Darling Aaron E, Miklós István, Ragan Mark A
ARC Center of Excellence in Bioinformatics, The University of Queensland, St. Lucia, Queensland, Australia.
PLoS Genet. 2008 Jul 18;4(7):e1000128. doi: 10.1371/journal.pgen.1000128.
Genome structure variation has profound impacts on phenotype in organisms ranging from microbes to humans, yet little is known about how natural selection acts on genome arrangement. Pathogenic bacteria such as Yersinia pestis, which causes bubonic and pneumonic plague, often exhibit a high degree of genomic rearrangement. The recent availability of several Yersinia genomes offers an unprecedented opportunity to study the evolution of genome structure and arrangement. We introduce a set of statistical methods to study patterns of rearrangement in circular chromosomes and apply them to the Yersinia. We constructed a multiple alignment of eight Yersinia genomes using Mauve software to identify 78 conserved segments that are internally free from genome rearrangement. Based on the alignment, we applied Bayesian statistical methods to infer the phylogenetic inversion history of Yersinia. The sampling of genome arrangement reconstructions contains seven parsimonious tree topologies, each having different histories of 79 inversions. Topologies with a greater number of inversions also exist, but were sampled less frequently. The inversion phylogenies agree with results suggested by SNP patterns. We then analyzed reconstructed inversion histories to identify patterns of rearrangement. We confirm an over-representation of "symmetric inversions"-inversions with endpoints that are equally distant from the origin of chromosomal replication. Ancestral genome arrangements demonstrate moderate preference for replichore balance in Yersinia. We found that all inversions are shorter than expected under a neutral model, whereas inversions acting within a single replichore are much shorter than expected. We also found evidence for a canonical configuration of the origin and terminus of replication. Finally, breakpoint reuse analysis reveals that inversions with endpoints proximal to the origin of DNA replication are nearly three times more frequent. Our findings represent the first characterization of genome arrangement evolution in a bacterial population evolving outside laboratory conditions. Insight into the process of genomic rearrangement may further the understanding of pathogen population dynamics and selection on the architecture of circular bacterial chromosomes.
基因组结构变异对从微生物到人类等各种生物体的表型有着深远影响，但对于自然选择如何作用于基因组排列却知之甚少。诸如引起腺鼠疫和肺鼠疫的鼠疫耶尔森菌等致病细菌，常常表现出高度的基因组重排。最近多个耶尔森菌基因组的可得性为研究基因组结构和排列的进化提供了前所未有的机会。我们引入了一组统计方法来研究环状染色体中的重排模式，并将其应用于耶尔森菌。我们使用Mauve软件构建了八个耶尔森菌基因组的多重比对，以识别78个内部无基因组重排的保守片段。基于该比对，我们应用贝叶斯统计方法来推断耶尔森菌的系统发育倒位历史。基因组排列重建的抽样包含七种简约树拓扑结构，每种结构具有不同的79次倒位历史。具有更多倒位的拓扑结构也存在，但抽样频率较低。倒位系统发育与单核苷酸多态性模式所暗示的结果一致。然后我们分析重建的倒位历史以识别重排模式。我们证实了“对称倒位”的过度存在——其端点与染色体复制起点等距的倒位。祖先基因组排列显示出耶尔森菌对复制子平衡有适度偏好。我们发现所有倒位都比中性模型预期的要短，而在单个复制子内起作用的倒位比预期的要短得多。我们还发现了复制起点和终点的典型配置的证据。最后，断点重用分析表明，端点靠近DNA复制起点倒位的频率几乎是其他倒位的三倍。我们的研究结果首次描述了在实验室条件之外进化的细菌群体中的基因组排列进化。对基因组重排过程的深入了解可能会加深对病原体群体动态以及环状细菌染色体结构选择的理解。
