Repurposing the dark genome. II - Reverse Proteins

Abstract

Based on the expression blueprint encoded in the genome, three groups of sequences have been identified : protein encoding, RNA encoding, and non-expressing. We asked: Why did nature choose a particular DNA sequence for expression? Did she sample every possibility, approving some for RNA synthesis, some for protein synthesis, and retiring/ignoring the rest? If evolution randomly selected sequences for metabolic trials, how much non-utilized (not-expressing) and under-utilized (only RNA encoding) information is currently available for innovations? These questions lead us to experimentally synthesizing functional proteins from intergenic sequences of E.coli (Dhar et al 2009). The current work is an extension of this original report and takes into consideration natural protein-coding sequences read backwards to generate a new possibility. Reverse proteins are full-length translation equivalents of the existing protein-coding genes in the -1 frame. The structural, functional and interaction predictions of reverse proteins in E.coli, S.cerevisiae and D.melanogaster, open up a new opportunity of experimentally producing first-in-the-class proteins towards functional endpoints. This study points to a huge untapped genomic space in organisms from the fundamental biology and applications perspectives.

Repurposing the dark genome. IV – noncoding proteins

“…The work took an interest turn when tRNAencoded peptides were experimentally produced and found to have strong anti-Leishmania property (Chakrabarti et al 2022). More recently, functional protein were predicted from the antisense strand and reverse strands of DNA (Garg et al, 2023, Nayak et al, 2023.…”