Frequent gain and loss of intronic splicing regulatory elements during the evolution of vertebrates.
Frequent gain and loss of intronic splicing regulatory elements during the evolution of vertebrates.
复制标题
脊椎动物进化过程中内含子剪接调控元件的频繁获得和丢失。
DOI：
10.1093/gbe/evs051
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发表时间：
2012
影响因子：
3.3
通讯作者：
Berglund,JAndrew
中科院分区：
文献类型：
--
作者：
Voelker,RodgerB;Erkelenz,Steffen;Reynoso,Vinicio;Schaal,Heiner;Berglund,JAndrew
剪接调节元件 (SRE) 是由影响附近剪接位点剪接的蛋白质结合的序列。组成型剪接内含子已进化为利用许多不同的剪接因子。影响哪些剪接因子用于个体内含子剪接的进化过程通常尚不清楚。我们证明，在产生哺乳动物的谱系中，许多内含子丢失了富含 U 的序列并获得了富含 G 的序列，这两者都类似于已知的 SRE。富含 U 的 SRE 明显转变为富含 G 的 SRE，表明相关剪接因子在功能上是等效的。为了支持这一点，我们证明富含 U 和富含 G 的 SRE 都能够促进 SRE 依赖性剪接报告基因的剪接。此外，我们证明，使用异源MS2束缚系统（细菌MS2外壳融合蛋白及其RNA茎环结合位点），富含U的SRE结合蛋白（TIA1）和富含G的SRE结合蛋白（HNRNPF）都可以促进同一内含子的剪接。我们还观察到，富含 G 的 SRE 的获得与富含 G/C 的基因组等容线显着相关，这表明 SRE 的获得或损失是由最终导致哺乳动物基因组等容线形成的相同过程驱动的。我们提出了以下哺乳动物 SRE 的增益和损失模型。祖先富含 U 的 SRE 位于经历高 A/T 到 G/C 转化率的基因组区域，会频繁遭受有害突变。然而，同样的过程导致功能等效的富含G的SRE的形成增加，并且获得新的富含G的SRE减少了对富含U的SRE的纯化选择，然后富含U的SRE可以自由腐烂。
Splicing regulatory elements (SREs) are sequences bound by proteins that influence splicing of nearby splice sites. Constitutively spliced introns have evolved to utilize many different splicing factors. The evolutionary processes that influenced which splicing factors are used for splicing of individual introns are generally unclear. We demonstrate that in the lineage that gave rise to mammals, many introns lost U-rich sequences and gained G-rich sequences, both of which resemble known SREs. The apparent conversion of U-rich to G-rich SREs suggests that the associated splicing factors are functionally equivalent. In support of this we demonstrated that U-rich and G-rich SREs are both capable of promoting splicing of an SRE-dependent splicing reporter. Furthermore, we demonstrate, using the heterologous MS2 tethering system (bacterial MS2 coat fusion-protein and its RNA stem-loop binding site), that both the U-rich SRE-binding protein (TIA1) and the G-rich SRE-binding protein (HNRNPF) can promote splicing of the same intron. We also observed that gain of G-rich SREs is significantly associated with G/C-rich genomic isochores, suggesting that gain or loss of SREs was driven by the same processes that ultimately resulted in the formation of mammalian genomic isochores. We propose the following model for the gain and loss of mammalian SREs. Ancestral U-rich SREs located in genomic regions that were experiencing high rates of A/T to G/C conversion would have suffered frequent deleterious mutations. However, this same process resulted in increased formation of functionally equivalent G-rich SREs, and acquisition of new G-rich SREs decreased purifying selection on the U-rich SREs, which were then free to decay.