The (non)malignancy of cancerous amino acidic substitutions
The (non)malignancy of cancerous amino acidic substitutions
复制标题
癌性氨基酸取代的（非）恶性
DOI：
--
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
J. Thornton
中科院分区：
文献类型：
--
作者：
David Talavera;Martin S. Taylor;J. Thornton
自然选择的过程既作用于种群中的个体生物，也作用于生物体内发展成癌症的个体细胞。在这项工作中，我们已经朝着理解在这些不同的情况下施加在人类基因组上的选择压力的差异迈出了第一步。关注单个氨基酸取代，我们发现癌症相关突变（CRM）经常出现在进化保守的位点，而单个氨基酸多态性（SAP）往往出现在进化压力更宽松的位点。那些被归类为癌症驱动突变的CRM显示出比乘客突变更大的保守位点富集。与此相一致，驱动突变富集了注释为关键功能残基及其邻居的位点，并且比偶然预期更可能位于蛋白质表面。总体而言，CRM和多态性的模式非常相似，但我们确实看到了一个明确的信号，表明对癌症驱动突变中破坏性氨基酸取代的多样化选择。这些突变出现的最终结果必须对肿瘤细胞有利，导致细胞群体生长和迁移事件，类似于自然生态系统中所见。Proteins 2010.© 2009 Wiley利斯公司
The process of natural selection acts both on individual organisms within a population and on individual cells within an organism as they develop into cancer. In this work, we have taken a first step toward understanding the differences in selection pressures exerted on the human genome under these disparate circumstances. Focusing on single amino acid substitutions, we have found that cancer‐related mutations (CRMs) are frequent in evolutionarily conserved sites, whereas single amino acid polymorphisms (SAPs) tend to appear in sites having a more relaxed evolutionary pressure. Those CRMs classed as cancer driver mutations show greater enrichment for conserved sites than passenger mutations. Consistent with this, driver mutations are enriched for sites annotated as key functional residues and their neighbors, and are more likely to be located on the surface of proteins than expected by chance. Overall the pattern of CRM and polymorphism is remarkably similar, but we do see a clear signal indicative of diversifying selection for disruptive amino acid substitutions in the cancer driver mutations. The ultimate consequence of the appearance of those mutations must be advantageous for the tumor cell, leading to cell population‐growth and migration events similar to those seen in natural ecosystems. Proteins 2010. © 2009 Wiley‐Liss, Inc.
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影响因子：
4.4
作者：
A. Torkamani;N. Schork
通讯作者：
A. Torkamani;N. Schork
影响因子：
11.2
作者：
Torkamani, Ali;Schork, Nicholas J.
通讯作者：
Schork, Nicholas J.
影响因子：
11.2
作者：
Nikolsky, Yuri;Sviridov, Evgeny;Polyak, Kornelia
通讯作者：
Polyak, Kornelia
影响因子：
9.7
作者：
Torkamani, Ali;Verkhivker, Gennady;Schork, Nicholas J.
通讯作者：
Schork, Nicholas J.
DOI：
10.1073/pnas.180320897
发表时间：
2000-10-24
影响因子：
11.1
作者：
Rodin, SN;Rodin, AS
通讯作者：
Rodin, AS