New Genomic Signals Underlying the Emergence of Human Proto-Genes

De novo genes are novel genes which emerge from non-coding DNA. Until now, little is known about de novo genes' properties, correlated to their age and mechanisms of emergence. In this study, we investigate four related properties: introns, upstream regulatory motifs, 5 & PRIME; Untranslated regions (UTRs) and protein domains, in 23,135 human proto-genes. We found that proto-genes contain introns, whose number and position correlates with the genomic position of proto-gene emergence. The origin of these introns is debated, as our results suggest that 41% of proto-genes might have captured existing introns, and 13.7% of them do not splice the ORF. We show that proto-genes which emerged via overprinting tend to be more enriched in core promotor motifs, while intergenic and intronic genes are more enriched in enhancers, even if the TATA motif is most commonly found upstream in these genes. Intergenic and intronic 5 & PRIME; UTRs of proto-genes have a lower potential to stabilise mRNA structures than exonic proto-genes and established human genes. Finally, we confirm that proteins expressed by proto-genes gain new putative domains with age. Overall, we find that regulatory motifs inducing transcription and translation of previously non-coding sequences may facilitate proto-gene emergence. Our study demonstrates that introns, 5 & PRIME; UTRs, and domains have specific properties in proto-genes. We also emphasize that the genomic positions of de novo genes strongly impacts these properties.

Automated summary

De novo genes are novel genes that emerge from non-coding DNA. This study investigates the properties of these genes, such as intron presence and position, regulatory motifs, untranslated regions (UTRs), and protein domains. The findings suggest that introns may have been captured by a significant portion of de novo genes, and the emergence mechanism impacts the enrichment of certain motifs. Additionally, the stability of mRNA structures and the acquisition of new protein domains with age are observed. Overall, the genomic position of de novo genes strongly influences their properties.