Entire genome transcription across evolutionary time exposes non-coding DNA to de novo gene emergence

Abstract

Even in the best studied Mammalian genomes, less than 5% of the total genome length is annotated as exonic. However, deep sequencing analysis in humans has shown that around 40% of the genome may be covered by poly-adenylated non-coding transcripts occurring at low levels1. Their functional significance is unclear2,3, and there has been a dispute whether they should be considered as noise of the transcriptional machinery4,5. We propose that if such transcripts show some evolutionary stability they will serve as substrates for de novo gene evolution, i.e. gene emergence out of non-coding DNA6-8. Here, we characterize the phylogenetic turnover of low-level poly-adenylated transcripts in a comprehensive sampling of populations, sub-species and species of the genus Mus, spanning a phylogenetic distance of about 10 Myr. We find evidence for more evolutionary stable gains of transcription than losses among closely related taxa, balanced by a loss of older transcripts across the whole phylogeny. We show that adding taxa increases the genomic transcript coverage and that no major transcript-free islands exist over time. This suggests that the entire genome can be transcribed into polyadenylated RNA when viewed at an evolutionary time scale. Thus, any part of the \"non-coding\" genome can become subject to evolutionary functionalization via de novo gene evolution.