Jabbir Farwa, Irfan Muhammad, Mustafa Ghulam, Ahmad Hafiz Ishfaq
Department of Biotechnology, University of Sargodha, Pakistan.
Department of Biotechnology, University of Sargodha, Sargodha 40100, Pakistan.
Crit Rev Eukaryot Gene Expr. 2019;29(6):551-564. doi: 10.1615/CritRevEukaryotGeneExpr.2019030785.
BRCA1 and BRCA2 are the two major vulnerability genes involved in hereditary breast cancer. BRCA1 gene programs for a tumor suppressor protein that helps in repairing DNA. The purpose of this study was to reveal the position and nature of amino acid residues involved in breast cancer, and it provides a complete characterization of BRCA1 and its evolutionary relationship with 34 selected organisms. The sequences were retrieved from NCBI, and after analyzing them in BLAST, a complete annotation of both types of genes from a human was done; in addition, a phylogenetic analysis was performed from 34 different organisms to study evolutionary relationships of BRCA1. A total of 1080 positions of genes were found in the dataset in which the first 3 were noncoding positions and the remaining were all coding regions. A tree was originated using MEGA that showed strong evolutionary relationships among three orders (Catertiodactyla, carnivore, and primates) of these organisms, which are closely related to each other. All features of wild and mutant proteins were studied by ProtParam. The location and number of alpha helices, beta sheets, coils, strands, and the binding regions, disordered regions were identified using different tools (SOPMA, PHD, and GOR4) and their percentages greatly varied. Our study revealed that the BRCA1 gene involved in cancer development had a weaker selection than those involved in sporadic cancer. Our investigation showed that in mammals, selection acting on human cancer genes drives adaptive variations in behaviors related to organismal fitness, rather than select for biological roles directly linked to cancer.
BRCA1和BRCA2是遗传性乳腺癌中涉及的两个主要易感基因。BRCA1基因编码一种有助于修复DNA的肿瘤抑制蛋白。本研究的目的是揭示参与乳腺癌的氨基酸残基的位置和性质，并对BRCA1及其与34种选定生物体的进化关系进行全面表征。序列从NCBI检索，在BLAST中对其进行分析后，对人类的这两种基因进行了完整注释；此外，对34种不同生物体进行了系统发育分析，以研究BRCA1的进化关系。数据集中共发现1080个基因位置，其中前3个是非编码位置，其余均为编码区域。使用MEGA生成的一棵树显示了这些生物体的三个目（偶蹄目、食肉目和灵长目）之间有很强的进化关系，它们彼此密切相关。通过ProtParam研究了野生型和突变型蛋白质的所有特征。使用不同工具（SOPMA、PHD和GOR4）鉴定了α螺旋、β折叠、卷曲、链以及结合区域、无序区域的位置和数量，它们的百分比差异很大。我们的研究表明，参与癌症发展的BRCA1基因的选择压力比散发性癌症中的要弱。我们的调查显示，在哺乳动物中，作用于人类癌症基因的选择驱动了与生物体适应性相关行为的适应性变异，而不是直接选择与癌症直接相关的生物学作用。
