Hancock J M, Shaw P J, Bonneton F, Dover G A
MRC Clinical Sciences Centre, Hammersmith Hospital, London, England.
Mol Biol Evol. 1999 Feb;16(2):253-65. doi: 10.1093/oxfordjournals.molbev.a026107.
Extensive sequence analysis of the developmental gene hunchback and its 5' and 3' regulatory regions in Drosophila melanogaster, Drosophila virilis, Musca domestica, and Tribolium castaneum, using a variety of computer algorithms, reveals regions of high sequence simplicity probably generated by slippage-like mechanisms of turnover. No regions are entirely refractory to the action of slippage, although the density and composition of simple sequence motifs varies from region to region. Interestingly, the 5' and 3' flanking regions share short repetitive motifs despite their separation by the gene itself, and the motifs are different in composition from those in the exons and introns. Furthermore, there are high levels of conservation of motifs in equivalent orthologous regions. Detailed sequence analysis of the P2 promoter and DNA footprinting assays reveal that the number, orientation, sequence, spacing, and protein-binding affinities of the BICOID-binding sites varies between species and that the 'P2' promoter, the nanos response element in the 3' untranslated region, and several conserved boxes of sequence in the gene (e.g., the two zinc-finger regions) are surrounded by cryptically-simple-sequence DNA. We argue that high sequence turnover and genetic redundancy permit both the general maintenance of promoter functions through the establishment of coevolutionary (compensatory) changes in cis- and trans-acting genetic elements and, at the same time, the possibility of subtle changes in the regulation of hunchback in the different species.
利用多种计算机算法，对黑腹果蝇、粗壮果蝇、家蝇和赤拟谷盗中发育基因驼背蛋白及其5'和3'调控区域进行了广泛的序列分析，结果显示高度简单的序列区域可能是由类似滑移的周转机制产生的。尽管简单序列基序的密度和组成因区域而异，但没有哪个区域对滑移作用完全具有抗性。有趣的是，5'和3'侧翼区域尽管被基因本身隔开，但仍共享短的重复基序，并且这些基序的组成与外显子和内含子中的不同。此外，在等效的直系同源区域中，基序具有高度的保守性。对P2启动子的详细序列分析和DNA足迹分析表明，双尾结合位点的数量、方向、序列、间距和蛋白质结合亲和力在不同物种之间存在差异，并且“P2”启动子、3'非翻译区中的纳米应答元件以及基因中的几个保守序列框（例如，两个锌指区域）都被隐蔽的简单序列DNA所包围。我们认为，高序列周转和遗传冗余既允许通过建立顺式和反式作用遗传元件的共同进化（补偿）变化来总体维持启动子功能，同时也允许不同物种中驼背蛋白调控发生细微变化的可能性。
