Repurposing the dark genome. I - Antisense Proteins

Abstract

From the functional standpoint, the genome may be considered a collection of three types of sequences: protein encoding, RNA encoding, and non-expressing. Based on the standard sequencing and annotation work, it is now well accepted that a small proportion of the genome has been allocated the job of encoding proteins, while most of the genome encodes RNA, and some DNA sequences are not used for expression. The exact ratio among these three types of sequences varies based on the organism. We asked: Is it possible to artificially encode protein and peptide sequences from naturally non-expressing (dark genome) sequences? This led to proof of the concept of making functional proteins from the intergenic sequences of E.coli (Dhar et al 2009). This study is an extension of the original concept and has been organized around antisense DNA sequences. The full-length antisense gene equivalents in forward and reverse orientations were computationally studied for their structural, cellular location, and functional properties, leading to many interesting observations. The current study points to a huge untapped genomic space that needs to be examined from cell physiology, evolutionary, and application perspectives.