Related papers: Epistasis not needed to explain low dN/dS
Epistatic interactions between mutations add substantial complexity to adaptive landscapes, and are often thought of as detrimental to our ability to predict evolution. Yet, patterns of global epistasis, in which the fitness effect of a…
The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…
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…
Despite the importance of a thermodynamically stable structure with a conserved fold for protein function, almost all evolutionary models neglect site-site correlations that arise from physical interactions between neighboring amino acid…
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…
Proteins are essential for maintaining life. For example, knowing the structure of a protein, cell regulatory mechanisms of organisms can be modeled, supporting the development of disease treatments or the understanding of relationships…
Evolutionary trajectories and phenotypic states available to cell populations are ultimately dictated by intermolecular interactions between DNA, RNA, proteins, and other molecular species. Here we study how evolution of gene regulation in…
Evolutionary models measure the probability of amino acid substitutions occurring over different evolutionary distances. We examine various evolutionary models based on empirically derived amino acid substitution matrices. The models are…
Natural protein sequences that self-assemble to form globular structures are compact with high packing densities in the folded states. It is known that proteins unfold upon addition of denaturants, adopting random coil structures. The…
Dominance is usually considered a constant value that describes the relative difference in fitness or phenotype between heterozygotes and the average of homozygotes at a focal polymorphic locus. However, the observed dominance can vary with…
One of the most puzzling and unsolved challenges in molecular biology is understanding how proteins fold. Despite having advanced predictive tools that can accurately estimate the native structures of proteins, we still lack a comprehensive…
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 between mutations are correlated to the…
Most living systems rely on double-stranded DNA (dsDNA) to store their genetic information and perpetuate themselves. This biological information has been considered the main target of evolution. However, here we show that symmetries and…
The role of positive selection in human evolution remains controversial. On the one hand, scans for positive selection have identified hundreds of candidate loci and the genome-wide patterns of polymorphism show signatures consistent with…
Darwinian evolution can be illustrated as an uphill walk in a landscape, where the surface consists of genotypes, the height coordinates represent fitness, and each step corresponds to a point mutation. Epistasis, roughly defined as the…
Much information is stored in amino acid composition of protein and base composition of DNA. We simulated the evolution of amino acid frequencies and genomic GC content by a linguistic model. It is showed that the evolution of genetic code…
Although many phenotypic traits are determined by a large number of genetic variants, the behavior of allele frequencies in a polygenic trait is not completely understood. The problem is especially challenging when the quantitative trait of…
The protein folding problem must ultimately be solved on all length scales from the atomic up through a hierarchy of complicated structures. By analyzing the stability of the folding process using physics and mathematics, this paper shows…
Genotypic fitness landscapes are constructed by assessing the fitness of all possible combinations of a given number of mutations. In the last years, several experimental fitness landscapes have been completely resolved. As fitness…
Single-molecule force spectroscopy has opened a new field of research in molecular biophysics and biochemistry. Pulling experiments on individual proteins permit us to monitor conformational transitions with high temporal resolution and…