A model for background selection in non-equilibrium populations
This article has been Reviewed by the following groups
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
- Evaluated articles (Peer Community in Evolutionary Biology)
Abstract
In many taxa, levels of genetic diversity are observed to vary along their genome. The framework of background selection models this variation in terms of linkage to constrained sites, and recent applications have been able to explain a large portion of the variation in human genomes. However, these studies have also yielded conflicting results, stemming from two key limitations. First, existing models are inaccurate in a critical region of parameter space ( N e s ~ −1), where the local reduction in diversity is sharpest. Second, they assume a constant population size over time. Here, we develop predictions for diversity under background selection based on the Hill-Robertson system of two-locus statistics, which allows for population size changes. We treat the joint effect of multiple selected loci independently, but we show that interference among them is well captured through local rescaling of mutation, recombination and selection in an iterative procedure that converges quickly. We further accommodate existing background selection theory to non-equilibrium demography, bridging the gap between weak and strong selection. Simulations show that our predictions are accurate across the entire range of selection coefficients. We characterize the temporal dynamics of linked selection under population size changes and demonstrate that patterns of diversity can be misinterpreted by other models. Specifically, biases due to the incorrect assumption of equilibrium carry over to downstream inferences of the distribution of fitness effects and deleterious mutation rate. Jointly modeling demography and linked selection therefore improves our understanding of the genomic landscape of diversity, which will help refine inferences of linked selection in humans and other species.
Article activity feed
-
Linked selection is a major factor determining patterns of diversity along the genomes of many species. As it results from the ubiquitous process of selection against deleterious alleles, background selection (BGS) is often considered the predominant form of linked selection.
Classic models of BGS, however, often ignore weakly deleterious mutations and assume populations are at demographic equilibrium. Real genomes include many weakly selected alleles, and real populations are rarely at equilibrium. Classic BGS models fail to incorporate these dynamics, and in realistic scenarios can incorrectly predict changes in diversity along the genome, which in turn impacts downstream evolutionary inference. While previous work had identified some of these problems, formal approaches to resolving them have been lacking.
Barroso and Ragsdale …
Linked selection is a major factor determining patterns of diversity along the genomes of many species. As it results from the ubiquitous process of selection against deleterious alleles, background selection (BGS) is often considered the predominant form of linked selection.
Classic models of BGS, however, often ignore weakly deleterious mutations and assume populations are at demographic equilibrium. Real genomes include many weakly selected alleles, and real populations are rarely at equilibrium. Classic BGS models fail to incorporate these dynamics, and in realistic scenarios can incorrectly predict changes in diversity along the genome, which in turn impacts downstream evolutionary inference. While previous work had identified some of these problems, formal approaches to resolving them have been lacking.
Barroso and Ragsdale address non-equilibrium demography and weak BGS with new theoretical work that builds on Hill-Robertson two-locus statistics. They show via simulation the accuracy of their new approach, demonstrate how non-equilibrium dynamics can bias models of BGS that rely on classic equilibrium assumptions, and how incorporating the full range of selection coefficients -- including weakly selected alleles -- improves the prediction of diversity along the genome. They then document how biases from using equilibrium theory can impact one example of downstream inference, the estimation of the distribution of fitness effects of new mutations.
This is a significant step forward in our understanding of, and, crucially, our ability to model BGS. As predictions of BGS are frequently incorporated into a wide range of analyses and models, this work will advance our understanding of the interaction of different evolutionary forces that pattern genetic diversity along genomes.
References
Gustavo V. Barroso, Aaron P. Ragsdale (2025) A model for background selection in non-equilibrium populations. bioRxiv, ver.3 peer-reviewed and recommended by PCI Evolutionary Biology https://doi.org/10.1101/2025.02.19.639084
-
