Inferring epistasis from genomic data with comparable mutation and outcrossing rate
We consider a population evolving due to mutation, selection and recombination, where selection includes single-locus terms (additive fitness) and two-loci terms (pairwise epistatic fitness). We further consider the problem of inferring fitness in the evolutionary dynamics from one or several snap-shots of the distribution of genotypes in the population. In the recent literature this has been done by applying the Quasi-Linkage Equilibrium (QLE) regime first obtained by Kimura in the limit of high recombination. Here we show that the approach also works in the interesting regime where the effects of mutations are comparable to or larger than recombination. This leads to a modified main epistatic fitness inference formula where the rates of mutation and recombination occur together. We also derive this formula using by a previously developed Gaussian closure that formally remains valid when recombination is absent. The findings are validated through numerical simulations.
Code (0)
등록된 구현이 없습니다.
Tasks
validSimilar Papers 제목 키워드 기반
The context-dependence of mutations: a linkage of formalisms
Defining the extent of epistasis - the non-independence of the effects of mutations - is essential for understanding the relationship of genotype, phenotype, and fitness in biological systems. The applications cover many…
Temporal epistasis inference from more than 3,500,000 SARS-CoV-2 Genomic Sequences
We use Direct Coupling Analysis (DCA) to determine epistatic interactions between loci of variability of the SARS-CoV-2 virus, segmenting genomes by month of sampling. We use full-length, high-quality genomes from the GI…
The Origin of Mutational Epistasis
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.…
Protein FoldingRole of epistasis on the fixation probability of a non-mutator in an adapted asexual population
The mutation rate of a well adapted population is prone to reduction so as to have a lower mutational load. We aim to understand the role of epistatic interactions between the fitness affecting mutations in this process.…
Direct Coupling Analysis of Epistasis in Allosteric Materials
In allosteric proteins, the binding of a ligand modifies function at a distant active site. Such allosteric pathways can be used as target for drug design, generating considerable interest in inferring them from sequence…
Drug Design