Evolution of the avian β-defensin and cathelicidin genes.
Evolution of the avian β-defensin and cathelicidin genes.
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DOI：
10.1186/s12862-015-0465-3
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发表时间：
2015-09-15
影响因子：
3.4
通讯作者：
Burt DW
中科院分区：
文献类型：
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作者：
Cheng Y;Prickett MD;Gutowska W;Kuo R;Belov K;Burt DW
β-防御素和cathelicidins是两个具有广泛抗菌活性的阳离子抗菌肽（AMP）家族，是先天免疫系统的关键组分。由于它们在宿主防御快速进化的病原体中的重要作用，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。本研究对来自32目53种鸟类的β-防御素和cathelicidins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-防御素基因簇由13个亚家族组成。其中9个在所有鸟类中保守为一对一的直系同源物，而其他的（AvBD 1，AvBD 3，AvBD 7和AvBD 14）在特定的鸟类谱系中更容易发生基因复制或假基因化事件。禽类cathelicidins是一个由三个亚家族组成的基因簇，具有种特异性重复和基因丢失。有证据表明，禽类cathelicidin的原片段和成熟肽结构域可能以这样的方式共同进化，即成熟肽的阳离子性在肽分泌之前被原片段的负电荷部分中和（通过重复对灵长类cathelicidin的分析获得的进一步证据）。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cathelicidins功能至关重要的氨基酸残基，而偶发性正选择也参与驱动鸟类进化历史中某些AMP的特定密码子位点的多样化。这些发现极大地提高了我们对鸟类AMP分子进化的理解，并将有助于了解它们在鸟类先天免疫反应中的作用。此外，β-防御素和cathelicidin肽的大数据集也可能为未来新型抗菌药物的转化研究和开发提供有价值的资源。本文的在线版本（doi：10.1186/s12862-015-0465-3）包含补充材料，可供授权用户使用。
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. The online version of this article (doi:10.1186/s12862-015-0465-3) contains supplementary material, which is available to authorized users.