Center for Computational Molecular Biology, Brown University, Providence, RI, 02912, USA.
Ecology and Evolutionary Biology, Brown University, Providence, RI, 02912, USA.
Nat Commun. 2020 Jun 5;11(1):2845. doi: 10.1038/s41467-020-16673-z.
Exonic splicing enhancers (ESEs) are enriched in exons relative to introns and bind splicing activators. This study considers a fundamental question of co-evolution: How did ESE motifs become enriched in exons prior to the evolution of ESE recognition? We hypothesize that the high exon to intron motif ratios necessary for ESE function were created by mutational bias coupled with purifying selection on the protein code. These two forces retain certain coding motifs in exons while passively depleting them from introns. Through the use of simulations, genomic analyses, and high throughput splicing assays, we confirm the key predictions of this hypothesis, including an overlap between protein and splicing information in ESEs. We discuss the implications of mutational bias as an evolutionary driver in other cis-regulatory systems.
外显子剪接增强子（ESEs）在exon 中相对于 intron 更为丰富，并与剪接激活因子结合。本研究考虑了一个共同进化的基本问题：在 ESE 识别进化之前，ESE 基序如何在 exons 中富集？我们假设，ESE 功能所需的高 exon 与 intron 基序比是由突变偏向与对蛋白质编码的纯化选择共同创造的。这两种力量保留了某些编码基序在 exons 中，同时将它们从 introns 中被动耗尽。通过使用模拟、基因组分析和高通量剪接分析，我们证实了这一假设的关键预测，包括 ESE 中蛋白质和剪接信息之间的重叠。我们讨论了突变偏向作为其他顺式调控系统进化驱动力的影响。
