Macdonald Stuart J, Long Anthony D
Department of Ecology and Evolutionary Biology, University of California, Irvine, USA.
Mol Biol Evol. 2005 Mar;22(3):607-19. doi: 10.1093/molbev/msi046. Epub 2004 Nov 10.
The Enhancer of split gene complex (E(spl)-C) is one of the more highly annotated gene regions in Drosophila, and the 12 genes within the complex help determine the spacing and patterning of adult bristles. Any E(spl)-C coding, transcribed, or cis-regulatory regions experiencing nonneutral evolution are strong candidates to harbor polymorphisms contributing to naturally occurring variation in bristle number. We confirm that the E(spl)-C is strongly conserved and show that 74% of regulatory elements previously identified in D. melanogaster are conserved in D. pseudoobscura. Regulatory elements in enhancer regions show lower nucleotide diversity and more rare polymorphisms compared with adjacent nonregulatory DNA, suggesting they are under purifying selection, and these effects are particularly pronounced when considering only conserved regulatory elements. The ratio of polymorphism to divergence was significantly different between binding sites and nonbinding sites for transcription factors within enhancer regions, suggesting the action of some form of selection. Too few polymorphisms in regions of the 3' UTR harboring regulatory motifs prevents adequate comparison of diversity and the polymorphism frequency spectrum between 3' UTR motif and nonmotif sequence. We identified at least two broad regions of the gene complex showing strong population subdivision among four populations, which is suggestive of local adaptation or background selection. Finally, two regions of the E(spl)-C exhibit low nucleotide diversity, a high level of rare polymorphisms, and an increase in linkage disequilibrium, which together suggest the action of positive selection. Notably, the gene m2 shows a significant deviation from neutrality by the McDonald-Kreitman test and resides in one of the two regions putatively experiencing a selective sweep. All sites in regions apparently visible to various selective forces are candidates for future work to determine their phenotypic effects.
分裂增强子基因复合体（E(spl)-C）是果蝇中注释程度较高的基因区域之一，该复合体内的12个基因有助于确定成虫刚毛的间距和模式。任何经历非中性进化的E(spl)-C编码、转录或顺式调控区域，都很可能含有导致刚毛数量自然变异的多态性。我们证实E(spl)-C具有高度保守性，并表明先前在黑腹果蝇中鉴定出的调控元件有74%在拟暗果蝇中是保守的。与相邻的非调控DNA相比，增强子区域的调控元件显示出较低的核苷酸多样性和更罕见的多态性，这表明它们受到纯化选择，当仅考虑保守调控元件时，这些效应尤为明显。增强子区域内转录因子结合位点与非结合位点之间的多态性与分化率存在显著差异，这表明存在某种形式的选择作用。3'UTR含有调控基序的区域多态性太少，无法充分比较3'UTR基序与非基序序列之间的多样性和多态性频谱。我们在基因复合体中确定了至少两个广泛区域，在四个种群之间表现出强烈的种群分化，这暗示了局部适应或背景选择。最后，E(spl)-C的两个区域表现出低核苷酸多样性、高水平的罕见多态性以及连锁不平衡增加，这些共同表明存在正选择作用。值得注意的是，基因m2通过麦克唐纳-克雷特曼检验显示出与中性的显著偏差，并且位于两个可能经历选择性清除的区域之一。显然受到各种选择力影响的区域中的所有位点，都是未来确定其表型效应工作的候选对象。
