Parallel evolution of viral resistance in two Caenorhabditis species  through repeated mutation of a GT92 glycosyltransferase gene
Host-pathogen interactions often evolve rapidly within species, thus allowing the identification of ecological interaction factors using natural genetic variation. We previously identified several RNA viruses related to nodaviruses that naturally infect the nematodes C. elegans and C. briggsae, in a species-specific fashion. Prior assays of infections of diverse C. elegans and C. briggsae wild strains by their respective viruses demonstrated ample variation in sensitivity, which we leverage here to idenitfy causal polymorphisms. In C. elegans, we had found by genome-wide association mapping that a deletion polymorphism in drh-1, the RIG-I homolog, explained a significant part of the intraspecific variation in Orsay virus replication level. Strikingly, the wild strain MY10, despite carrying the drh-1 deletion, was among the most resistant strains. Here, using quantitative genetic analysis of crosses of MY10 with permissive strains, we found that a major locus on chromosome V underlies MY10's resistance. We fine-mapped the locus using spontaneous and CRISPR-Cas9 induced recombination and demonstrated by precise genome editing that a rare non-synonymous polymorphism (P182L) in the gtnt-1 gene in MY10 causes resistance to viral infection. The gtnt-1 gene encodes a putative glycosyltransferase of the GT92 family. Other wild C. elegans strains carrying putative null gtnt-1 alleles are also resistant to the virus. Moreover, repeated reduction-of-function alleles of the Cbr-gtnt-1 ortholog affect virus infection in C. briggsae. In conclusion, we found repeated evolution in the two species of rare reduction-of-function alleles of the gtnt-1 orthologs, which do not fix but repeatedly lead to viral resistance.