A gene with a thousand alleles: the HYPer-variable effectors of plant-parasitic nematodes

Pathogens are engaged in a fierce evolutionary arms race with their host. The genes at the forefront of the engagement between kingdoms, including effectors and immune receptors, are part of diverse and highly mutable gene families. Even in this context, we discovered unprecedented variation in the HYPer-variable (HYP) effectors of plant-parasitic nematodes. We discovered single effector gene loci that can harbour potentially thousands of allelic variants. These alleles vary in the number, but principally in the organisation, of motifs within a central Hyper Variable Domain (HVD). Using targeted long-read sequencing, we dramatically expand the HYP repertoire of two plant-parasitic nematodes, Globodera pallida and G. rostochiensis, such that we can define distinct sets of species-specific “rules” underlying the apparently flawless genetic rearrangements. Finally, by analysing the HYP complement of 68 individual nematodes we made the unexpected finding that despite the huge number of alleles, most individuals are homozygous. Taken together, these data point to a novel mechanism of programmed genetic variation, termed HVD-editing, where alterations are locus-specific, strictly governed by rules, and can theoretically produce thousands of variants without errors.