Case studies on potential G-quadruplex-forming sequences from the bacterial orders Deinococcales and Thermales derived from a survey of published genomes.
Case studies on potential G-quadruplex-forming sequences from the bacterial orders Deinococcales and Thermales derived from a survey of published genomes.
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DOI：
10.1038/s41598-018-33944-4
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发表时间：
2018-10-24
影响因子：
4.6
通讯作者：
Burrows CJ
中科院分区：
文献类型：
--
作者：
Ding Y;Fleming AM;Burrows CJ
基因组提供了一个储存化学信息的平台，这些信息在生物体蓬勃发展的环境下必须是稳定的。2 '-脱氧鸟苷（G）核苷酸具有提供超出其沃森-克里克碱基配对能力的额外化学信息的潜力。具有四个或更多个三个G核苷酸的运行的序列各自是可以采用G-四链体折叠的潜在G-四链体形成序列（PQS）。在此，我们分析了来自NCBI数据库的测序基因组以确定基因组序列的PQS密度。首先，我们发现具有大基因组的生物体，包括人类，短吻鳄和玉米，具有相似的PQS密度（约300 PQS/Mbp），并且基因组显著富集具有超过四个G轨道的PQS。微生物基因组分析发现PQS密度的多样性更大。一般来说，PQS密度与基因组的GC%正相关。与这一观察结果相一致的是来自嗜热菌的基因组，它们的PQS比随机预期的要多得多。对这些PQS在Thermales目注释基因组中的位置进行分析表明，这些富含G的序列是随机分布的;相反，在Deinocococcales目中，PQS富集并偏向于基因的转录起始位点。通过生物物理方法研究了四种代表性的PQS，其中两种来自Thermales和Deinocococcales，以建立它们折叠成G-四链体的能力。实验发现，Thermales中的两个PQS不采用G-四链体折叠，而Deinocococcales中最常见的两个PQS采用稳定的平行链G-四链体。这些发现导致了一种假设，即嗜热生物富含PQS是不可避免的结果，以热稳定其基因组在高温下生活;相反，在Deinocococcales中发现的抗应激细菌的基因组可能利用PQS进行基因调控。
Genomes provide a platform for storage of chemical information that must be stable under the context in which an organism thrives. The 2‘-deoxyguanosine (G) nucleotide has the potential to provide additional chemical information beyond its Watson-Crick base-pairing capacity. Sequences with four or more runs of three G nucleotides each are potential G-quadruplex forming sequences (PQSs) that can adopt G-quadruplex folds. Herein, we analyzed sequenced genomes from the NCBI database to determine the PQS densities of the genome sequences. First, we found organisms with large genomes, including humans, alligators, and maize, have similar densities of PQSs (~300 PQSs/Mbp), and the genomes are significantly enriched in PQSs with more than four G tracks. Analysis of microorganism genomes found a greater diversity of PQS densities. In general, PQS densities positively tracked with the GC% of the genome. Exceptions to this observation were the genomes from thermophiles that had many more PQSs than expected by random chance. Analysis of the location of these PQSs in annotated genomes from the order Thermales showed these G-rich sequences to be randomly distributed; in contrast, in the order Deinococcales the PQSs were enriched and biased around transcription start sites of genes. Four representative PQSs, two each from the Thermales and Deinococcales, were studied by biophysical methods to establish the ability of them to fold to G-quadruplexes. The experiments found the two PQSs in the Thermales did not adopt G-quadruplex folds, while the two most common in the Deinococcales adopted stable parallel-stranded G-quadruplexes. The findings lead to a hypothesis that thermophilic organisms are enriched with PQSs as an unavoidable consequence to stabilize thermally their genomes to live at high temperature; in contrast, the genomes from stress-resistant bacteria found in the Deinococcales may utilize PQSs for gene regulatory purposes.
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