An evolutionary link between natural transformation and CRISPR adaptive immunity.
An evolutionary link between natural transformation and CRISPR adaptive immunity.
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作者：
Jorth P;Whiteley M
通过感受态细菌的自然转化是水平基因转移的主要手段;然而，感受态驱动细菌多样性和进化的证据仍然难以捉摸。为了验证这一理论，我们使用了一种回顾性的比较基因组学方法来分析Aggregatibacter actinomycetemcomitans的进化历史，Aggregatibacter actinomycetemcomitans是一种具有竞争力和非竞争力姐妹菌株的细菌物种。通过比较基因组分析，我们发现，能力是进化上的基因组多样性和物种形成。在进化过程中经常发生能力丧失，随后是成簇的规则间隔短回文重复序列（CRISPR）的丧失，这是细菌适应性免疫系统，可以保护免受寄生DNA的侵害。相对于非感受态菌株，感受态细菌具有包含多个重排的较大基因组。相反，非感受态细菌基因组非常稳定，但矛盾的是易受感染性DNA元件的影响，这有助于非感受态菌株的遗传多样性。此外，不完全非感受态菌株CRISPR免疫系统富含自靶向元件，这表明CRISPR已被用于细菌基因调控，类似于来自抗病毒RNA干扰途径的真核microRNA。 人体微生物组富含数千种不同的细菌物种。驱动这种多样性的一种机制是通过自然转化进行的水平基因转移，即天然胜任的细菌吸收环境DNA并将新基因纳入其基因组。理论上，能力可以加速进化;然而，试图验证这一理论已经证明是困难的。通过对人类牙周病原体Aggregatibacter actinomycetemcomitans的遗传分析，我们发现了促进基因获取的感受态系统与CRISPR（成簇的规则间隔短回文重复序列）之间的进化联系，CRISPR是保护细菌免受遗传寄生虫侵害的适应性免疫系统。我们发现，有能力的伴放线菌菌株具有许多冗余的CRISPR免疫系统，而无能力的细菌由于失活突变而失去了CRISPR免疫系统。总之，将感受态和CRISPR的进化联系起来的进化数据揭示了促进遗传异质性和新细菌物种兴起的独特机制，为深入了解人体内细菌多样性的复杂机制提供了线索。
Natural transformation by competent bacteria is a primary means of horizontal gene transfer; however, evidence that competence drives bacterial diversity and evolution has remained elusive. To test this theory, we used a retrospective comparative genomic approach to analyze the evolutionary history of Aggregatibacter actinomycetemcomitans, a bacterial species with both competent and noncompetent sister strains. Through comparative genomic analyses, we reveal that competence is evolutionarily linked to genomic diversity and speciation. Competence loss occurs frequently during evolution and is followed by the loss of clustered regularly interspaced short palindromic repeats (CRISPRs), bacterial adaptive immune systems that protect against parasitic DNA. Relative to noncompetent strains, competent bacteria have larger genomes containing multiple rearrangements. In contrast, noncompetent bacterial genomes are extremely stable but paradoxically susceptible to infective DNA elements, which contribute to noncompetent strain genetic diversity. Moreover, incomplete noncompetent strain CRISPR immune systems are enriched for self-targeting elements, which suggests that the CRISPRs have been co-opted for bacterial gene regulation, similar to eukaryotic microRNAs derived from the antiviral RNA interference pathway. The human microbiome is rich with thousands of diverse bacterial species. One mechanism driving this diversity is horizontal gene transfer by natural transformation, whereby naturally competent bacteria take up environmental DNA and incorporate new genes into their genomes. Competence is theorized to accelerate evolution; however, attempts to test this theory have proved difficult. Through genetic analyses of the human periodontal pathogen Aggregatibacter actinomycetemcomitans, we have discovered an evolutionary connection between competence systems promoting gene acquisition and CRISPRs (clustered regularly interspaced short palindromic repeats), adaptive immune systems that protect bacteria against genetic parasites. We show that competent A. actinomycetemcomitans strains have numerous redundant CRISPR immune systems, while noncompetent bacteria have lost their CRISPR immune systems because of inactivating mutations. Together, the evolutionary data linking the evolution of competence and CRISPRs reveals unique mechanisms promoting genetic heterogeneity and the rise of new bacterial species, providing insight into complex mechanisms underlying bacterial diversity in the human body.