K-ras proto-oncogene (KRAS): Evolutionary dissection on the indispensable predictive and prognostic cancer biomarker across 32 primates

Q4 Biochemistry, Genetics and Molecular Biology Animal Gene Pub Date : 2023-09-01 DOI:10.1016/j.angen.2023.200158

Leonard Whye Kit Lim

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Abstract

The Kirsten rat sarcoma (KRAS) gene is one of the most critical proto-oncogene to target in combating various cancers as its mutation is one of the major cancer-causing causes in most cancers. In this study, we investigated all 32 primate KRAS nucleotide and protein sequences found within the public GenBank database. The Tibetan macaque KRAS protein supersedes the others in terms of amino acid length, molecular weight and isoelectric point. The motif distribution of the Tibetan macaque was also found to vary significantly from the other KRAS proteins examined. Nevertheless, the predicted protein three-dimensional structure of Tibetan macaque did not differ much from that of human and Ugandan red colobus. Fascinatingly, the Coquerel’s sifaka KRAS protein structure and conformation is distinctive from all other 31 primate KRAS proteins. The maximum likelihood phylogenetic tree revealed several potential candidates that are closely related to that of the human KRAS protein to aid future human personalised therapy studies.

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K-ras原癌基因（KRAS）：32种灵长类动物不可或缺的癌症预测和预后生物标志物的进化解剖

Kirsten大鼠肉瘤（KRAS）基因是对抗各种癌症的最关键的原癌基因之一，因为其突变是大多数癌症的主要致癌原因之一。在这项研究中，我们调查了在公共GenBank数据库中发现的所有32个灵长类动物KRAS核苷酸和蛋白质序列。在氨基酸长度、分子量和等电点方面，西藏猕猴KRAS蛋白取代了其他蛋白。西藏猕猴的基序分布也被发现与所检测的其他KRAS蛋白有显著差异。然而，预测的西藏猕猴的蛋白质三维结构与人类和乌干达红疣猴的蛋白质立体结构没有太大差异。令人着迷的是，Coquerel的sifaka KRAS蛋白结构和构象与所有其他31种灵长类KRAS蛋白不同。最大似然系统发育树揭示了几个与人类KRAS蛋白密切相关的潜在候选者，以帮助未来的人类个性化治疗研究。

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Animal Gene Agricultural and Biological Sciences-Insect Science

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期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.