Genome Erosion in Infectious Microorganisms

描述（由申请人提供）：从全基因组序列分析中出现的最显著的发现之一是，与真核宿主结合的细菌经历基因组衰变过程，这通过基因的突变失活和通过包含大区域的缺失发生。基因丢失和基因组大小减小在病原体和共生体中普遍存在，并且似乎与基因获得对细菌谱系的进化和多样化一样重要。 拟议研究的全球目标是通过解决两个一般性问题来调查基因组降解的过程和后果：（1）什么力量在细菌基因组中假基因的形成，转录失活和消除中起作用，以及（2）什么因素负责基因组减少和重组的过程？直到最近，失活基因被认为是非常罕见的细菌基因组;然而，完整的基因组序列的阐明已经揭示，许多致病细菌含有数百个假基因，通过关注密切相关的致病和自由生活的物种，拟议的工作将调查假基因如何出现和持续存在于细菌基因组中。虽然这些惰性基因以前被认为对生物体没有影响，但它们的维持很可能是有害的，我们将测试选择是否会使某些序列沉默。为了研究细菌基因组降解的动力学，我们将开发和实施新的生物信息学方法来重建基因组收缩和重组的过程，并研究某些初始事件如何影响宿主相关物种的进化轨迹。 累积起来，这项研究有可能揭示作用于细菌基因组的新的选择机制。由于该提案所研究的过程和考虑的问题对不同的生命形式是共同的，这项工作将对解释具有非常不同的生态、生活方式和基因组组织的生物体的基因组信息产生广泛的影响。

DESCRIPTION (provided by applicant): Among the most remarkable findings that have emerged from the analysis of complete genome sequences is that bacteria that become associated with eukaryotic hosts undergo a process of genome decay, which occurs both through the mutational inactivation of genes and through deletions that encompass large regions. Gene loss and genome size reduction are prevalent among pathogens and symbionts, and appear to be as crucial as gene acquisition to the evolution and diversification of bacterial lineages. The global aim of the proposed research is to investigate the process and consequences of genome degradation by addressing two general questions: (1) What forces act in the formation, transcriptional inactivation and elimination of pseudogenes in bacterial genomes, and (2) What factors are responsible for the process of genome reduction and reorganization? Until recently, inactivated genes were thought to be exceedingly rare in bacterial genomes; however, the elucidation of complete genome sequences has revealed that many pathogenic bacteria contain hundreds of pseudogenes, By focusing on closely related pathogenic and free-living species, the proposed work will investigate how pseudogenes arise and persist in bacterial genomes. Although these inert genes have been previously thought be of no consequence to an organism, their maintenance may well be detrimental, and we will test whether selection acts to silence certain sequences. To investigate the dynamics of bacterial genome degradation, we will develop and implement new bioinformatic methods to reconstruct the process of genome contraction and reorganization, and examine how certain initial events have influenced the evolutionary trajectory of host-associated species. Cumulatively, this research has the potential of revealing new selective mechanisms acting on bacterial genomes. And because the processes examined and questions considered by this proposal are common to diverse life forms, this work will have broad impact on the interpretation of genomic information from organisms having very different ecology, lifestyles and genome organization.