The Red Queen lives: Epistasis between linked resistance loci

Abstract

A popular theory explaining the maintenance of genetic recombination (sex) is the Red Queen Theory. This theory revolves around the idea that time-lagged negative frequency-dependent selection by parasites favors rare host genotypes generated through recombination. Although the Red Queen has been studied for decades, one of its key assumptions has remained unsupported. The signature host-parasite specificity underlying the Red Queen, where infection depends on a match between host and parasite genotypes, relies on epistasis between linked resistance loci for which no empirical evidence exists. We performed 13 genetic crosses and tested over 7000 Daphnia magna genotypes for resistance to two strains of the bacterial pathogen Pasteuria ramosa. Results reveal the presence of strong epistasis between three closely linked resistance loci. One locus masks the expression of the other two, while these two interact to produce a single resistance phenotype. Changing a single allele on one of these interacting loci can reverse resistance against the tested parasites. Such a genetic mechanism is consistent with host and parasite specificity assumed by the Red Queen Theory. These results thus provide evidence for a fundamental assumption of this theory and provide a genetic basis for understanding the Red Queen dynamics in the Daphnia-Pasteuria system.

The genetic basis of resistance and matching-allele interactions of a host-parasite system: The Daphnia magna-Pasteuria ramosa model

“…Importantly, spore attachment is genetically determined and fully consistent with infection success, i.e. resistant host genotypes prevent spore attachment whereas attachment is successful in susceptible host genotypes [19–22]. Here we use the terms resistance and susceptibility to refer to both spore attachment and overall infection.…”

Higher rates of sex evolve during adaptation to more complex environments

“…Numerous hypotheses have been proposed to explain how the benefits of sex may outweigh its costs (see refs. 3 and 5 for reviews) and, although studies have provided tests of core assumptions (6,7) or found evidence consistent with theory (8)(9)(10), direct experimental evidence of sex evolving within populations remains rare (but see refs. 11 and 12).…”

Evidence of epistasis provides further support to the Red Queen theory of host-parasite coevolution

“…that this genetic host-parasite match involves several linked resistance loci, remained unsupported so far. Metzger and coauthors [1] now provide empirical support for it. Daphnia magna can reproduce both sexually and clonally and their well-studied interaction with Pasteuria ramosa makes them an excellent model system to investigate the genetics of host resistance.…”

“…D. magna hosts were found to be either resistant (complete lack of attachment of parasite spores to the host's foregut) or susceptible (full attachment). In this study the authors carried out an elegant Mendelian genetic investigation by performing multiple crosses between four host genotypes differing in their resistance to two different parasite isolates [1]. Their results show that resistance of D. magna to each of the two P. ramosa isolates relies on Mendelian inheritance at two loci that are linked (A and B), each of them having two alleles with dominant resistance; furthermore resistance to one parasite isolate confers susceptibility to the other.…”