Inferring epistasis from genomic data with comparable mutation and outcrossing rate

Abstract

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.

arXiv comment16 pages, 9 figures. Substantial revision from second version, previous suggestions and comments gratefully acknowledged

References in corpus (13)

• Direct-coupling analysis of residue co-evolution captures native contacts across many protein families
• Inverse statistical problems: from the inverse Ising problem to data science
• Inverse Statistical Physics of Protein Sequences: A Key Issues Review
• Stochastic Models of Evolution in Genetics, Ecology and Linguistics
• Statistical physics of pairwise probability models
• Competition between recombination and epistasis can cause a transition from allele to genotype selection
• Statistical Genetics and Evolution of Quantitative Traits
• Coalescence, genetic diversity in sexual populations under selection
• Global analysis of more than 50,000 SARS-Cov-2 genomes reveals epistasis between 8 viral genes
• Evolution of molecular phenotypes under stabilizing selection
• Survival of the simplest: the cost of complexity in microbial evolution
• Inferring genetic fitness from genomic data
• Gaussian Closure Scheme in the Quasi-Linkage Equilibrium Regime of Evolving Genome Populations

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