Intrinsically disordered proteins (IDPs) contain regions lacking intrinsic globular structure (intrinsically disordered regions, IDRs). IDPs are present across the tree of life, with great variability of IDR type and frequency even between closely related taxa. To investigate the function of IDRs, we evaluated and compared the distribution of disorder content in 10,695 reference proteomes, confirming its high variability and finding certain correlation along the Euteleostomi (bony vertebrates) lineage to number of cell types. We used the comparison of orthologs to study the function of disorder related to increase in cell types, observing that multiple interacting subunits of protein complexes might gain IDRs in evolution, thus stressing the function of IDRs in modulating protein-protein interactions, particularly in the cell nucleus. Interestingly, the conservation of local compositional biases of IDPs follows residue-type specific patterns, with E- and K-rich regions being evolutionarily stable and Q- and A-rich regions being more dynamic. We provide a framework for targeted evolutionary studies of the emergence of IDRs. We believe that, given the large variability of IDR distributions in different species, studies using this evolutionary perspective are required.

中文翻译：

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蛋白质序列紊乱的进化研究

内在无序蛋白质 (IDP) 包含缺乏内在球状结构的区域（内在无序区域，IDR）。IDP 存在于整个生命之树中，即使在密切相关的分类群之间，IDR 类型和频率也存在很大差异。为了研究 IDR 的功能，我们评估并比较了 10,695 个参考蛋白质组中紊乱内容的分布，确认了其高度可变性并发现了沿 Euteleostomi（骨脊椎动物）谱系与细胞类型数量的某些相关性。我们使用直系同源物的比较来研究与细胞类型增加相关的疾病的功能，观察到蛋白质复合物的多个相互作用亚基可能在进化中获得 IDR，从而强调 IDR 在调节蛋白质 - 蛋白质相互作用中的功能，特别是在细胞中核。有趣的是，IDP 局部组成偏差的保守遵循残基类型的特定模式，富含 E 和 K 的区域进化稳定，富含 Q 和 A 的区域更具活力。我们为 IDR 出现的有针对性的进化研究提供了一个框架。我们认为，鉴于不同物种的 IDR 分布差异很大，需要使用这种进化观点进行研究。