Biased distribution of DNA uptake sequences towards genome maintenance genes

Biased distribution of DNA uptake sequences towards genome maintenance genes
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DOI:
10.1093/nar/gkh255
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发表时间:
2004-02-01
影响因子:
14.9
通讯作者:
Tonjum, T
Tonjum, T
中科院分区:
生物学2区
文献类型:
--
作者:
Davidsen, T;Rodland, EA;Tonjum, T

文献摘要

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重复序列特征是所有基因组 DNA 的特征。我们对人类病原体脑膜炎奈瑟菌、淋病奈瑟菌和流感嗜血杆菌中的重复基因组序列进行了严格的搜索,发现编码区内最常见的 9-10 聚体是自然遗传转化所需的 DNA 摄取序列 (DUS)。更重要的是,我们发现参与 DNA 修复、重组、限制性修饰和复制的基因中 DUS 的密度明显高于这些生物体中任何其他注释的基因组。多杀性巴斯德氏菌还表现出与先前在流感嗜血杆菌中鉴定的相同的推定 DUS 的高频率,并且具有向基因组维持基因的倾斜分布,表明该细菌在某些条件下可能具有转化能力。这些结果表明,基因组维护基因中 DUS 的高频率在系统发育不同的物种中是保守的,因此具有重要的生物学意义。 DUS 密度的增加预计会增强 DNA 的摄取,并且 DUS 在基因组维护基因中的过度表达可能反映了基因组保存功能的促进恢复。例如,在发病过程中,只需通过抗突变基因的丢失,就可以允许基因组不稳定性短暂且有益的增加,因为这些包含 DUS 的序列将优先恢复。此外,这些基因的摄取可以提供一种促进基因毒性应激后 DNA 损伤恢复的机制。
Repeated sequence signatures are characteristic features of all genomic DNA. We have made a rigorous search for repeat genomic sequences in the human pathogens Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae and found that by far the most frequent 9-10mers residing within coding regions are the DNA uptake sequences (DUS) required for natural genetic transformation. More importantly, we found a significantly higher density of DUS within genes involved in DNA repair, recombination, restriction-modification and replication than in any other annotated gene group in these organisms. Pasteurella multocida also displayed high frequencies of a putative DUS identical to that previously identified in H. influenzae and with a skewed distribution towards genome maintenance genes, indicating that this bacterium might be transformation competent under certain conditions. These results imply that the high frequency of DUS in genome maintenance genes is conserved among phylogenetically divergent species and thus are of significant biological importance. Increased DUS density is expected to enhance DNA uptake and the over-representation of DUS in genome maintenance genes might reflect facilitated recovery of genome preserving functions. For example, transient and beneficial increase in genome instability can be allowed during pathogenesis simply through loss of antimutator genes, since these DUS-containing sequences will be preferentially recovered. Furthermore, uptake of such genes could provide a mechanism for facilitated recovery from DNA damage after genotoxic stress.