Synonymous Codon Variant Analysis for Autophagic Genes Dysregulated in Neurodegeneration

Neurodegenerative disorders are often a culmination of the accumulation of abnormally folded proteins and defective organelles. Autophagy is a process of removing these defective proteins, organelles, and harmful substances from the body, and it works to maintain homeostasis. If autophagic removal of defective proteins has interfered, it affects neuronal health. Some of the autophagic genes are specifically found to be associated with neurodegenerative phenotypes. Non-functional, mutated, or gene copies having silent mutations, often termed synonymous variants, might explain this. However, these synonymous variant which codes for exactly similar proteins have different translation rates, stability, and gene expression profiling. Hence, it would be interesting to study the pattern of synonymous variant usage. In the study, synonymous variant usage in various transcripts of autophagic genes ATG5, ATG7, ATG8A, ATG16, and ATG17/FIP200 reported to cause neurodegeneration (if dysregulated) is studied. These genes were analyzed for their synonymous variant usage; nucleotide composition; any possible nucleotide skew in a gene; physical properties of autophagic protein including GRAVY and AROMA; hydropathicity; instability index; and frequency of acidic, basic, neutral amino acids; and gene expression level. The study will help understand various evolutionary forces acting on these genes and the possible augmentation of a gene if showing unusual behavior.