Genome Erosion in Infectious Microorganisms

描述(申请人提供)：对全基因组序列的分析得出的最显著的发现之一是，与真核宿主相关的细菌经历了基因组衰退的过程，这既是通过基因的突变失活发生的，也是通过包含大片区域的缺失发生的。基因丢失和基因组大小缩小在病原体和共生体中普遍存在，似乎与基因获取一样对细菌谱系的进化和多样化至关重要。 这项拟议研究的总体目标是通过解决两个普遍问题来研究基因组退化的过程和后果：(1)是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的缩减和重组过程？直到最近，灭活基因在细菌基因组中还被认为是极其罕见的；然而，全基因组序列的阐明揭示了许多致病细菌包含数百个假基因，通过关注密切相关的致病物种和自由生活的物种，拟议的工作将调查假基因是如何产生并持续存在于细菌基因组中的。尽管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。 总而言之，这项研究有可能揭示作用于细菌基因组的新的选择机制。由于这一提议所考察的过程和考虑的问题对于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.