Young genes are highly disordered as predicted by the preadaptation hypothesis of de novo gene birth

Abstract

The phenomenon of de novo gene birth from junk DNA is surprising, because random polypeptides are expected to be toxic. There are two conflicting views about how de novo gene birth is nevertheless possible: the continuum hypothesis invokes a gradual gene birth process, while the preadaptation hypothesis predicts that young genes will show extreme levels of gene-like traits. We show that intrinsic structural disorder conforms to the predictions of the preadaptation hypothesis and falsifies the continuum hypothesis, with all genes having higher levels than translated junk DNA, but young genes having the highest level of all. Results are robust to homology detection bias, to the non-independence of multiple members of the same gene family, and to the false positive annotation of protein-coding genes.

Gene Birth Contributes to Structural Disorder Encoded by Overlapping Genes

“…We used IUPred (Dosztányi et al 2005) to calculate ISD values for each sequence. Following Wilson et al (2017), before running IUPred, we excised all cysteines from each amino acid sequence, because of the uncertainty about their disulfide bond status and hence entropy (Uversky and Dunker 2010). Whether cysteine forms a disulfide bond depends on whether it is in an oxidizing or reducing environment.…”

Foldability of a Natural De Novo Evolved Protein

“…Recently born de novo proteins have been predicted by sequence analysis to have high levels of intrinsic disorder on average (Wilson et al, 2017), but no systematic experimental study of their ability to fold has been done. The antifreeze protein AFGP from Antarctic Notothenioid fishes contains a tripeptide repeat that evolved de novo from a splice junction in a trypsinogen gene (Chen et al, 1997), and the unusual structure of the repeat region, matching its unusual function as an antifreeze protein, has been probed by numerous methods (Urbanczyk et al, 2017).…”

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

“…A small fraction of translated ORFs that recently appears have several gene-like characteristics, suggesting that they are pre-adapted to be biochemically functional, while most have some characteristics but not others, meaning that they would require refinement by natural selection to acquire these traits. These observations could reconcile the two opposing models of de novo gene birth (Carvunis et al 2012;Wilson et al 2017). Ongoing de novo genes would be more likely to progressively acquire gene-like properties in slowly evolving regions (low mutation rate) before being lost, as in the continuum model.…”

“…6B-C). The lower intrinsic disorder for iORFsT1 was also observed for random intergenic sequences in Wilson's study (Wilson et al 2017). …”

“…Translated intergenic polypeptides display a high variability for gene-like traits A recent study suggested that selection favors pre-adapted de novo young genes with a high level of protein disorder (ISD) compared to old genes, whereas random polypeptides in intergenic regions are one average less disordered (Wilson et al 2017). This would suggest that young polypeptides with an adaptive potential would already be biased in terms of protein structural properties compared to the neutral expectations based on random sequences.…”