# Macroevolutionary changes in gene expression response to an immune stimulus across the diversity of fishes

## TL;DR

This study shows that while the immune response to a stimulus is similar in many fish species, the genes involved vary widely, suggesting the need for diverse models to understand immunity.

## Contribution

The study reveals macroevolutionary flexibility in the gene regulatory architecture of immune responses across ray-finned fishes.

## Key findings

- The fibrosis response to an immune challenge is conserved across 14 fish species.
- Transcriptomic responses to the immune stimulus are inconsistent across species.
- Few gene orthogroups show consistent differential expression across all species.

## Abstract

Our understanding of the vertebrate immune system is dominated by a few model organisms such as mice. This use of a few model systems is reasonable if major features of the immune systems evolve slowly and are conserved across most vertebrates, but may be problematic if there is substantial macroevolutionary change in immune responses. Here, we present a test of the macroevolutionary stability, across 14 species of ray-finned fishes, of the transcriptomic response to a standardized immune challenge. Intraperitoneal injection of an immune adjuvant (alum) induces a fibrosis response in nearly all jawed fishes, which in some species contributes to anti-helminth protection. Despite this conserved phenotypic response, the underlying transcriptomic response is highly inconsistent across species. Although many gene orthogroups exhibit differential expression between saline versus alum-injected fish in at least one species, few orthogroups exhibit consistent differential expression across species. This result suggests that although the phenotypic response to alum (fibrosis) is highly conserved, the underlying gene regulatory architecture is very flexible and cannot readily be extrapolated from any one species to fishes (or vertebrates) more broadly. The vertebrate immune response is remarkably changeable over macroevolutionary time, requiring a diversity of model organisms to describe effectively.