Exploring the Peptide Potential of Genomes.

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• The noncoding genome is increasingly recognized as a source of novel genes.
• Widespread transcription and translation of noncoding RNAs yield a vast repertoire of peptides.
• Understanding the structural properties of these peptides is key to de novo protein evolution.

Purpose of the Study:

• To present a computational protocol for exploring a genome's potential to produce novel peptides.
• To characterize the fold potential and structural properties of peptides derived from open reading frames (ORFs).
• To investigate the fold potential of translated ORFs in mouse long noncoding RNAs (lncRNAs).

Main Methods:

• Genome-wide annotation of all open reading frames (ORFs), including coding and noncoding.
• In silico characterization of peptide structural properties, focusing on fold potential.
• Application of the protocol to a small genome, with scalability for large genomes.
• Case study analyzing 721 translated ORFs in mouse lncRNAs using ribosome profiling data.

Main Results:

• The developed protocol can be applied to genomes of varying sizes.
• Translated ORFs in mouse lncRNAs exhibit distinct fold potential distributions compared to non-translated lncRNAs and other noncoding ORFs.
• This suggests a unique structural characteristic of peptides emerging from actively translated noncoding regions.

Conclusions:

• The noncoding genome is a significant source of novel peptide diversity with evolutionary potential.
• The presented protocol provides a framework for identifying and characterizing potentially functional de novo peptides.
• The distinct fold potential of translated lncRNA ORFs highlights their potential role in generating novel protein structures and functions.