Alternative splicing and alternative initiation/termination transcription sites have the potential to greatly expand the proteome in eukaryotes by producing several transcript isoforms from the same gene. Although these mechanisms are well described at the genomic level, little is known about their contribution to protein evolution and their impact at the protein structure level. Here, we address both issues by reconstructing the evolutionary history of transcripts and by modeling the tertiary structures of the corresponding protein isoforms. We reconstruct phylogenetic forests relating 60 protein-coding transcripts from the c-Jun N-terminal kinase (JNK) family observed in seven species. We identify two alternative splicing events of ancient origin and show that they induce subtle changes in the protein's structural dynamics. We highlight a previously uncharacterized transcript whose predicted structure seems stable in solution. We further demonstrate that orphan transcripts, for which no phylogeny could be reconstructed, display peculiar sequence and structural properties. Our approach is implemented in PhyloSofS (Phylogenies of Splicing Isoforms Structures), a fully automated computational tool freely available at https://github.com/PhyloSofS-Team/PhyloSofS.

中文翻译：

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笔录的进化历史和结构动力学为JNK家族的功能多样性提供了机械方面的见解。

替代剪接和替代起始/终止转录位点具有通过从同一基因产生几种转录同工型而极大地扩展真核生物中蛋白质组的潜力。尽管这些机制已在基因组水平上得到了很好的描述，但对它们对蛋白质进化的贡献及其对蛋白质结构水平的影响知之甚少。在这里，我们通过重建转录本的进化历史并通过对相应蛋白质同工型的三级结构建模来解决这两个问题。我们重建从7个物种中观察到的c-Jun N末端激酶（JNK）家族相关的60种蛋白质编码转录本的系统发育森林。我们确定了古代起源的两个替代剪接事件，并表明它们诱导蛋白质的结构动力学的细微变化。我们突出显示了以前未知的转录本，其预测结构在溶液中似乎稳定。我们进一步证明，没有亲缘关系可以重建的孤儿成绩单显示特殊的序列和结构特性。我们的方法在PhyloSofS（剪接异构形式的系统发育）中实现，PhyloSofS是可从https://github.com/PhyloSofS-Team/PhyloSofS免费获得的全自动计算工具。