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

Understanding the evolutionary dynamics of immune-related (IR) genes among closely related species provides key insights into lineage-specific adaptations to pathogens. The family Suidae is a powerful model for investigating immune gene evolution owing to its broad ecological diversity and varying susceptibility to infectious diseases. We compiled a high-confidence dataset of 1946 conserved mammalian IR genes and analyzed whole-genome sequencing data from 72 individuals representing 12 Suidae species. Comparative genomic analyses revealed distinct lineage-specific patterns of genetic variation, identifying 51 genes with 62 lineage-specifically fixed critical variants (predicted to cause start- or stop-codon gain or loss, frameshift, or splice-site variants), including 21 putative loss-of-function events (disrupting > 50% of the coding sequence). Evidence of progressive degeneration within the IL-1 gene family was also observed. African suids exhibited unique evolutionary signatures in innate immune and inflammatory pathways, notably including CD177 inactivation. Interestingly, the Sus lineage harbored fewer disruptive variants than other suid lineages and showed strong evidence of positive selection in genes associated with cytokine interactions and responses to infectious disease. To our knowledge, our findings provide the first comprehensive overview of immune gene variation across Suidae and reveal lineage-specific evolutionary trajectories underlying immune system diversity. The recurrent occurrence of immune gene inactivation across multiple lineages highlights combined roles of genetic drift and positive selection in shaping the suid immunome. This study offers important insights into host–pathogen coevolution in suids, advancing research on disease resistance and immune robustness in suid species.