PT - JOURNAL ARTICLE AU - Gareth B. Gillard AU - Lars Grønvold AU - Line L. Røsæg AU - Matilde Mengkrog Holen AU - Øystein Monsen AU - Ben F. Koop AU - Eric B. Rondeau AU - Manu Kumar Gundappa AU - John Mendoza AU - Daniel J. Macqueen AU - Rori V. Rohlfs AU - Simen R. Sandve AU - Torgeir R. Hvidsten TI - Comparative regulomics reveals pervasive selection on gene dosage following whole genome duplication AID - 10.1101/2020.07.20.212316 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.07.20.212316 4099 - http://biorxiv.org/content/early/2020/08/27/2020.07.20.212316.short 4100 - http://biorxiv.org/content/early/2020/08/27/2020.07.20.212316.full 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 in 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.