Metfies Katja, Medlin Linda K
Alfred Wegener Institute for Polar and Marine Research, Am Handelshafen 12, D-27570 Bremerhaven, Germany.
Appl Environ Microbiol. 2008 May;74(9):2814-21. doi: 10.1128/AEM.02122-07. Epub 2008 Mar 7.
DNA microarray technology offers the possibility to analyze microbial communities without cultivation, thus benefiting biodiversity studies. We developed a DNA phylochip to assess phytoplankton diversity and transferred 18S rRNA probes from dot blot or fluorescent in situ hybridization (FISH) analyses to a microarray format. Similar studies with 16S rRNA probes have been done determined that in order to achieve a signal on the microarray, the 16S rRNA molecule had to be fragmented, or PCR amplicons had to be <150 bp in length to minimize the formation of a secondary structure in the molecule so that the probe could bind to the target site. We found different results with the 18S rRNA molecule. Four out of 12 FISH probes exhibited false-negative signals on the microarray; eight exhibited strong but variable signals using full-length 18S RNA molecules. A systematic investigation of the probe's accessibility to the 18S rRNA gene was made using Prymenisum parvum as the target. Fourteen additional probes identical to this target covered the regions not tested with existing FISH probes. Probes with a binding site in the first 900 bp of the gene generated positive signals. Six out of nine probes binding in the last 900 bp of the gene produced no signal. Our results suggest that although secondary structure affected probe binding, the effect is not the same for the 18S rRNA gene and the 16S rRNA gene. For the 16S rRNA gene, the secondary structure is stronger in the first half of the molecule, whereas in the 18S rRNA gene, the last half of the molecule is critical. Probe-binding sites within 18S rRNA gene molecules are important for the probe design for DNA phylochips because signal intensity appears to be correlated with the secondary structure at the binding site in this molecule. If probes are designed from the first half of the 18S rRNA molecule, then full-length 18S rRNA molecules can be used in the hybridization on the chip, avoiding the fragmentation and the necessity for the short PCR amplicons that are associated with using the 16S rRNA molecule. Thus, the 18S rRNA molecule is a more attractive molecule for use in environmental studies where some level of quantification is desired. Target size was a minor problem, whereas for 16S rRNA molecules target size rather than probe site was important.
DNA微阵列技术为分析未培养的微生物群落提供了可能,从而有利于生物多样性研究。我们开发了一种DNA系统发育芯片来评估浮游植物的多样性,并将来自斑点印迹或荧光原位杂交(FISH)分析的18S rRNA探针转移到微阵列格式中。对16S rRNA探针进行的类似研究已确定,为了在微阵列上获得信号,16S rRNA分子必须被片段化,或者PCR扩增子的长度必须小于150 bp,以尽量减少分子中二级结构的形成,以便探针能够与靶位点结合。我们对18S rRNA分子得到了不同的结果。12个FISH探针中有4个在微阵列上显示假阴性信号;8个使用全长18S RNA分子显示出强但可变的信号。以微小原甲藻为靶标,对探针与18S rRNA基因的可及性进行了系统研究。另外14个与该靶标相同的探针覆盖了现有FISH探针未检测的区域。在基因前900 bp中有结合位点的探针产生阳性信号。在基因后900 bp中结合的9个探针中有6个没有产生信号。我们的结果表明,虽然二级结构影响探针结合,但对18S rRNA基因和16S rRNA基因的影响并不相同。对于16S rRNA基因,分子前半部分的二级结构更强,而对于18S rRNA基因,分子后半部分至关重要。18S rRNA基因分子内的探针结合位点对于DNA系统发育芯片的探针设计很重要,因为信号强度似乎与该分子结合位点的二级结构相关。如果从18S rRNA分子的前半部分设计探针,那么全长18S rRNA分子可用于芯片杂交,避免了与使用16S rRNA分子相关的片段化和短PCR扩增子的必要性。因此,在需要一定程度定量的环境研究中,18S rRNA分子是更具吸引力的分子。靶标大小是一个小问题,而对于16S rRNA分子,靶标大小而非探针位点很重要。