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分析 12 种哺乳动物中 HPRT1 基因同义密码子使用模式。

Analysis of synonymous codon usage patterns of HPRT1 gene across twelve mammalian species.

机构信息

College of Agriculture, South China Agricultural University, Guangzhou, China.

Department of Biotechnology, Assam University, Silchar, Assam, India.

出版信息

Genomics. 2020 Jan;112(1):304-311. doi: 10.1016/j.ygeno.2019.02.010. Epub 2019 Feb 25.

Abstract

Genetic changes in Hypoxanthine guanine phosphoribosyltransferace (HPRT1) gene can alter the expression of the dopamine neurotransmitter leads to abnormal neuron function, a disease called Lesch-Nyhan syndrome (LNS). Although different studies were conducted on LNS, information on codon usage bias (CUB) of HPRT1 gene is limited. The present study examines the genetic determinants of CUB in HPRT1 gene using twelve mammalian species. In the coding sequence of HPRT1 genes, A/T ending codons was most frequently used. A higher ENC value was observed indicating lower HPRT1 gene expression in the selected mammalian species. Correlation analysis indicates that compositional constraints under mutation pressure can involve in CUB of HPRT1 genes among the selected mammalian species. Relative synonymous codon usage (RSCU) value revealed that the codons such as ACT, AGG, ATT and AGC were over-represented in each of the mammalian species. Result from the analysis of the RSCU indicates that compositional constraint is a key driver for the variation in codon usage. Ratio of nonsynonymous (dN) and synonymous (dS) substitution further suggested that purifying selection occurs among the HPRT1 gene of studied mammals to maintain its protein function under the process of evolution. Our findings report an insight into the codon usage patterns of HPRT1 gene and will be useful for LNS management.

摘要

遗传改变次黄嘌呤鸟嘌呤磷酸核糖转移酶(HPRT1)基因可以改变多巴胺神经递质的表达,导致异常神经元功能,这种疾病称为 Lesch-Nyhan 综合征(LNS)。尽管对 LNS 进行了不同的研究,但关于 HPRT1 基因密码子使用偏性(CUB)的信息有限。本研究使用 12 种哺乳动物来研究 HPRT1 基因的遗传决定因素。在 HPRT1 基因的编码序列中,A/T 结尾的密码子使用最频繁。观察到更高的 ENC 值表明所选哺乳动物物种中 HPRT1 基因的表达水平较低。相关性分析表明,在所选哺乳动物物种中,突变压力下的组成约束可能涉及 HPRT1 基因的 CUB。相对同义密码子使用(RSCU)值表明,在每种哺乳动物中,密码子如 ACT、AGG、ATT 和 AGC 都过表达。RSCU 分析的结果表明,组成约束是导致密码子使用变异的关键因素。非同义(dN)和同义(dS)取代的比例进一步表明,在进化过程中,研究哺乳动物的 HPRT1 基因发生了纯化选择,以维持其蛋白质功能。我们的研究结果报告了对 HPRT1 基因密码子使用模式的深入了解,这将有助于 LNS 的管理。

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