Lineage-specific protein repeat expansions and contractions reveal malleable regions of immune genes

Functional diversification, a higher evolutionary rate, and intense positive selection help a limited number of immune genes interact with many pathogens. Repeats in protein-coding regions are a well-known source of functional diversification, adaptive variation, and evolutionary novelty in a short time. Repeats play a crucial role in biochemical functions like functional diversification of transcription regulation, protein kinases, cell adhesion, signaling pathways, morphogenesis, DNA repair, recombination, and RNA processing. Repeat length variation can change the associated protein's interaction, efficacy, and overall protein network. Repeats have an intrinsic unstable nature and can potentially evolve rapidly and expedite the acquisition of complex phenotypic traits and functions. Because of their ability to generate rapid, adaptive variations over short evolutionary distances, repeats are considered "tuning knobs." Repeat length variation in specific genes, like RUNX2 and ALX4, is associated with morphological and physiological changes across vertebrates. Here we study repeat length variation as a potent source of species-specific immune diversification across several clades of tetrapods. Moreover, we provide a clade-wise comprehensive list of immune genes with repeat types for future studies of morphological/evolutionary changes within species groups. We observe significant repeat length variation of FASLG and C1QC in Rodentia and Primates' contrasting species groups, respectively.

有限的免疫基因可通过功能分化、更高的进化速率与强烈的正向选择，与众多病原体产生相互作用。蛋白质编码区中的重复序列是已知的、可在短时间内催生功能分化、适应性变异与进化新性状的重要来源。
重复序列在多项生化功能中扮演关键角色，诸如转录调控、蛋白激酶（Protein kinases）活性、细胞黏附、信号通路、形态发生、DNA修复、重组及RNA加工等过程中的功能分化。重复序列的长度变异可改变其所关联蛋白的相互作用、功能效力以及整体蛋白质互作网络。
重复序列具有固有不稳定性，能够快速进化并加速复杂表型性状与功能的获得。由于其可在较短进化跨度内快速产生适应性变异，重复序列被称为「调控旋钮（tuning knobs）」。
特定基因（如RUNX2与ALX4）中的重复序列长度变异，与脊椎动物类群广泛存在的形态与生理变化密切相关。本研究以四足动物（tetrapods）多个演化支系为研究对象，探究重复序列长度变异作为物种特异性免疫分化的重要来源。
此外，本研究还提供了一份按演化支系分类的免疫基因与重复类型综合列表，以供后续物种类群内形态与进化变化的相关研究使用。我们分别在啮齿目（Rodentia）与灵长目（Primates）的对比物种类群中，观测到FASLG与C1QC基因存在显著的重复序列长度变异。