TY - JOUR T1 - Patterns and Causes of Signed Linkage Disequilibria in Flies and Plants JF - bioRxiv DO - 10.1101/2020.11.25.399030 SP - 2020.11.25.399030 AU - George Sandler AU - Stephen I. Wright AU - Aneil F. Agrawal Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/05/03/2020.11.25.399030.abstract N2 - Most empirical studies of linkage disequilibrium (LD) study its magnitude, ignoring its sign. Here, we examine patterns of signed LD in two population genomic datasets, one from Capsella grandiflora and one from Drosophila melanogaster. We consider how processes such as drift, admixture, Hill-Robertson interference, and epistasis may contribute to these patterns. We report that most types of mutations exhibit positive LD, particularly, if they are predicted to be less deleterious. We show with simulations that this pattern arises easily in a model of admixture or distance biased mating, and that genome-wide differences across site types are generally expected due to differences in the strength of purifying selection even in the absence of epistasis. We further explore how signed LD decays on a finer scale, showing that loss of function mutations exhibit particularly positive LD across short distances, a pattern consistent with intragenic antagonistic epistasis. Controlling for genomic distance, signed LD in C. grandiflora decays faster within genes, compared to between genes, likely a by-product of frequent recombination in gene promoters known to occur in plant genomes. Finally, we use information from published biological networks to explore whether there is evidence for negative synergistic epistasis between interacting radical missense mutations. In D. melanogaster networks, we find a modest but significant enrichment of negative LD, consistent with the possibility of intra-network negative synergistic epistasis.Competing Interest StatementThe authors have declared no competing interest. ER -