Orphans and new gene origination, a structural and evolutionary perspective

The frequency of de novo creation of proteins has been debated. Early it was assumed that de novo creation should be extremely rare and that the vast majority of all protein coding genes were created in early history of life. However, the early genomics era lead to the insight that protein coding genes do appear to be lineage-specific. Today, with thousands of completely sequenced genomes, this impression remains. It has even been proposed that the creation of novel genes, a continuous process where most de novo genes are short-lived, is as frequent as gene duplications. There exist reports with strongly indicative evidence for de novo gene emergence in many organisms ranging from Bacteria, sometimes generated through bacteriophages, to humans, where orphans appear to be overexpressed in brain and testis. In contrast, research on protein evolution indicates that many very distantly related proteins appear to share partial homology. Here, we discuss recent results on de novo gene emergence, as well as important technical challenges limiting our ability to get a definite answer to the extent of de novo protein creation.