Fact or fiction: updates on how protein-coding genes might emerge de novo from previously non-coding DNA

Abstract

Over the last few years, there has been an increasing amount of evidence for the de novo emergence of protein-coding genes, i.e. out of non-coding DNA. Here, we review the current literature and summarize the state of the field. We focus specifically on open questions and challenges in the study of de novo protein-coding genes such as the identification and verification of de novo-emerged genes. The greatest obstacle to date is the lack of high-quality genomic data with very short divergence times which could help precisely pin down the location of origin of a de novo gene. We conclude that, while there is plenty of evidence from a genetics perspective, there is a lack of functional studies of bona fide de novo genes and almost no knowledge about protein structures and how they come about during the emergence of de novo protein-coding genes. We suggest that future studies should concentrate on the functional and structural characterization of de novo protein-coding genes as well as the detailed study of the emergence of functional de novo protein-coding genes.

Keywords: De novo protein evolution; de novo genes; gene emergence; novel genes; protein-coding genes.

Figure 1.. Schematic depiction of de novo protein-coding gene emergence.

Shown is the hypothesis of a step-wise genic and structural maturation of an intergenic sequence towards a protein-coding gene. The steps are each shown as pictograms of protein and gene structure. An exemplary phylogenetic tree is shown to the right. The status of the protein/gene is projected onto the tree using grey, dotted lines. Gene emergence is depicted using a green star, gene loss using a grey X symbol. ORF, open reading frame.