Evolutionary dynamics and phylogenetic inference of CRISPR systems in prokaryotic populations

原核生物群体中CRISPR系统的进化动力学和系统发育推断

• 批准号: 405974812
• 负责人: Dr. Franz Baumdicker
• 金额: --
• 依托单位: Fachbereich IV: Informatik
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/405974812?language=en
• 关键词: Evolutionary; dynamics; phylogenetic; inference; CRISPR

The revolutionary CRISPR/Cas technology to alter genomes has its origin in the natural CRISPR systems in bacteria and archaea.Many of these systems can act as an adaptive defense system targeting specific viral sequences.Beyond this defensive function, CRISPR systems can influence the evolution of bacterial populations without viruses being involved.The overarching goal of this project is to develop and apply new state of the art models for the evolution of CRISPR in prokaryotes. Many studies have focused on the coevolutionary aspects between CRISPR possessing bacteria and the corresponding viruses. In contrast, we will consider the intrinsic evolution of CRISPR Cas systems in bacteria and archaea. In particular, we aim to answer the following questions:a) To identify specific targets the CRISPR system contains an array of spacers that align with the targets. This spacer array provides a unique insight into the evolutionary history since spacers in this array are arranged in chronological order. Can we explain the observed pattern in spacer arrays and identify spacers under selection?Can we reconstruct ancestral spacer insertion times and link them to their ancestral history?b) Accidental self-targeting usually leads to death such that potential self-targets in the bacterial genome are presumably under strong selection.Can we model the selective effect of self-targeting CRISPR systems from the genome sequences of bacteria possessing CRISPR?c) CRISPR systems that target closely related species are capable to block recombination between bacterial strains and can modulate the frequency of genes in the population. Moreover, bacteria can use such systems as an offensive weapon targeting closely related competitors.How does CRISPR influence the frequency of genes in bacteria?Can we understand within population dynamics of CRISPR arrays targeting related species? Are CRISPR systems targeting subpopulations a promising new anti-microbial treatment?We will address these questions with a mixture of mathematical and computational approaches.

改变基因组的革命性CRISPR/CAS技术起源于细菌和考古中的天然CRISPR系统。这些系统中的许多系统都可以作为针对特定病毒序列的适应性防御系统。在这种防御功能之外，CRISPR系统可以在不涉及病毒的情况下影响细菌种群的进化。本项目的总体目标是开发和应用新的最先进的原核生物CRISPR进化模型。许多研究都集中在CRISPR细菌和相应病毒之间的共同进化方面。相反，我们将考虑CRISPR CAS系统在细菌和古菌中的内在进化。特别是，我们的目标是回答以下问题：a)为了识别特定的目标，CRISPR系统包含与目标对准的间隔物阵列。这种间隔物阵列提供了对进化历史的独特洞察，因为该阵列中的间隔物是按时间顺序排列的。我们能否解释间隔区阵列中观察到的模式并识别选择下的间隔区？我们能否重建祖先间隔区插入时间并将它们与其祖先历史联系起来？b)意外的自靶作用通常会导致死亡，因此细菌基因组中的潜在自靶作用可能处于强烈的选择之下。我们能否根据拥有CRISPR的细菌的基因组序列模拟自靶CRISPR系统的选择效果？c)针对密切相关物种的CRISPR系统能够阻止细菌菌株之间的重组，并能够调节种群中基因的频率。此外，细菌可以利用这样的系统作为攻击武器，瞄准密切相关的竞争对手。CRISPR如何影响细菌中的基因频率？我们能否了解CRISPR阵列针对相关物种的种群动态？针对亚群的CRISPR系统是一种有前途的新的抗微生物治疗方法吗？我们将用数学和计算方法的混合来解决这些问题。