BACKGROUND Polyglutamine regions (polyQ) are one of the most studied and prevalent homorepeats in eukaryotes. They have a particular length-dependent codon usage, which relates to a characteristic CAG-slippage mechanism. Pathologically expanded tracts of polyQ are known to form aggregates and are involved in the development of several human neurodegenerative diseases. The non-pathogenic function of polyQ is to mediate protein-protein interactions via a coiled-coil pairing with an interactor. They are usually located in a helical context. RESULTS Here we study the stability of polyQ regions in evolution, using a set of 60 proteomes from four distinct taxonomic groups (Insecta, Teleostei, Sauria and Mammalia). The polyQ regions can be distinctly grouped in three categories based on their evolutionary stability: stable, unstable by length variation (inserted), and unstable by mutations (mutated). PolyQ regions in these categories can be significantly distinguished by their glutamine codon usage, and we show that the CAG-slippage mechanism is predominant in inserted polyQ of Sauria and Mammalia. The polyQ amino acid context is also influenced by the polyQ stability, with a higher proportion of proline residues around inserted polyQ. By studying the secondary structure of the sequences surrounding polyQ regions, we found that regarding the structural conformation around a polyQ, its stability category is more relevant than its taxonomic information. The protein-protein interaction capacity of a polyQ is also affected by its stability, as stable polyQ have more interactors than unstable polyQ. CONCLUSIONS Our results show that apart from the sequence of a polyQ, information about its orthologous sequences is needed to assess its function. Codon usage, amino acid context, structural conformation and the protein-protein interaction capacity of polyQ from all studied taxa critically depend on the region stability. There are however some taxa-specific polyQ features that override this importance. We conclude that a taxa-driven evolutionary analysis is of the highest importance for the comprehensive study of any feature of polyglutamine regions.

中文翻译：

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聚谷氨酰胺区域的特征取决于它们的进化稳定性。

背景技术聚谷氨酰胺区域（polyQ）是真核生物中研究最广泛的同质重复序列之一。它们具有与长度有关的特定密码子用法，这与特征性的CAG滑移机制有关。已知polyQ的病理性扩展片段形成聚集体，并参与了几种人类神经退行性疾病的发展。polyQ的非致病性功能是通过与相互作用因子配对的螺旋螺旋介导蛋白质-蛋白质相互作用。它们通常位于螺旋上下文中。结果在这里，我们使用来自四个不同分类组（Insecta，Teleostei，Sauria和Mammalia）的60个蛋白质组，研究了polyQ区在进化中的稳定性。根据polyQ区域的进化稳定性，可以将其分为三类：稳定，因长度变化（插入）而不稳定，而因突变（突变）而不稳定。这些类别中的PolyQ区域可以通过其谷氨酰胺密码子使用来明显区分，并且我们证明了在Sauria和Mammalia插入的polyQ中CAG滑移机制是主要的。polyQ氨基酸环境也受polyQ稳定性的影响，插入的polyQ周围的脯氨酸残基比例更高。通过研究围绕polyQ区域的序列的二级结构，我们发现，关于polyQ周围的结构构象，其稳定性类别比其分类信息更为重要。polyQ的蛋白质-蛋白质相互作用能力也受其稳定性的影响，因为稳定的polyQ比不稳定的polyQ具有更多的相互作用体。结论我们的结果表明，除了polyQ的序列外，需要有关其直系同源序列的信息来评估其功能。来自所有研究的类群的polyQ的密码子使用，氨基酸背景，结构构象和蛋白质-蛋白质相互作用能力主要取决于区域稳定性。但是，有一些特定于分类单元的polyQ功能可以覆盖此重要性。我们得出的结论是，分类学驱动的进化分析对于全面研究聚谷氨酰胺区域的任何特征至关重要。