The high turnover of ribosome-associated transcripts fromde novoORFs produces gene-like characteristics available forde novogene emergence in wild yeast populations

Abstract

Little is known about the rate of emergence of genes de novo, how they spread in populations and what their initial properties are. We examined wild Saccharomyces paradoxus populations to characterize the diversity and turnover of intergenic ORFs over short evolutionary time-scales. We identified ~34,000 intergenic ORFs per individual genome for a total of ~64,000 orthogroups, which resulted from an estimated turnover rate relatively smaller than the rate of gene duplication in yeast. Hundreds of intergenic ORFs show translation signatures, similar to canonical genes, but lower translation efficiency, which could reduce their potential production cost or simply reflect a lack of optimization. Translated intergenic ORFs tend to display low expression levels with sequence properties that are on average closer to expectations based on intergenic sequences.However, some predicted de novo polypeptides with gene-like properties emerged from ancient as well as recent birth events, illustrating that the raw material for functional innovations may appear even over short evolutionary time-scales. Our results suggest that variation in the mutation rate along the genome impacts the turnover of random polypeptides, which may in turn influence their early evolutionary trajectory. Whereas low mutation rate regions allow more time for random intergenic ORFs to evolve and become functional before being lost, mutation hotspots allow for the rapid exploration of the molecular landscape, thereby increasing the probability to acquire a polypeptide with immediate gene-like properties and thus functional potential.

De novo gene birth

“…For many of these, ancestral ORFs were identified but were not expressed. Highlighting the differences between inter- and intra-species comparisons, a study in natural Saccharomyces paradoxus populations found that the number of de novo polypeptides identified more than doubled when considering intra-species diversity [73]. In primates, one early study identified 270 orphan genes (unique to humans, chimpanzees, and macaques), of which 15 were thought to have originated de novo [44], while a later report identified 60 de novo genes in humans alone that are supported by transcriptional and proteomic evidence [66].…”

“…It is notable that even after application of this stringent pipeline, the 152 validated de novo genes that remained still represents a significant fraction of the mouse genome likely to have originated de novo . Generally speaking, however, it remains debated whether duplication and divergence or de novo gene birth represent the dominant mechanism for the emergence of new genes [63, 65, 73, 75–77], in part due to the fact that de novo genes are likely both to emerge and to be lost more frequently than other young genes (see below).…”

“…In wild S . paradoxus populations, de novo ORFs emerge and are lost at similar rates [73]. Similarly, an analysis of five mammalian transcriptomes found that most ORFs in mice were either very old or species specific, implying frequent birth and death of de novo transcripts [77].…”

“…Most non-genic ORFs that are translated appear to be evolving neutrally [73, 75, 116]. The proto-gene model predicts, however, that expression of non-genic ORFs will occasionally provide an adaptive advantage to the cell.…”

“…In wild S . paradoxus populations, ORFs with exaggerated gene-like features are found among the pool of translated intergenic polypeptides [73]. It is not clear whether such ORFs are preferentially retained.…”