Alqahtani Taha, Khandia Rekha, Puranik Nidhi, Alqahtani Ali M, Alghazwani Yahia, Alshehri Saad Ali, Chidambaram Kumarappan, Kamal Mohammad Amjad
Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
Department of Biochemistry and Genetics, Barkatullah University, Bhopal, India.
Front Genet. 2022 Aug 9;13:884348. doi: 10.3389/fgene.2022.884348. eCollection 2022.
Dementia is a clinical syndrome characterized by progressive cognitive decline, and the symptoms could be gradual, persistent, and progressive. In the present study, we investigated 47 genes that have been linked to dementia. Compositional, selectional, and mutational forces were seen to be involved. Nucleotide components that influenced A- and GC-affected codon usages bias at all three codon positions. The influence of these two compositional constraints on codon usage bias (CUB) was positive for nucleotide A and negative for GC. Nucleotide A also experienced the highest mutational force, and GC-ending codons were preferred over AT-ending codons. A high bias toward GC-ending codons enhances the gene expression level, evidenced by the positive association between CAI- and GC-ending codons. Unusual behavior of the TTG codon showing an inverse relationship with the GC-ending codon and negative influence of gene expression, behavior contrary to all other GC-ending codons, shows an operative selectional force. Furthermore, parity analysis, higher translational selection value, preference of GC-ending codons over AT-ending codons, and association of gene length with gene expression refer to the dominant role of selection pressure with compositional constraint and mutational force-shaping codon usage.
痴呆是一种以进行性认知衰退为特征的临床综合征，其症状可能是渐进性、持续性和进行性的。在本研究中，我们调查了47个与痴呆相关的基因。发现组成、选择和突变力量都在起作用。在所有三个密码子位置，核苷酸成分都影响了受A和GC影响的密码子使用偏好。这两种组成限制对密码子使用偏好（CUB）的影响，对核苷酸A为正，对GC为负。核苷酸A也经历了最高的突变力量，并且以GC结尾的密码子比以AT结尾的密码子更受青睐。对以GC结尾的密码子的高度偏好提高了基因表达水平，这一点通过密码子适应指数（CAI）与以GC结尾的密码子之间的正相关得以证明。TTG密码子的异常行为与以GC结尾的密码子呈负相关且对基因表达有负面影响，这一行为与所有其他以GC结尾的密码子相反，表明存在一种起作用的选择力量。此外，奇偶分析、较高的翻译选择值、以GC结尾的密码子优于以AT结尾的密码子，以及基因长度与基因表达的关联，都表明选择压力在与组成限制和塑造密码子使用的突变力量共同作用中起主导作用。
