The effects of hitchhiking and repulsion of deleterious alleles on linkage disequilibrium during a selective sweep

Deleterious mutations are rampant in nature. When advantageous mutations emerge, they often inherit a companion of harmful variants due to a phenomenon known as "repulsion" or Hill Robertson interference. This interplay between hitchhiking and repulsion greatly affects the patterns of linkage disequilibrium (LD) during a selective sweep. However, the simultaneous influence of these two processes on LD has remained unclear, creating a gap in our ability to accurately infer selection using genomic data.

In the study, researchers simulated patterns of LD across various evolutionary parameters. They discovered that LD tends to be higher between pairs of intermediate frequency nonsynonymous variants compared to synonymous variants. This occurs because nonsynonymous variants, which are likely to be deleterious, are more likely to become common due to hitchhiking rather than random drift. As a result, they are predominantly found on the haplotype undergoing selection.

However, this elevation of LD between nonsynonymous variants does not occur uniformly across all distances. When nonsynonymous variants are too close to each other or too far from the adaptive locus, repulsion between deleterious variants leads to lower LD among nonsynonymous variants. This results in a distinctive "criss-crossing" pattern of LD. This phenomenon has been observed in empirical data from Clostridioides difficile, a pathogen that has experienced several selective sweeps.

Interestingly, some sweeps exhibit an elevation of nonsynonymous LD over synonymous LD across all distances. These sweeps have been identified to possess complex adaptations and elevated nucleotide diversity. The absence of criss-crossing in these sweeps can be attributed to adaptations occurring through epistatic, multi-locus architecture or introgression.