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In-silico Codon Context and Synonymous Usage Analysis of Genes for Molecular Mechanisms Inducing Autophagy and
Rekha Khandia1, Pankaj Gurjar2,3, Victoria Romashchenko4
1Department of Biochemistry and Genetics, Barkatullah University, Bhopal, India.
Background:
Autophagy and apoptosis are cellular processes that maintain cellular homeostasis and remove damaged or aged organelles or aggregated and misfolded proteins. Stress factors initiate the signaling pathways common to autophagy and apoptosis. An imbalance in the autophagy and apoptosis, led by cascade of molecular mechanism prior to both processes culminate into neurodegeneration.
Objective:
In present study, we urge to investigate the codon usage pattern of genes which are common before initiating autophagy and apoptosis.
Methods:
In the present study, we took up eleven genes (DAPK1, BECN1, PIK3C3 (VPS34), BCL2, MAPK8, BNIP3 L (NIX), PMAIP1, BAD, BID, BBC3, MCL1) that are part of molecular signaling mechanism prior to autophagy and apoptosis. We analyzed dinucleotide odds ratio, codon bias, usage, context, and rare codon analysis.
Results:
CpC and GpG dinucleotides were abundant, with the dominance of G/C ending codons as preferred codons. Clustering analysis revealed that MAPK8 had a distinct codon usage pattern compared to other envisaged genes. Both positive and negative contexts were observed, and GAG-GAG followed by CTG-GCC was the most abundant codon pair. Of the six synonymous arginine codons, two codons CGT and CGA were the rarest.
Conclusions:
The information presented in the study may be used to manipulate the process of autophagy and apoptosis and to check the pathophysiology associated with their dysregulation.
Insights
This study analyzes codon usage in genes linked to autophagy and apoptosis, revealing distinct patterns in MAPK8 and identifying rare arginine codons. This information could help manipulate these cellular processes and understand neurodegeneration.
Area of Science:
- Molecular Biology
- Genetics
- Cellular Biology
Background:
- Autophagy and apoptosis are crucial cellular processes for maintaining homeostasis and removing damaged components.
- Dysregulation of these processes, triggered by stress, can lead to neurodegeneration.
- Shared molecular mechanisms precede both autophagy and apoptosis, making their study critical.
Purpose of the Study:
- To investigate the codon usage patterns of genes involved in the molecular signaling pathways preceding autophagy and apoptosis.
- To identify specific codon preferences and biases within these key genes.
Main Methods:
- Analysis of eleven genes (DAPK1, BECN1, PIK3C3, BCL2, MAPK8, BNIP3L, PMAIP1, BAD, BID, BBC3, MCL1) common to autophagy and apoptosis signaling.
- Evaluation of dinucleotide odds ratio, codon bias, usage, context, and rare codon frequency.
Main Results:
- Abundant CpC and GpG dinucleotides were observed, with a preference for G/C-ending codons.
- Clustering analysis highlighted a unique codon usage pattern in the MAPK8 gene.
- The codon pair GAG-GAG was most frequent, and CGT and CGA were identified as the rarest arginine codons.
Conclusions:
- The findings provide insights into the codon usage patterns of genes regulating autophagy and apoptosis.
- Understanding these patterns may enable manipulation of autophagy and apoptosis.
- This research can contribute to understanding the pathophysiology of neurodegenerative diseases linked to these cellular processes.
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