Zhao Yiran, Zhang Yu, Feng Jiaxing, He Zixian, Li Ting
College of Life Sciences, Yunlong District, Xuzhou Medical University, No. 209, Tongshan Road, Xuzhou City, Jiangsu, 221000, China.
Mol Neurobiol. 2025 Mar;62(3):3508-3522. doi: 10.1007/s12035-024-04426-8. Epub 2024 Sep 21.
More and more attention has been paid to the role of synonymous substitution in evolution, in which codon usage preference can affect gene expression distribution and protein structure and function. Vesicular glutamate transporter (VGLUT) consists of three isoforms, among which VGLUT3 is significantly different from other VGLUTs in functional importance, expression level, and distribution range, whose reason is still unclear. This study sought to analyze the role of codon preference in VGLUT differentiation. To conduct an evolutionary analysis of the three VGLUTs, this paper uses bioinformatics research methods to analyze the coding sequences of the three VGLUTs in different species and compare the codon usage patterns. Furthermore, the differences among the three VGLUTs were analyzed by combining functional importance, expression level, distribution range, gene structure, protein relationship network, expression at specific developmental stages, and phylogenetic tree, and the influence of codon usage pattern was explored. The results showed that the VGLUT with greater codon preference had less functional importance, lower expression levels, more peripheral distribution away from the CNS, smaller exon density of gene, less conserved and farther away from the CDS region miRNA regulatory sites, simpler and less tight protein interaction networks, delayed developmental expression, and more distant evolutionary relationships. Codon usage preference is a potential factor affecting VGLUT developmental expression and protein evolution.
同义替换在进化中的作用已受到越来越多的关注,其中密码子使用偏好会影响基因表达分布以及蛋白质结构和功能。囊泡谷氨酸转运体(VGLUT)由三种亚型组成,其中VGLUT3在功能重要性、表达水平和分布范围方面与其他VGLUTs有显著差异,其原因尚不清楚。本研究旨在分析密码子偏好在VGLUT分化中的作用。为了对三种VGLUTs进行进化分析,本文采用生物信息学研究方法分析不同物种中三种VGLUTs的编码序列,并比较密码子使用模式。此外,结合功能重要性、表达水平、分布范围、基因结构、蛋白质关系网络、特定发育阶段的表达以及系统发育树,分析了三种VGLUTs之间的差异,并探讨了密码子使用模式的影响。结果表明,密码子偏好性较高的VGLUT功能重要性较低、表达水平较低、在远离中枢神经系统的外周分布较多、基因的外显子密度较小、保守性较低且远离CDS区域的miRNA调控位点、蛋白质相互作用网络更简单且不紧密、发育表达延迟以及进化关系更远。密码子使用偏好是影响VGLUT发育表达和蛋白质进化的一个潜在因素。