RT Journal Article SR Electronic T1 De novo emergence of adaptive membrane proteins from thymine-rich intergenic sequences JF bioRxiv FD Cold Spring Harbor Laboratory SP 621532 DO 10.1101/621532 A1 Nikolaos Vakirlis A1 Omer Acar A1 Brian Hsu A1 Nelson Castilho Coelho A1 S. Branden Van Oss A1 Aaron Wacholder A1 Kate Medetgul-Ernar A1 John Iannotta A1 Aoife McLysaght A1 Carlos J. Camacho A1 Allyson F. O’Donnell A1 Trey Ideker A1 Anne-Ruxandra Carvunis YR 2019 UL http://biorxiv.org/content/early/2019/04/29/621532.abstract AB Recent evidence demonstrates that novel protein-coding genes can arise de novo from intergenic loci. This evolutionary innovation is thought to be facilitated by the pervasive translation of intergenic transcripts, which exposes a reservoir of variable polypeptides to natural selection. Do intergenic translation events yield polypeptides with useful biochemical capacities? The answer to this question remains controversial. Here, we systematically characterized how de novo emerging coding sequences impact fitness. In budding yeast, overexpression of these sequences was enriched in beneficial effects, while their disruption was generally inconsequential. We found that beneficial emerging sequences have a strong tendency to encode putative transmembrane proteins, which appears to stem from a cryptic propensity for transmembrane signals throughout thymine-rich intergenic regions of the genome. These findings suggest that novel genes with useful biochemical capacities, such as transmembrane domains, tend to evolve de novo within intergenic loci that already harbored a blueprint for these capacities.