Evolution of immunity to cestode parasites is a pyrrhic victory
Authors: Jesse Weber 1; Natalie Steinel 2; Foen Peng 3; Kum Chuan Shim 4; Brian Lohman 5; Lauren Fuess 6; Stephen De Lisle 7; Daniel Bolnick 8
Affiliations: 1) University of Wisconsin-Madison, Madison, WI; 2) University of Massachusetts Lowell, Lowell, MA; 3) Haverford College, Haverford, PA; 4) University of Texas at Austin, Austin, TX; 5) Eccles Institute of Human Genetics, Salt Lake City, UT; 6) Texas State University, San Marcos, TX; 7) Lund University, Lund, Sweeden; 8) University of Connecticut, Storrs, CT
Keywords: Ecological & conservation genetics
Parasites impose fitness costs on their hosts. Biologists therefore tend to assume that natural selection favors infection-resistant hosts. Yet, when the immune response itself is costly, theory suggests selection may instead favor loss of resistance. Immune costs are rarely documented in nature, and there are few examples of adaptive loss of resistance. Here, we show that threespine stickleback fish (Gasterosteus aculeatus) have repeatedly gained immunity to a tapeworm parasite, during their replicated colonization of freshwater in the past 12,000 years. Yet, some freshwater fish populations have more complex and effective immunity than others. We identify the phenotypic and genetic basis of this recently-evolved variation in immunity. In particular, tapeworm infection stimulates inflammation and extensive fibrosis throughout the body cavity, which in turn contributes to suppression of parasite growth (in both lab and wild fish), and can kill the tapeworm. However, this fibrosis response is costly, drastically reducing female and male reproductive success (in both lab and wild fish). Consistent with these costs, our quantitative genetic, population genomic, transcriptomic, and phylogenetic analyses all suggest that, in multiple freshwater populations that currently lack fibrosis and tolerate tapeworm growth, selection acted to favor the loss of this costly immune response. We also highlight several striking genetic changes that likely underlie these gains and losses of immunity. These results are unique in that we show the repeated gain and loss of immune adaptations across closely related conspecific populations. Moreover, our findings showcase the biomedical relevance of exploring the genetics of infection variation in wild vertebrates. Fibrosis is a major pathology in humans, and we show that stickleback contain naturally evolved genetic variation in pro- and anti-fibrotic pathways, providing a new model system to better understand fibrosis and inflammation in our own species.