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Immune systems pose fascinating puzzles for evolutionary biologists. They feature some of the most polymorphic genes and reflect the strongest natural selection known. Evolution of immune systems plays a key role in host–parasite interactions, speciation, and eco-evolutionary dynamics that have community- and ecosystem-wide consequences. Conversely, evolutionary perspectives enrich our understanding of immunology, revealing macroevolutionary origins of key immune traits, their function in wild populations as opposed to sterile lab settings, and trade-offs that constrain immune adaptation. Here, we review key themes in the fast-growing interdisciplinary field of evolutionary immunology, focusing on multicellular animals. We describe macroevolution of immune functions, evidence of contemporary selection on immune genes, and the underlying theory seeking to explain this selection at multiple biological scales. We identify major open questions and opportunities in the field today. Foremost among these is the challenge of accurately and appropriately measuring relevant immune traits in wild and nonmodel organisms, which is necessary to understand their evolution in natural settings. A second challenge is to describe how diverse communities of symbionts impose selection on the highly multivariate and pleiotropic immune system.more » « lessFree, publicly-accessible full text available May 6, 2026
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