Petrohilos Cleopatra, Peel Emma, Silver Luke W, Belov Katherine, Hogg Carolyn J
School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, Australia.
Australian Research Council Centre of Excellence for Innovations in Peptide & Protein Science, The University of Sydney, Sydney, NSW, Australia.
Immunogenetics. 2025 Jan 8;77(1):11. doi: 10.1007/s00251-024-01368-2.
Characterising functional diversity is a vital element to understanding a species' immune function, yet many immunogenetic studies in non-model organisms tend to focus on only one or two gene families such as the major histocompatibility complex (MHC) or toll-like receptors (TLR). Another interesting component of the eukaryotic innate immune system is the antimicrobial peptides (AMPs). The two major groups of mammalian AMPs are cathelicidins and defensins, with the former having undergone species-specific expansions in marsupials. Here, we utilised data from 418 koala whole genomes to undertake the first comprehensive analysis of AMP diversity across a mammalian wildlife species' range. Overall, allelic diversity was lower than other immune gene families such as MHC, suggesting that AMPs are more conserved, although balancing selection was observed in PhciDEFB12. Some non-synonymous SNPs in the active peptide are predicted to change AMP function through stop gains, change in structure, and increase in peptide charge. Copy number variants (CNVs) were observed in two defensins and one cathelicidin. Interestingly, the most common CNV was the duplication of PhciCATH5, a cathelicidin with activity against chlamydia, which was more common in the southern part of the species range than the north. AMP copy number is correlated with expression levels, so we hypothesise that there is a selective pressure from chlamydia for duplications in PhciCATH5. Future studies should use phenotypic metadata to assess the functional impacts of this gene duplication.
表征功能多样性是理解物种免疫功能的关键要素，然而许多针对非模式生物的免疫遗传学研究往往仅聚焦于一两个基因家族，如主要组织相容性复合体（MHC）或Toll样受体（TLR）。真核生物先天免疫系统的另一个有趣组成部分是抗菌肽（AMP）。哺乳动物的AMP主要分为两类，即cathelicidin和防御素，其中前者在有袋动物中经历了物种特异性的扩增。在此，我们利用来自418个考拉全基因组的数据，首次对一种哺乳动物野生动物物种范围内的AMP多样性进行了全面分析。总体而言，等位基因多样性低于MHC等其他免疫基因家族，这表明AMP更为保守，尽管在PhciDEFB12中观察到了平衡选择。活性肽中的一些非同义单核苷酸多态性（SNP）预计会通过产生终止密码子、结构变化和肽电荷增加来改变AMP的功能。在两种防御素和一种cathelicidin中观察到了拷贝数变异（CNV）。有趣的是，最常见的CNV是PhciCATH5的重复，PhciCATH5是一种对衣原体有活性的cathelicidin，在该物种分布范围的南部比北部更为常见。AMP拷贝数与表达水平相关，因此我们推测衣原体对PhciCATH5的重复存在选择压力。未来的研究应使用表型元数据来评估这种基因重复的功能影响。
