The effects of hitchhiking and repulsion of deleterious alleles on linkage disequilibrium during a selective sweep
- 1University of California, Los Angeles
Abstract
Deleterious mutations are abundant in nature. Consequently, when an adaptive mutation arises, it will likely land on a haplotype with several deleterious mutations. While deleterious mutations may hitchhike with the adaptive variant, deleterious mutations are less likely to be found on the same haplotype with each other due to repulsion (i.e. Hill Robertson interference). Both hitchhiking and repulsion shape patterns of linkage disequilibrium (LD), but their simultaneous impact on LD have not been fully understood, leaving a gap in accurate inference of selection from genomic data. Here, we investigate patterns of LD during a sweep using simulations across a wide range of evolutionary parameters. On average, LD is elevated between pairs of intermediate frequency nonsynonymous variants relative to synonymous variants. This occurs because nonsynonymous variants, which are presumably deleterious, are more likely to rise to high frequency via hitchhiking rather than drift and thus will be predominantly found on the sweeping haplotype. However, we find that this elevation does not occur across all distances: when nonsynonymous variants are either too close to each other or too far from the adaptive locus, repulsion between deleterious variants results in lower LD among nonsynonymous variants. This results in a characteristic "criss-crossing" of LD. We find that criss-crossing is a feature of empirical data from Clostridioides difficile, a pathogen that has undergone several selective sweeps. However, some sweeps show elevation of nonsynonymous LD over synonymous LD across all distances. These sweeps have been previously identified to bear complex adaptations, and moreover, harbor elevated nucleotide diversity. Consistent with this, we demonstrate that lack of criss-crossing can arise when adaptation proceeds via epistatic, multi-locus architecture or introgression.
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BibTeX
@misc{weissman2026effects,
title = {{The effects of hitchhiking and repulsion of deleterious alleles on linkage disequilibrium during a selective sweep}},
author = {M. Weissman and K. E. Lohmueller and N. R. Garud},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.01.756034},
url = {https://www.biorxiv.org/content/10.64898/2026.10.01.756034v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - The effects of hitchhiking and repulsion of deleterious alleles on linkage disequilibrium during a selective sweep
AU - M. Weissman
AU - K. E. Lohmueller
AU - N. R. Garud
PY - 2026
DA - 2026/10/01
PB - bioRxiv
DO - 10.64898/2026.10.01.756034
UR - https://www.biorxiv.org/content/10.64898/2026.10.01.756034v1
AB - Deleterious mutations are abundant in nature. Consequently, when an adaptive mutation arises, it will likely land on a haplotype with several deleterious mutations. While deleterious mutations may hitchhike with the adaptive variant, deleterious mutations are less likely to be found on the same haplotype with each other due to repulsion (i.e. Hill Robertson interference). Both hitchhiking and repulsion shape patterns of linkage disequilibrium (LD), but their simultaneous impact on LD have not been fully understood, leaving a gap in accurate inference of selection from genomic data. Here, we investigate patterns of LD during a sweep using simulations across a wide range of evolutionary parameters. On average, LD is elevated between pairs of intermediate frequency nonsynonymous variants relative to synonymous variants. This occurs because nonsynonymous variants, which are presumably deleterious, are more likely to rise to high frequency via hitchhiking rather than drift and thus will be predominantly found on the sweeping haplotype. However, we find that this elevation does not occur across all distances: when nonsynonymous variants are either too close to each other or too far from the adaptive locus, repulsion between deleterious variants results in lower LD among nonsynonymous variants. This results in a characteristic "criss-crossing" of LD. We find that criss-crossing is a feature of empirical data from Clostridioides difficile, a pathogen that has undergone several selective sweeps. However, some sweeps show elevation of nonsynonymous LD over synonymous LD across all distances. These sweeps have been previously identified to bear complex adaptations, and moreover, harbor elevated nucleotide diversity. Consistent with this, we demonstrate that lack of criss-crossing can arise when adaptation proceeds via epistatic, multi-locus architecture or introgression.
ER -