In-silico Codon Context and Synonymous Usage Analysis of Genes for Molecular Mechanisms Inducing Autophagy and Apoptosis with Reference to Neurodegenerative Disorders

Article type: Research Article

Authors: Khandia, Rekha^{a; *} | Gurjar, Pankaj^{b; c; *} | Romashchenko, Victoria^d | Al-Hussain, Sami A.^e | Alexiou, Athanasios^{c; f; g; h} | Zouganelis, George^{i; *} | Zaki, Magdi E.A.^{e; *}

Affiliations: [a] Department of Biochemistry and Genetics, Barkatullah University, Bhopal, India | [b] Centre for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India | [c] Department of Science and Engineering, Novel Global Community Educational Foundation, NSW, Australia | [d] RERC Pharmacy, RUDN University, Moscow, Russian Federation | [e] Department of Chemistry, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia | [f] University Centre for Research & Development, Chandigarh University, Chandigarh-Ludhiana Highway, Mohali, Punjab, India | [g] Department of Research & Development, Funogen, Athens, Greece | [h] Department of Research & Development, AFNP Med, Wienna, Austria | [i] School of Human Sciences, College of Life and Natural Sciences, University of Derby, Kedleston Road, Derby, UK

Correspondence: [*] Correspondence to: Rekha Khandia, Department of Biochemistry and Genetics, Barkatullah University, Bhopal 462026 MP, India. E-mails: rekha.khandia@bubhopal.ac.in, bu.rekha.khandia@gmail.com; Pankaj Gurjar, Centre for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu; India. E-mail: pankajgurjar0103@gmail.com; George Zouganelis, School of Human Sciences, College of Life and Natural Sciences, University of Derby, Kedleston Road, Derby, DE22 1GBm, UK. E-mail: g.zouganelis@derby.ac.uk; and Magdi E.A. Zaki, Department of Chemistry, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia. E-mail: mezaki@imamu.edu.sa.

Abstract: 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.

Keywords: Alzheimer’s disease, apoptosis, autophagy, codon context, codon pairs, rare codons, relative synonymous codon usage

DOI: 10.3233/JAD-240158

Journal: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 927-939, 2024