Department of Computer Science, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
PLoS Comput Biol. 2010 Jul 22;6(7):e1000861. doi: 10.1371/journal.pcbi.1000861.
G-quadruplex DNA is a four-stranded DNA structure formed by non-Watson-Crick base pairing between stacked sets of four guanines. Many possible functions have been proposed for this structure, but its in vivo role in the cell is still largely unresolved. We carried out a genome-wide survey of the evolutionary conservation of regions with the potential to form G-quadruplex DNA structures (G4 DNA motifs) across seven yeast species. We found that G4 DNA motifs were significantly more conserved than expected by chance, and the nucleotide-level conservation patterns suggested that the motif conservation was the result of the formation of G4 DNA structures. We characterized the association of conserved and non-conserved G4 DNA motifs in Saccharomyces cerevisiae with more than 40 known genome features and gene classes. Our comprehensive, integrated evolutionary and functional analysis confirmed the previously observed associations of G4 DNA motifs with promoter regions and the rDNA, and it identified several previously unrecognized associations of G4 DNA motifs with genomic features, such as mitotic and meiotic double-strand break sites (DSBs). Conserved G4 DNA motifs maintained strong associations with promoters and the rDNA, but not with DSBs. We also performed the first analysis of G4 DNA motifs in the mitochondria, and surprisingly found a tenfold higher concentration of the motifs in the AT-rich yeast mitochondrial DNA than in nuclear DNA. The evolutionary conservation of the G4 DNA motif and its association with specific genome features supports the hypothesis that G4 DNA has in vivo functions that are under evolutionary constraint.
G-四链体 DNA 是一种由非 Watson-Crick 碱基配对形成的四链 DNA 结构，由堆叠的四组鸟嘌呤组成。人们已经提出了这种结构的许多可能的功能，但它在细胞内的实际作用在很大程度上仍未得到解决。我们对 7 种酵母物种中具有形成 G-四链体 DNA 结构（G4 DNA 基序）潜力的区域进行了全基因组进化保守性调查。我们发现，G4 DNA 基序的保守性明显高于预期的随机水平，核苷酸水平的保守模式表明，基序的保守性是 G4 DNA 结构形成的结果。我们描述了酿酒酵母中保守和非保守 G4 DNA 基序与 40 多种已知基因组特征和基因类别的关联。我们全面的、综合的进化和功能分析证实了之前观察到的 G4 DNA 基序与启动子区和 rDNA 的关联，并确定了 G4 DNA 基序与基因组特征（如有丝分裂和减数分裂双链断裂位点（DSB））的几个以前未被识别的关联。保守的 G4 DNA 基序与启动子和 rDNA 保持着强烈的关联，但与 DSB 没有关联。我们还首次对线粒体中的 G4 DNA 基序进行了分析，令人惊讶的是，在富含 AT 的酵母线粒体 DNA 中发现了比核 DNA 高 10 倍的基序浓度。G4 DNA 基序的进化保守性及其与特定基因组特征的关联支持了 G4 DNA 具有受进化约束的体内功能的假说。
