Saad Ismail If, Saha Saurav B, Thomas George
Department of Zoology, Faculty of Science, Omar Al Mukhtar University, Al Bayda, Libya.
Department of Computational Biology and Bioinformatics, JSBB, SHIATS, Allahabad - 211007, India.
Bioinformation. 2014 May 20;10(5):293-8. doi: 10.6026/97320630010293. eCollection 2014.
In the development of multicellularity, signaling proteins has played a very important role. Among them, RAS family is one of the most widely studied protein family. However, evolutionary analysis has been carried out mainly on super family level leaving sub family information in scanty. Thus, a subfamily evolutionary study on RAS evolutionary expansion is imperative as it will aid in better drug designing against dreadful diseases like Cancer and other developmental diseases. The present study was aimed to understand RAS evolution on both holistic as well as reductive level. All human RAS family genes and protein were subjected to BLAST tools to find orthologs and paralogs with different parameters followed by phylogenetic tree generation. Our results clearly showed that H-RAS is the most primitive RAS in higher eukaryotes and then diverged into other RAS family members due to different gene modification events. Furthermore, a site specific selection pressure analysis was carried out using SELECTON server which showed that H-RAS, M-RAS and N-RAS are evolving faster than K-RAS and R-RAS. Thus, the results ascertain a new ground to cancer biologists to exploit negatively selected K-RAS and R-RAS as potent drug targets in cancer therapeutics.
在多细胞生物的发育过程中，信号蛋白发挥了非常重要的作用。其中，RAS家族是研究最为广泛的蛋白家族之一。然而，进化分析主要是在超家族水平上进行的，亚家族信息非常匮乏。因此，对RAS进化扩张进行亚家族进化研究势在必行，因为这将有助于更好地设计针对癌症和其他发育性疾病等可怕疾病的药物。本研究旨在从整体和简化水平上了解RAS的进化。对所有人类RAS家族基因和蛋白使用BLAST工具，通过不同参数寻找直系同源物和旁系同源物，随后构建系统发育树。我们的结果清楚地表明，H-RAS是高等真核生物中最原始的RAS，然后由于不同的基因修饰事件分化为其他RAS家族成员。此外，使用SELECTON服务器进行了位点特异性选择压力分析，结果表明H-RAS、M-RAS和N-RAS的进化速度比K-RAS和R-RAS快。因此，这些结果为癌症生物学家在癌症治疗中将负选择的K-RAS和R-RAS作为潜在药物靶点开拓了新的领域。
