TY - JOUR T1 - TRNP1 sequence, function and regulation co-evolve with cortical folding in mammals JF - bioRxiv DO - 10.1101/2021.02.05.429919 SP - 2021.02.05.429919 AU - Zane Kliesmete AU - Lucas E. Wange AU - Beate Vieth AU - Miriam Esgleas AU - Jessica Radmer AU - Matthias Hülsmann AU - Johanna Geuder AU - Daniel Richter AU - Mari Ohnuki AU - Magdalena Götz AU - Ines Hellmann AU - Wolfgang Enard Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/02/06/2021.02.05.429919.abstract N2 - Genomes can be seen as notebooks of evolution that contain unique information on successful genetic experiments1. This allows to identify conserved genomic sequences2 and is very useful e.g. for finding disease-associated variants3. Additional information from genome comparisons across species can be leveraged when considering phenotypic variance across species. Here, we exemplify such a cross-species association study for the gene TRNP1 that is important for mammalian brain development. We find that the rate of TRNP1 protein evolution is highly correlated with the rate of cortical folding across mammals and that TRNP1 proteins from species with more cortical folding induce higher proliferation rates in neural stem cells. Furthermore, we identify a regulatory element in TRNP1 whose activity correlates with cortical folding in Old World Monkeys and Apes. Our analyses indicate that coding and regulatory changes in TRNP1 have modulated its activity to adjust cortical folding during mammalian evolution and provide a blueprint for cross-species association studies.Competing Interest StatementThe authors have declared no competing interest. ER -