Human long intrinsically disordered protein regions are frequent targets of positive selection.
Human long intrinsically disordered protein regions are frequent targets of positive selection.
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DOI：
10.1101/gr.232645.117
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发表时间：
2018-07
期刊：
影响因子：
7
通讯作者：
Gossmann TI
中科院分区：
文献类型：
--
作者：
Afanasyeva A;Bockwoldt M;Cooney CR;Heiland I;Gossmann TI
内在无序区域经常出现在蛋白质中，其特点是缺乏明确的三维结构。虽然这些区域没有显示出更高的结构组织顺序，但它们在功能上是重要的。无序区域正在迅速进化，这主要归因于宽松的净化选择和遗传漂变作用的增加。也有人提出，积极选择可能有助于它们的快速多样化。然而，对于我们自己的物种来说，目前尚不清楚在这些蛋白质区域的进化过程中，正选择是否发挥了作用。在这里，我们通过研究超过6600种具有内在无序区域和有序对应区域的人类蛋白质的进化模式来解决这个问题。我们对来自90多种哺乳动物基因组的数据进行比较的方法使用了无序蛋白质区域的先验知识，我们表明，这增加了检测阳性选择的能力，提高了一个数量级。我们可以证实，人类内在紊乱区域的进化速度更快，不仅在人类内部，而且在整个哺乳动物系统发育中都是如此。然而，它们经历了实质性的进化限制，暗示了它们基本功能的重要性。我们发现令人信服的证据表明，无序蛋白质区域是积极选择的频繁目标，并估计人类无序和有序蛋白质区域之间的适应性替代的相对速率不同四倍。我们的研究结果表明，无序蛋白质区域是遗传创新的重要目标，并且这些区域的正选择的贡献比其他蛋白质部分更为明显。
Intrinsically disordered regions occur frequently in proteins and are characterized by a lack of a well-defined three-dimensional structure. Although these regions do not show a higher order of structural organization, they are known to be functionally important. Disordered regions are rapidly evolving, largely attributed to relaxed purifying selection and an increased role of genetic drift. It has also been suggested that positive selection might contribute to their rapid diversification. However, for our own species, it is currently unknown whether positive selection has played a role during the evolution of these protein regions. Here, we address this question by investigating the evolutionary pattern of more than 6600 human proteins with intrinsically disordered regions and their ordered counterparts. Our comparative approach with data from more than 90 mammalian genomes uses a priori knowledge of disordered protein regions, and we show that this increases the power to detect positive selection by an order of magnitude. We can confirm that human intrinsically disordered regions evolve more rapidly, not only within humans but also across the entire mammalian phylogeny. They have, however, experienced substantial evolutionary constraint, hinting at their fundamental functional importance. We find compelling evidence that disordered protein regions are frequent targets of positive selection and estimate that the relative rate of adaptive substitutions differs fourfold between disordered and ordered protein regions in humans. Our results suggest that disordered protein regions are important targets of genetic innovation and that the contribution of positive selection in these regions is more pronounced than in other protein parts.
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DOI：
10.1126/science.1231097
发表时间：
2013-03-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hubbard BP;Gomes AP;Dai H;Li J;Case AW;Considine T;Riera TV;Lee JE;E SY;Lamming DW;Pentelute BL;Schuman ER;Stevens LA;Ling AJ;Armour SM;Michan S;Zhao H;Jiang Y;Sweitzer SM;Blum CA;Disch JS;Ng PY;Howitz KT;Rolo AP;Hamuro Y;Moss J;Perni RB;Ellis JL;Vlasuk GP;Sinclair DA
通讯作者：
Sinclair DA
影响因子：
4.4
作者：
Chen, JW;Romero, P;Dunker, AK
通讯作者：
Dunker, AK
影响因子：
10.7
作者：
Fletcher W;Yang Z
通讯作者：
Yang Z
影响因子：
4.8
作者：
Bondensgaard, Kent;Breinholt, Jens;Hjorth, Siv A.
通讯作者：
Hjorth, Siv A.
影响因子：
10.7
作者：
Eyre-Walker, Adam;Keightley, Peter D.
通讯作者：
Keightley, Peter D.