RT Journal Article
SR Electronic
T1 TRNP1 sequence, function and regulation co-evolve with cortical folding in mammals
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.05.429919
DO 10.1101/2021.02.05.429919
A1 Zane Kliesmete
A1 Lucas E. Wange
A1 Beate Vieth
A1 Miriam Esgleas
A1 Jessica Radmer
A1 Matthias Hülsmann
A1 Johanna Geuder
A1 Daniel Richter
A1 Mari Ohnuki
A1 Magdalena Götz
A1 Ines Hellmann
A1 Wolfgang Enard
YR 2021
UL http://biorxiv.org/content/early/2021/02/06/2021.02.05.429919.abstract
AB 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.