RT Journal Article SR Electronic T1 Ease of de novo gene birth through spontaneous mutations predicted in a parsimonious model JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.08.23.457309 DO 10.1101/2021.08.23.457309 A1 Somya Mani A1 Tsvi Tlusty YR 2021 UL http://biorxiv.org/content/early/2021/08/24/2021.08.23.457309.abstract AB Contrary to long-held views, recent evidence indicates that de novo birth of genes is not only possible, but is surprisingly prevalent: a substantial fraction of eukaryotic genomes are composed of orphan genes, which show no homology with any conserved genes. And a remarkably large proportion of orphan genes likely originated de novo from non-genic regions. Here, using a parsimonious mathematical model, we investigate the probability and timescale of de novo gene birth due to spontaneous mutations. We trace how an initially non-genic locus accumulates beneficial mutations to become a gene. We sample across a wide range of biologically feasible distributions of fitness effects (DFE) of mutations, and calculate the conditions conducive to gene birth. We find that in a time frame of millions of years, gene birth is highly likely for a wide range of DFEs. Moreover, when we allow DFEs to fluctuate, which is expected given the long time frame, gene birth in the model becomes practically inevitable. This supports the idea that gene birth is a ubiquitous process, and should occur in a wide variety of organisms. Our results also demonstrate that intergenic regions are not inactive and silent but are more like dynamic storehouses of potential genes.Competing Interest StatementThe authors have declared no competing interest.