Thanks very much! We took a lot of inspiration from the stickleback work you all have been doing, of course.

If you have questions, comments, ideas, please get in touch! I love these topics and am always eager to chat about them with others, or evangelize, or learn!

Many thanks to @jennytung.bsky.social for writing this with me – the vague forms of these ideas have been rattling around in my head for a while, but she did a remarkable job using her own expertise and ideas to help me refine the concepts and express them in a clear format.

But we hope that our paper can help anyone working on immune system evolution, when thinking about their hypotheses, the methods they use to test them, and the implications of their results for the broader field of inquiry.

There’s a wealth of great recent literature out there on evolutionary immunology (e.g., this review from @danielbolnick.bsky.social @laurenfuess.bsky.social @grahammunology.bsky.social @nataliesteinel.bsky.social
and others not here: doi.org/10.1146/annu...)

We also take a brief detour into genetic architecture, on the heels of findings from both theoretical evolutionary genetics and ecological immunology suggesting that differing architectures (in polygenicity or pleiotropy) may have substantive implications for when and how immune defenses can evolve.

We briefly discuss how the overarching aspects of immune strategy hypothesized in immune theory may be encoded in phenotypes and in the genome, an ongoing challenge for translating between these two approaches.

For each question, we highlight how hypotheses from ecological immunology might be effectively explored if methods and techniques from evolutionary genetics are applied. We also highlight some recent papers that exemplify such a fusion's value (e.g. www.science.org/doi/full/10....).

3. How do immune differences across species originate? Many taxa display unusual immunological phenotypes (e.g., bats and constitutive cytokine expression) hypothesized to spring from their particular biology. Can we see signatures of this with broad phylogenetic analyses?

2. What constrains immune evolution? For example, resource-based trade-offs between immunity and life history traits are a common prediction. But are there genetic correlations in these traits in nature, such that these relationships can actually respond to selection?

1. When and where should immune traits be targeted by natural selection? What should we actually expect the signatures of selection to look like – which traits, which genes – and how is that modulated by the ecology and demography of the host?

In our review, we highlight three key questions in the evolution of immune systems, and we discuss how evolutionary geneticists and ecoimmunologists can fuse their approaches for deeper insights.

Making progress here requires thinking through our hypotheses clearly, understanding their assumptions and implications, and being granular prediction, actively drawing on the insights into immune defenses from a variety of contexts and systems. Combining frameworks will encourage that rigor.

Evolutionary genetics identifies particular loci and traits that may (or may not) be responding to selection. But it can leaves us uncertain as to why a particular evolutionary path has been taken, what the selective force is, and even sometimes what is the advantage that evolved.

Ecological immunology explores the immune system from the perspective of the whole organism, investigating resource allocation, life history, and ideal immune strategies. But this perspective can be vague on the expected targets of selection and underlying evolutionary processes.

We here focus on ecological immunology and evolutionary genetics, which we think have a great deal to offer each other in the study of immune variation and evolution (and which we plan to combine ourselves in the future...)

However, there are many, many open questions in the field, and while researchers have taken many different approaches, work in different fields often takes place in parallel, without effective communication or sharing of insights.

Parasites are a key force of selection in natural populations, and immune genes are “hotspots” of positive selection across the tree of life. Why immune phenotypes vary in nature, and how they evolve, has been a fertile topic of research for decades.