Changes in gene regulation are associated with the evolution of resistance to a novel parasite

Host-parasite interactions are ubiquitous and are important drivers of host diversification and evolution. In particular, host immune systems are frequent targets of parasite-driven selection. The resulting rapid evolution of immune genes is usually framed as an ongoing 'arms race' between a co-evolving pair of host and parasite species. However, immune evolution may often be driven by the acquisition of a new and unfamiliar parasite. For instance, when marine populations of threespine stickleback (Gasterosteus aculeatus) colonized freshwater lakes approximately 12,000 years ago, they encountered the freshwater-restricted cestode Schistocephalus solidus and evolved resistance.

We compared the transcriptomic responses of lab-reared sticklebacks from three populations of stickleback with varying cestode susceptibilities when exposed to several immune stimuli (alum, cestode protein, or a control injection).

The resulting changes in expression reveal strong evidence of shared and population-specific responses during the evolution of defense against a new parasite. Our investigation highlights the roles of several key immunological processes in underlying a general physiological response to tissue damage (fibrosis) and the importance of regulating fibrosis as a necessary step for its co-option into defense against S. solidus tapeworms. Furthermore, we highlighted changes in the expression of fibrosis-associated genes, which facilitate faster and more targeted deployment of this defense mechanism against parasites. Fish from the most fibrosis-prone population exhibited constitutively higher expression of fibrosis-associated genes and stronger downregulation of these genes after an initial stimulus from injected cestode proteins.

Our results provide strong evidence that changes in gene regulation and increased negative feedback to mitigate immunopathology are essential steps in the evolutionary co-option of an existing pathway to defend against a new parasite infection.