Codon Usage Analysis of Pro-Apoptotic Bim Gene Isoforms

Abstract

Background: Bim is a Bcl-2 homology 3 (BH3)-only proteins, a group of pro-apoptotic proteins involved in physiological and pathological conditions. Both the overexpression and under-expression of Bim protein are associated with the diseased condition, and various isoforms of Bim protein are present with differential apoptotic potential. Objective: The present study attempted to envisage the association of various molecular signatures with the codon choices of Bim isoforms. Methods: Molecular signatures like composition, codon usage, nucleotide skews, the free energy of mRNA transcript, physical properties of proteins, codon adaptation index, relative synonymous codon usage, and dinucleotide odds ratio were determined and analyzed for their associations with codon choices of Bim gene. Results: Skew analysis of the Bim gene indicated the preference of C nucleotide over G, A, and T and preference of G over T and A nucleotides was observed. An increase in C content at the first and third codon position increased gene expression while it decreased at the second codon position. Compositional constraints on nucleotide C at all three codon positions affected gene expression. The analysis revealed an exceptionally high usage of CpC dinucleotide in all the envisaged 31 isoforms of Bim. We correlated it with the requirement of rapid demethylation machinery to fine-tune the Bimgene expression. Also, mutational pressure played a dominant role in shaping codon usage bias in Bim isoforms. Conclusion: An exceptionally high usage of CpC dinucleotide in all the envisaged 31 isoforms of Bim indicates a high order selectional force to fine tune Bim gene expression.

Codon Pattern and Compositional Constraints Determination of Genes Associated with Chronic Periodontitis

“…The equilibrium near zero shows high neutrality or mutation forces, while values near one show high selection forces [ 50 ]. The model depicted that 21.77% of the variation in %GC12 results from GC3 component variation [ 26 ].…”

“…Codon bias is often determined by compositional, mutational, or selectional forces [ 24 ]. Codon bias plays a crucial determinant of gene expression levels mainly via influencing transcription [ 25 ], and reports suggest more substantial bias in the case of highly expressed genes due to selection pressure [ 26 ].…”

Codon Usage is Influenced by Compositional Constraints in Genes Associated with Dementia

“…Other researchers also found a relationship between codon bias and nucleotide composition suggestive of mutational force acting on codon bias ( Deb et al, 2020 ). CpC dinucleotide abundance has been reported with the fine-tuning of gene expression also ( Khandia et al, 2022 ). The positive association of odds ratio of A/T-containing dinucleotides (ApA, ApC, ApT, TpA, and TpT) and the positive association of odds ratio of G/C-containing dinucleotides (CpG, GpC, and GpG) with CUB indicated the presence of selectional forces in shaping codon usage.…”

Socio-Demographic and Economic Factors of the Pharmaceutical Market Development in Russia

“…Thus, the generic may not meet the requirements for bioequivalence or therapeutic equivalence. This is not critical when it comes to everyday "simple" medicines, but when it comes to complex drugs with a small difference between active and toxic concentrations or when it is necessary to maintain a specific level of a substance in the blood in a narrow range for a long time, such deviations are unacceptable and can lead to irreparable consequences [11,25].…”