New Genomic Signals Underlying the Emergence of Human Proto-Genes

Abstract

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′ 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′ 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′ UTRs, and domains have specific properties in proto-genes. We also emphasize that the genomic positions of de novo genes strongly impacts these properties.

Evolutionary New Genes in a Growing Paradigm

“…Further analyses indicate that the biased new gene duplicates, expressed in a particular developmental stage, show greater divergence in expression among orthologues and paralogues. The expression analyses also provided new data to support a pattern previously reported in other organisms: new genes show narrower expression patterns across developmental stages or tissues the younger they are, for example, Drosophila [ 6 , 20 ], Oryza [ 21 ], and primates [ 22 ].…”

“…In addition, Grandchamp et al [ 22 ], in this Genes volume, thoroughly examined four properties in human protogenes, i.e., the genes an in early stage of de novo origination [ 29 ]: intron acquisition, regulatory elements, UTRs, and domain evolution. The extensive data were characterized as showing significant differences between protogenes and old genes, revealing a growth process of gene structures with age.…”

Quantification and modeling of turnover dynamics ofde novotranscripts inDrosophila melanogaster

“…To quantify the genomic relationship between the seven lines of D. melanogaster , a dated phylogenetic tree was generated with the software BEAST (Bouckaert et al, 2014). The tree was based on the alignment of the 11,568 longest proteins per genes in common in the seven lines, retrieved from the seven genomes assembled de novo (Grandchamp et al, 2022a), and the date of divergence from European lines to the outgroup Zambian line was set to 12,843 years, following the results of Laurent et al (2011). The Zambian population was well identified as an outgroup population, as expected from its geographic isolation to the European populations (Fig.…”

“…To quantify the genomic relationship between the seven lines of D. melanogaster , a dated phylogenetic tree was estimated with the software BEAST (Bouckaert et al, 2014). The tree is based on the alignment of the 11,568 longest proteins per genes in common in the seven lines, retrieved from the seven genomes assembled de novo (Grandchamp et al, 2022a). The branch lengths are based on a previously estimated date of divergence from European lines to the ancestral African population, here approximated by the Zambian line, and set to 12,843 years (Laurent et al, 2011).…”

“…For Definition 3, a python script was built to directly assess the overlapping positions and nucleotides of de novo transcripts between lines. To test the accuracy of our Definitions, we used a set of 11,000 proto-genes from Grandchamp et al (2022a), and distributed them into orthogroups by using the software OrthoFinder (Emms and Kelly, 2019), and our script for Definition 1. We found 93% of similarity between the results from OrthoFinder and our script (Orthofinder: 5687 orthogroups, Our script: 6124 orthogroups) ((Supplemental deposit)).…”