Multigene families are at the core of immune system complexity, shaping how organisms sense, respond to, and remember infection. Gene duplication, diversification, domain shuffling, and gene loss have collectively generated the extraordinary repertoires of immune receptors, cytokines, effectors, and regulators observed across living organisms. Their evolution is often described as a “birth-and-death” process, in which new genes arise by duplication while others are lost or pseudogenized under fluctuating selection imposed by pathogens, microbiota, and ecological or reproductive pressures. The recent expansion of chromosome-level genomes, population-scale sequencing, and functional and structural immunology now makes it possible to examine these multigene families comparatively across deep evolutionary time and diverse taxa. This Research Topic will explore how gene gain and loss, diversification, convergence, constraint, and co-option collectively “shape immunity” by sculpting the architecture and function of immune multigene families.

The goal of this Research Topic is to build an integrated framework for understanding how immune multigene families evolve and how this evolution shapes immune function. We aim to move beyond case-by-case descriptions of individual loci to comparative, mechanistic insight across lineages, cell types, and ecological contexts. By bringing together evolutionary genomics, structural and functional immunology, and systems-level analyses, this Special Issue will ask why some lineages undergo dramatic expansions of receptors, cytokines, or effector molecules while others retain compact, constrained repertoires, and how copy number changes, structural rearrangements, or pseudogenization influence infection outcomes, immune regulation, and pathology. We particularly encourage studies that harness new resources, including chromosome-level and pangenome assemblies, population-scale datasets, single-cell and repertoire sequencing, and innovative computational or experimental tools, to connect gene family dynamics with concrete immune phenotypes and to link molecular and genomic architecture to organismal and population-level immunity.

This Research Topic will bring together contributions that dissect how immune multigene families originate, diversify, and are functionally shaped across organisms and contexts.

We encourage integrative studies that connect genomic architecture to immune phenotypes at the cellular, organismal, and population levels.

We welcome the submission of Original Research, Review, Mini Review, and Perspective articles on themes including, but not limited to:

• the emergence, expansion, and contraction of key immune gene families (such as antigen receptors and MHC)

• the organization of immune loci in genomes and pangenomes

• host-pathogen and host-microbiota coevolution

• the impact of copy number and sequence variation on effector function

• single-cell and spatial omics mapping of multigene families

• convergent evolution of analogous immune solutions

Are you interested in contributing a manuscript to this Research Topic?

Shaping Immunity: Evolutionary Dynamics of Immune Multigene Families