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

Abstract

Negative frequency-dependent selection (NFDS) is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa. We fine-map one locus associated with D. magna resistance to P. ramosa and genetically characterize two haplotypes of the Pasteuria resistance (PR-) locus using de novo genome and transcriptome sequencing. Sequence comparison of PR-locus haplotypes finds dramatic structural polymorphisms between PR-locus haplotypes including a large portion of each haplotype being composed of non-homologous sequences resulting in haplotypes differing in size by 66 kb. The high divergence of PR-locus haplotypes suggest a history of multiple, diverse and repeated instances of structural mutation events and restricted recombination. Annotation of the haplotypes reveals striking differences in gene content. In particular, a group of glycosyltransferase genes that is present in the susceptible but absent in the resistant haplotype. Moreover, in natural populations, we find that the PR-locus polymorphism is associated with variation in resistance to different P. ramosa genotypes, pointing to the PR-locus polymorphism as being responsible for the matching-allele interactions that have been previously described for this system. Our results conclusively identify a genetic basis for the matching-allele interaction observed in a coevolving host-parasite system and provide a first insight into its molecular basis.

Author summary

Negative frequency-dependent selection, whereby common genotypes are disfavored, resulting in cyclic change of gene frequencies and maintenance of genetic diversity in host and parasite populations, is one the mechanisms predicted to drive host-parasite coevolution. Specific matching-allele interactions between hosts and parasites are a mechanism predicted to underpin this mode of selection. In spite of in depth research, little is known about the genetic basis of such matching-allele interactions and few empirical examples have been described. Recent research has suggested that the Daphnia- Pasteuria host-parasite system follows a model of negative frequency-dependent selection. We map a Daphnia magna locus of resistance to Pasteuria ramosa. We use next-generation genome and transcriptome sequencing to characterize resistant and susceptible haplotypes of the resistance locus. We find large-scale structural polymorphism between resistance locus haplotypes and we find evidence that gene conversion, segment duplication and restricted homologous recombination contribute to produce the observed polymorphisms. We analyse natural populations and find that the resistance locus structural polymorphisms reproduce the matching-allele interactions predicted for the Daphnia-Pasteuria system. This work presents rare and conclusive evidence of the genetic basis of matching-allele interactions in host-parasite systems while opening research avenues to find the underlying molecular mechanisms.