Intergenic polyA/T tracts explain the propensity of yeast de novo genes to encode transmembrane domains.

New genes can emerge de novo from non-genic genomic regions. In budding yeast, computational predictions have shown that intergenic regions harbor a higher-than-expected propensity to encode transmembrane domains, if theoretically translated into proteins. This propensity seems to be linked to the high prevalence of predicted transmembrane domains in evolutionarily young genes. However, what accounts for this enriched propensity is not known. Here we show that specific arrangements of polyA/T tracts, which are abundant and enriched in yeast intergenic regions, explain this observation. These tracts are known to function as Nucleosome Depleted Regions, which prevent or reduce nucleosome formation to enable transcription of surrounding genes. We provide evidence that these polyA/T tracts have been repeatedly coopted through de novo gene emergence for the evolution of novel small genes encoding proteins with predicted transmembrane domains. These findings support a previously proposed "transmembrane-first" model of de novo gene birth and help explain why evolutionarily young yeast genes are rich in transmembrane domains. They contribute to our understanding of the process of de novo gene evolution and show how seemingly distinct but potentially interacting levels of functionality can exist within the same genomic loci.