Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv 69978, Israel.
Cell Rep. 2012 May 31;1(5):543-56. doi: 10.1016/j.celrep.2012.03.013. Epub 2012 May 3.
During evolution segments of homeothermic genomes underwent a GC content increase. Our analyses reveal that two exon-intron architectures have evolved from an ancestral state of low GC content exons flanked by short introns with a lower GC content. One group underwent a GC content elevation that abolished the differential exon-intron GC content, with introns remaining short. The other group retained the overall low GC content as well as the differential exon-intron GC content, and is associated with longer introns. We show that differential exon-intron GC content regulates exon inclusion level in this group, in which disease-associated mutations often lead to exon skipping. This group's exons also display higher nucleosome occupancy compared to flanking introns and exons of the other group, thus "marking" them for spliceosomal recognition. Collectively, our results reveal that differential exon-intron GC content is a previously unidentified determinant of exon selection and argue that the two GC content architectures reflect the two mechanisms by which splicing signals are recognized: exon definition and intron definition.
在进化过程中，恒温动物基因组的某些片段经历了 GC 含量的增加。我们的分析表明，两种外显子-内含子结构是从低 GC 含量的外显子和短内含子（GC 含量较低）组成的祖先状态进化而来的。一组经历了 GC 含量的升高，从而消除了外显子-内含子 GC 含量的差异，内含子仍然较短。另一组保留了整体低 GC 含量以及外显子-内含子 GC 含量的差异，并且与较长的内含子相关。我们表明，外显子-内含子 GC 含量差异在外显子包含水平上进行调控，在这种情况下，疾病相关突变通常导致外显子跳过。与另一组的侧翼内含子和外显子相比，该组的外显子还显示出更高的核小体占有率，因此它们被剪接体识别。总的来说，我们的结果表明，外显子-内含子 GC 含量差异是外显子选择的一个以前未被识别的决定因素，并认为这两种 GC 含量结构反映了剪接信号识别的两种机制：外显子定义和内含子定义。
