RT Journal Article SR Electronic T1 Comparative regulomics reveals pervasive selection on gene dosage following whole genome duplication JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.07.20.212316 DO 10.1101/2020.07.20.212316 A1 Gareth B. Gillard A1 Lars Grønvold A1 Line Røsæg A1 Matilde Mekrog Holen A1 Øystein Monsen A1 Ben F. Koop A1 Eric B. Rondeau A1 Manu Kumar Gundappa A1 John Mendoza A1 Daniel J. Macqueen A1 Rori V. Rohlfs A1 Simen R. Sandve A1 Torgeir R. Hvidsten YR 2020 UL http://biorxiv.org/content/early/2020/07/20/2020.07.20.212316.abstract AB Whole genome duplication (WGD) events have played a major role in eukaryotic genome evolution, but the consequence of these extreme events in adaptive genome evolution is still not well understood. To address this knowledge gap we used a comparative phylogenetic model and transcriptomic data from seven species to infer selection on gene expression in duplicated genes (ohnologs) following the salmonid WGD 80-100 million years ago. We find rare cases of tissue-specific expression evolution but pervasive expression evolution affecting many tissues, reflecting strong selection on maintenance of genome stability following genome doubling. Although ohnolog expression levels have evolved mostly asymmetrically, by diverting one ohnolog copy down a path towards pseudogenization, strong evolutionary constraints have frequently also favoured symmetric shifts in gene dosage of both copies, likely to achieve gene dose reduction while avoiding accumulation of ‘toxic mutations’. Mechanistically, ohnolog regulatory divergence is dictated by the number of bound transcription factors in promoters, with transposable elements being one source of novel binding sites driving tissue-specific gains expression. Our results imply pervasive adaptive expression evolution following WGD to overcome the immediate challenges posed by genome doubling and to exploit the long-term genetic opportunities for novel phenotype evolution.Competing Interest StatementThe authors have declared no competing interest.