Cheng Yuanyuan, Prickett Michael Dennis, Gutowska Weronika, Kuo Richard, Belov Katherine, Burt David W
RMC Gunn Building B19, Faculty of Veterinary Science, University of Sydney, Camperdown, 2006, NSW, Australia.
Dipartimento di Scienze della Vita-Edif. C11, Università di Trieste, Via Licio Giorgieri 1, 34127, Trieste, Italy.
BMC Evol Biol. 2015 Sep 15;15:188. doi: 10.1186/s12862-015-0465-3.
β-defensins and cathelicidins are two families of cationic antimicrobial peptides (AMPs) with a broad range of antimicrobial activities that are key components of the innate immune system. Due to their important roles in host defense against rapidly evolving pathogens, the two gene families provide an ideal system for studying adaptive gene evolution. In this study we performed phylogenetic and selection analyses on β-defensins and cathelicidins from 53 avian species representing 32 orders to examine the evolutionary dynamics of these peptides in birds.
Avian β-defensins are found in a gene cluster consisting of 13 subfamiles. Nine of these are conserved as one to one orthologs in all birds, while the others (AvBD1, AvBD3, AvBD7 and AvBD14) are more subject to gene duplication or pseudogenisation events in specific avian lineages. Avian cathelicidins are found in a gene cluster consisting of three subfamilies with species-specific duplications and gene loss. Evidence suggested that the propiece and mature peptide domains of avian cathelicidins are possibly co-evolving in such a way that the cationicity of the mature peptide is partially neutralised by the negative charge of the propiece prior to peptide secretion (further evidence obtained by repeating the analyses on primate cathelicidins). Negative selection (overall mean dN < dS) was detected in most of the gene domains examined, conserving certain amino acid residues that may be functionally crucial for the avian β-defensins and cathelicidins, while episodic positive selection was also involved in driving the diversification of specific codon sites of certain AMPs in avian evolutionary history. These findings have greatly improved our understanding of the molecular evolution of avian AMPs and will be useful to understand their role in the avian innate immune response. Additionally, the large dataset of β-defensin and cathelicidin peptides may also provide a valuable resource for translational research and development of novel antimicrobial agents in the future.
β-防御素和cathelicidin是两类阳离子抗菌肽(AMPs),具有广泛的抗菌活性,是先天免疫系统的关键组成部分。由于它们在宿主抵御快速进化病原体方面的重要作用,这两个基因家族为研究适应性基因进化提供了一个理想的系统。在本研究中,我们对代表32个目的53种鸟类的β-防御素和cathelicidin进行了系统发育和选择分析,以研究这些肽在鸟类中的进化动态。
鸟类β-防御素存在于一个由13个亚家族组成的基因簇中。其中9个在所有鸟类中作为一对一的直系同源物保守存在,而其他的(AvBD1、AvBD3、AvBD7和AvBD14)在特定鸟类谱系中更容易发生基因复制或假基因化事件。鸟类cathelicidin存在于一个由三个亚家族组成的基因簇中,具有物种特异性的复制和基因丢失。有证据表明,鸟类cathelicidin的前肽和成熟肽结构域可能以这样一种方式共同进化,即成熟肽的阳离子性在肽分泌之前被前肽的负电荷部分中和(通过对灵长类动物cathelicidin重复分析获得了进一步证据)。在大多数检测的基因结构域中检测到负选择(总体平均dN < dS),保留了某些可能对鸟类β-防御素和cathelicidin功能至关重要的氨基酸残基,而在鸟类进化历史中,某些AMPs的特定密码子位点的多样化也涉及到间歇性正选择。这些发现极大地增进了我们对鸟类AMPs分子进化的理解,将有助于理解它们在鸟类先天免疫反应中的作用。此外,β-防御素和cathelicidin肽的大数据集未来也可能为新型抗菌剂的转化研究和开发提供有价值的资源。