Nelakurti Devi D, Rossetti Tiffany, Husbands Aman Y, Petreaca Ruben C
Biomedical Science Undergraduate Program, The Ohio State University Medical School, Columbus, OH 43210, USA.
Biology Undergraduate Program, The Ohio State University, Marion, OH 43302, USA.
Cancers (Basel). 2021 Dec 14;13(24):6274. doi: 10.3390/cancers13246274.
Arginine is encoded by six different codons. Base pair changes in any of these codons can have a broad spectrum of effects including substitutions to twelve different amino acids, eighteen synonymous changes, and two stop codons. Four amino acids (histidine, cysteine, glutamine, and tryptophan) account for over 75% of amino acid substitutions of arginine. This suggests that a mutational bias, or "purifying selection", mechanism is at work. This bias appears to be driven by C > T and G > A transitions in four of the six arginine codons, a signature that is universal and independent of cancer tissue of origin or histology. Here, we provide a review of the available literature and reanalyze publicly available data from the Catalogue of Somatic Mutations in Cancer (COSMIC). Our analysis identifies several genes with an arginine substitution bias. These include known factors such as IDH1, as well as previously unreported genes, including four cancer driver genes (FGFR3, PPP6C, MAX, GNAQ). We propose that base pair substitution bias and amino acid physiology both play a role in purifying selection. This model may explain the documented arginine substitution bias in cancers.
精氨酸由六个不同的密码子编码。这些密码子中任何一个的碱基对变化都可能产生广泛的影响，包括替换为十二种不同的氨基酸、十八种同义变化以及两个终止密码子。四种氨基酸（组氨酸、半胱氨酸、谷氨酰胺和色氨酸）占精氨酸氨基酸替换的75%以上。这表明一种突变偏向或“纯化选择”机制在起作用。这种偏向似乎是由六个精氨酸密码子中的四个发生的C>T和G>A转换驱动的，这是一种普遍存在的特征，与癌症组织的起源或组织学无关。在这里，我们对现有文献进行综述，并重新分析来自癌症体细胞突变目录（COSMIC）的公开可用数据。我们的分析确定了几个存在精氨酸替换偏向的基因。这些基因包括已知的因素如异柠檬酸脱氢酶1（IDH1），以及先前未报道的基因，包括四个癌症驱动基因（成纤维细胞生长因子受体3（FGFR3）、蛋白磷酸酶6C（PPP6C）、原癌基因MAX（MAX）、鸟嘌呤核苷酸结合蛋白Gq亚基α（GNAQ））。我们提出碱基对替换偏向和氨基酸生理学在纯化选择中都起作用。这个模型可能解释了癌症中记录的精氨酸替换偏向。
