Antimicrobial peptides from hylid and ranin frogs originated from a 150-million-year-old ancestral precursor with a conserved signal peptide but a hypermutable antimicrobial domain
Antimicrobial peptides from hylid and ranin frogs originated from a 150-million-year-old ancestral precursor with a conserved signal peptide but a hypermutable antimicrobial domain
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DOI：
10.1046/j.1432-1033.2003.03584.x
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发表时间：
2003-05-01
期刊：
影响因子：
--
通讯作者：
Amiche, M
中科院分区：
文献类型：
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作者：
Vanhoye, D;Bruston, F;Amiche, M
青蛙的皮肤腺产生抗菌肽，保护皮肤免受有害微生物的侵害，并有助于伤口修复。这些肽的序列是非常不同的，无论是在物种内和物种之间，使5000活的无尾两栖类青蛙可能会产生约100 000种不同的抗菌肽。南美雨蛙的抗菌肽来源于前体preprodermaseptins，其信号肽和插入序列非常保守，但其C-末端结构域差异显著，导致成熟肽具有不同的长度、序列和抗菌谱。我们已经使用了极端保守的preproregion的preprodermaseptin成绩单，以确定这个家庭的新成员在澳大利亚和南美的hylids。所有这些肽都是阳离子的、两亲的和α-螺旋的。它们杀死了广泛的微生物，并发挥协同作用。42 preprodermaseptin基因序列从10种hylid和蛙蛙进行了分析的背景下，他们的胚胎发育和地理学和地球物理模型的冈瓦纳大陆的碎片，以检查这些青蛙已经进化到产生一个巨大的肽抗生素阵列的策略。现代抗微生物肽的超分化和每个物种的肽数量是由大约1.5亿年前的祖先基因的重复复制和成熟肽结构域的加速突变引起的，可能涉及诱变性，易错性，DNA聚合酶类似于大肠杆菌Pol V。具有这种不同结构和作用谱的抗菌肽的存在代表了成功的进化通过为青蛙提供最大限度的保护，防止感染性微生物，并最大限度地减少微生物对单个肽产生耐药性的机会，从而实现多药物防御。超突变的抗菌结构域的有针对性的诱变聚合酶，可以产生许多序列的变化，在几个步骤可能有选择性的生存价值时，青蛙殖民一个新的生态位遇到不同的微生物捕食者。
The dermal glands of frogs produce antimicrobial peptides that protect the skin against noxious microorganisms and assist in wound repair. The sequences of these peptides are very dissimilar, both within and between species, so that the 5000 living anuran frogs may produce approximate to 100 000 different antimicrobial peptides. The antimicrobial peptides of South American hylid frogs are derived from precursors, the preprodermaseptins, whose signal peptides and intervening sequences are remarkably conserved, but their C-terminal domains are markedly diverse, resulting in mature peptides with different lengths, sequences and antimicrobial spectra. We have used the extreme conservation in the preproregion of preprodermaseptin transcripts to identify new members of this family in Australian and South American hylids. All these peptides are cationic, amphipathic and alpha-helical. They killed a broad spectrum of microorganisms and acted in synergy. 42 preprodermaseptin gene sequences from 10 species of hylid and ranin frogs were analyzed in the context of their phylogeny and biogeography and of geophysical models for the fragmentation of Gondwana to examine the strategy that these frogs have evolved to generate an enormous array of peptide antibiotics. The hyperdivergence of modern antimicrobial peptides and the number of peptides per species result from repeated duplications of a approximate to 150-million-year-old ancestral gene and accelerated mutations of the mature peptide domain, probably involving a mutagenic, error-prone, DNA polymerase similar to Escherichia coli Pol V. The presence of antimicrobial peptides with such different structures and spectra of action represents the successful evolution of multidrug defense by providing frogs with maximum protection against infectious microbes and minimizing the chance of microorganisms developing resistance to individual peptides. The hypermutation of the antimicrobial domain by a targeted mutagenic polymerase that can generate many sequence changes in a few steps may have a selective survival value when frogs colonizing a new ecological niche encounter different microbial predators.