The pig family is an unusually valuable model for studying immune evolution. Suids occupy a remarkable range of ecological niches, from the forests and farms where domestic pigs live to the arid savannas inhabited by warthogs and bushpigs. Alongside this ecological breadth comes wide variation in disease susceptibility. African wild suids can tolerate infections that devastate domestic pigs, and understanding the genetic basis of such differences has long been a goal for evolutionary biologists and veterinary researchers alike. Yet before this study, no systematic cross-species survey of immune gene variation had been carried out across the family.

To build their dataset, the team first compiled a high-confidence set of 1,946 conserved mammalian immune-related genes. These genes, drawn from established annotation frameworks, span the major arms of the immune system, including innate recognition, inflammatory signaling, and adaptive responses. The researchers then mapped whole-genome sequencing reads from the 12 suid species against these genes, calling single-nucleotide variants and small insertions and deletions with careful quality filtering. Stringent filters based on metrics such as read depth, strand bias, and variant quality ensured that the variants used in downstream analyses were unlikely to be sequencing artifacts.

From this foundation, the team searched for what they term critical variants: mutations predicted to cause the gain or loss of start or stop codons, frameshifts, or disruptions of splice sites. Such mutations can profoundly alter protein function. Across the 12 species, the analysis identified 51 genes carrying 62 lineage-specifically fixed critical variants, meaning the damaging allele is present in all members of one lineage while absent from the others. Among these, 21 events were classified as putative loss-of-function mutations, disrupting more than half of the protein-coding sequence of the affected gene.

One of the most notable findings concerns the interleukin-1 gene family, a cluster of genes central to inflammation and innate immunity. The study found evidence of progressive degeneration within this family across suid evolution, with different lineages showing different degrees of decay. Degenerating gene families are a well-known feature of genome evolution, but their occurrence in a family of genes as immunologically important as the interleukin-1 cluster suggests that some inflammatory functions may have been relaxed or reshaped in particular suid lineages, potentially altering how these animals mount fever and inflammatory responses to infection.

African suids emerged as a particularly distinctive case. Warthogs, bushpigs, and forest hogs showed unique evolutionary signatures in innate immune and inflammatory pathways, including the apparent inactivation of the CD177 gene. CD177 encodes a protein expressed on a subset of neutrophils, the white blood cells that form the first line of defense against bacterial and fungal pathogens, and it has been implicated in inflammatory regulation in other mammals. Its inactivation in African suids hints at a rewiring of neutrophil biology in these species, although the precise functional consequences will require experimental follow-up.

In contrast, the Sus lineage, which includes domestic pigs and wild boars, harbored fewer disruptive variants than the other suid lineages. Instead, it showed strong evidence of positive selection in genes associated with cytokine interactions and responses to infectious disease. Positive selection leaves a statistical footprint in coding sequences, detectable when the ratio of nonsynonymous to synonymous substitutions exceeds what neutral evolution would predict. In the Sus lineage, this signal concentrated in genes that mediate communication between immune cells, suggesting that the ancestors of pigs and boars experienced intense pathogen-driven pressure on the molecular machinery of immune signaling.

The recurrent appearance of immune gene inactivation across multiple, independent lineages is one of the study’s most thought-provoking results. Gene loss in the immune system can arise through genetic drift, particularly when a gene’s function becomes dispensable, but it can also be driven by positive selection, for example when losing a receptor deprives a pathogen of its entry point. The authors argue that both forces have shaped the suid immunome, with drift and selection combining in different measures across lineages to produce the diversity of immune gene repertoires observed today. Disentangling these contributions remains a central challenge in evolutionary immunology.

These findings carry practical implications beyond evolutionary theory. Domestic pigs are economically vital livestock and, at the same time, a reservoir and amplifier of pathogens with serious veterinary and public health consequences, including African swine fever virus, porcine reproductive and respiratory syndrome virus, and foot-and-mouth disease virus. African wild suids, which can host African swine fever virus without severe disease, represent natural experiments in tolerance that could illuminate resistance mechanisms. By pinpointing the immune genes that have been disrupted or positively selected in specific lineages, the study provides a shortlist of candidate loci for functional studies aimed at improving disease resistance and immune robustness in pigs.

The study also demonstrates the power of telomere-to-telomere era genomic resources and improved annotations when applied across non-model species. As reference genomes for wild suids continue to improve, the researchers expect the catalogue of lineage-specific immune variants to grow in resolution. For now, the work offers the first panoramic view of immune gene evolution across the pig family, revealing that even closely related mammals can take sharply divergent routes in building and pruning their immune systems, and that some of those routes may hold the keys to breeding healthier livestock.

Subject of Research: Comparative immunogenomics of immune gene evolution, loss-of-function variation, and positive selection across Suidae species

Article Title: Comparative immunogenomics of Suidae reveals lineage-specific immune gene disruption and positive selection

Article References: Shin, J. Y., Ahn, B., Kang, M., Dinka, H., Lee, J., Choi, M.-K., & Park, C. (2026). Comparative immunogenomics of Suidae reveals lineage-specific immune gene disruption and positive selection. BMC Genomics. https://doi.org/10.1186/s12864-026-13424-0

Image Credits: AI Generated

DOI: 10.1186/s12864-026-13424-0

Keywords: Suidae, immunogenomics, comparative genomics, loss-of-function mutation, positive selection, IL-1 gene family, CD177, African swine fever, innate immunity, host-pathogen coevolution, whole-genome sequencing, disease resistance