attracted an increasing attention from physicists. The problem has a flavor of statistical mechanics, but possesses the most common feature of most biological problems -- the profound effects of evolution. I…
We apply the theory of learning to physically renormalizable systems in an attempt to develop a theory of biological evolution, including the origin of life, as multilevel learning. We formulate seven fundamental principles of evolution…
How proteins fold remains a central unsolved problem in biology. While the idea of a folding code embedded in the amino acid sequence was introduced more than 6 decades ago, this code remains undefined. While we now have powerful predictive…
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…