QTL study reveals candidate genes underlying host resistance in a Red Queen model system

Author summaryIdentifying the genes under selection is often a necessary step toward understanding the processes that drive evolution. In the case of coevolving hosts and parasites, the host genes under selection are those that confer resistance to the parasite. Here, we aim to identify genes conferring resistance in a coevolving host-parasite system. We map a newly discovered resistance locus to a region adjacent to a previously described resistance supergene, and we validate the locus with additional genetic crosses. By comparing the genes present in resistant versus susceptible hosts and by analyzing gene expression data, we identify eight biological candidates. One of the top candidates represents a newly identified gene family that is only found in closely related species and is duplicated in several areas in the genome, and another top candidate strengthens a working hypothesis that resistance might depend on sugar molecules. This work broadens our perspective on the complexity and diversity of resistance loci in this host-parasite system, and it pinpoints intriguing candidates that will be tested in future gene knock-out experiments. Follow-up population genetic studies will help us better understand how parasites coevolve with their hosts in natural populations. Specific interactions of host and parasite genotypes can lead to balancing selection, maintaining genetic diversity within populations. In order to understand the drivers of such specific coevolution, it is necessary to identify the molecular underpinnings of these genotypic interactions. Here, we investigate the genetic basis of resistance in the crustacean host, Daphnia magna, to attachment and subsequent infection by the bacterial parasite, Pasteuria ramosa. We discover a single locus with Mendelian segregation (3:1 ratio) with resistance being dominant, which we call the F locus. We use QTL analysis and fine mapping to localize the F locus to a 28.8-kb region in the host genome, adjacent to a known resistance supergene. We compare the 28.8-kb region in the two QTL parents to identify differences between host genotypes that are resistant versus susceptible to attachment and infection by the parasite. We identify 13 genes in the region, from which we highlight eight biological candidates for the F locus, based on presence/absence polymorphisms and differential gene expression. The top candidates include a fucosyltransferase gene that is only present in one of the two QTL parents, as well as several Cladoceran-specific genes belonging to a large family that is represented in multiple locations of the host genome. Fucosyltransferases have been linked to resistance in previous studies of Daphnia-Pasteuria and other host-parasite systems, suggesting that P. ramosa spore attachment could be mediated by changes in glycan structures on D. magna cuticle proteins. The Cladoceran-specific candidate genes suggest a resistance strategy that relies on gene duplication. Our results add a new locus to a growing genetic model of resistance in the D. magna-P. ramosa system. The identified candidate genes will be used in future functional genetic studies, with the ultimate aim to test for cycles of allele frequencies in natural populations.

Automated summary

Identifying genes that confer resistance in a coevolving host-parasite system is important for understanding evolution. By comparing resistant and susceptible hosts, analyzing gene expression data, and performing genetic crosses, this study identifies eight candidate genes that may confer resistance to parasites. This research expands our understanding of resistance loci and provides candidates to be tested in future experiments.