Repurposing the Dark Genome – I: Reverse Proteins

Overview & Synopsis

Abstract:In the genome's blueprint, three distinct sequence categories emerge:sequences accountable for protein encoding, RNA encoding, and sequences that play no role in expression. We asked: If evolution favoured sequences for metabolic functions, to what extent is untapped (non-expressing) and underutilized (solely RNA encoding) information accessible for continued innovation? These questions drive us to experimentally create functional proteins through the utilization of intergenic sequences from E. coli, as published by Dhar et al. in 2009. This ongoing study extends the scope of the original report and explores the potential of reading naturally evolved genes in reverse order to unlock novel proteins or peptides. Using the full length reverse gene data in C.elegans, we computationally translated 20,000 C. elegans protein-coding genes in reverse direction to construct a virtual library of 188 ‘full-length and first-in-the-class’ proteins. Here, we present a brief account of these reverse proteins in terms of their sequence similarities, structural details, stability, function and cellular address.This approach opens up new opportunities of designing novel proteins and peptides towards functional outcomes. Currently the experimental studies are going on. In future, we plan to expand the search space to other model organisms and provide a public access of this new data for further experimental validation. Keywords: Reverse coding, synthetic proteins, synthetic biology, genomics.