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Application of codon usage and context analysis in genes up- or down-regulated in neurodegeneration and cancer to
Rekha Khandia1, Megha Katare Pandey2, Magdi E A Zaki3
1Department of Biochemistry and Genetics, Barkatullah University, Bhopal, Madhya Pradesh, India.
Introduction:
Neurodegeneration and cancer present in comorbidities with inverse effects due to the expression of genes and pathways acting in opposition. Identifying and studying the genes simultaneously up or downregulated during morbidities helps curb both ailments together.
Methods:
This study examines four genes. Three of these (Amyloid Beta Precursor Protein (APP), Cyclin D1 (CCND1), and Cyclin E2 (CCNE2) are upregulated, and one protein phosphatase 2 phosphatase activator (PTPA) is simultaneously downregulated in both disorders. We investigated molecular patterns, codon usage, codon usage bias, nucleotide bias in the third codon position, preferred codons, preferred codon pairs, rare codons, and codon context.
Results:
Parity analysis revealed that T is preferred over A, and G is preferred over C in the third codon position, suggesting composition plays no role in nucleotide bias in both the upregulated and downregulated gene sets and that mutational forces are stronger in upregulated gene sets than in downregulated ones. Transcript length influenced the overall %A composition and codon bias, and the codon AGG exerted the strongest influence on codon usage in both the upregulated and downregulated gene sets. Codons ending in G/C were preferred for 16 amino acids, and glutamic acid-, aspartic acid-, leucine-, valine-, and phenylalanine-initiated codon pairs were preferred in all genes. Codons CTA (Leu), GTA (Val), CAA (Gln), and CGT (Arg) were underrepresented in all examined genes.
Discussion:
Using advanced gene editing tools such as CRISPR/Cas or any other gene augmentation technique, these recoded genes may be introduced into the human body to optimize gene expression levels to augment neurodegeneration and cancer therapeutic regimens simultaneously.
Insights
This study identifies genes simultaneously up or downregulated in neurodegeneration and cancer. Analyzing codon usage bias in genes like APP, CCND1, CCNE2, and PTPA offers new therapeutic targets for both diseases.
Area of Science:
- Genetics and Molecular Biology
- Neuroscience
- Oncology
Background:
- Neurodegenerative diseases and cancer often occur together as comorbidities.
- Opposing gene expression patterns contribute to the inverse relationship between these conditions.
- Identifying shared molecular targets is crucial for simultaneous therapeutic intervention.
Purpose of the Study:
- To investigate molecular patterns, codon usage, and nucleotide bias in genes implicated in both neurodegeneration and cancer.
- To identify specific genes that are either upregulated or downregulated in both disease states.
- To explore the potential of these genes as therapeutic targets for combined treatment strategies.
Main Methods:
- Analysis of four key genes: Amyloid Beta Precursor Protein (APP), Cyclin D1 (CCND1), Cyclin E2 (CCNE2) (upregulated), and Protein Phosphatase 2 Phosphatase Activator (PTPA) (downregulated).
- Investigation of codon usage, codon usage bias, nucleotide bias at the third codon position, preferred codons, preferred codon pairs, rare codons, and codon context.
- Parity analysis to assess nucleotide preferences and mutational forces.
Main Results:
- Nucleotide T is preferred over A, and G over C in the third codon position, indicating stronger mutational forces in upregulated gene sets.
- Transcript length significantly influences overall nucleotide composition and codon bias.
- The codon AGG showed the strongest influence on codon usage; specific codons (CTA, GTA, CAA, CGT) were underrepresented across all examined genes.
Conclusions:
- Codon usage patterns reveal distinct biases in genes associated with neurodegeneration and cancer.
- Specific codon preferences and underrepresentations offer insights into gene regulation in these comorbidities.
- Targeted gene recoding strategies, potentially using CRISPR/Cas, could optimize gene expression for simultaneous treatment of neurodegeneration and cancer.
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