Emergence of novel cephalopod gene regulation and expression through large-scale genome reorganization

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Schmidbaur, H., Kawaguchi, A., Clarence, T., Fu, X., Hoang, O. P., Zimmermann, B., Ritschard, E. A., Weissenbacher, A., Foster, J. S., Nyholm, S., Bates, P. A., Albertin, C. B., Tanaka, E., & Simakov, O. Emergence of novel cephalopod gene regulation and expression through large-scale genome reorganization. Nature Communications, 13(1), (2022): 2172, https://doi.org/10.1038/s41467-022-29694-7.Coleoid cephalopods (squid, cuttlefish, octopus) have the largest nervous system among invertebrates that together with many lineage-specific morphological traits enables complex behaviors. The genomic basis underlying these innovations remains unknown. Using comparative and functional genomics in the model squid Euprymna scolopes, we reveal the unique genomic, topological, and regulatory organization of cephalopod genomes. We show that coleoid cephalopod genomes have been extensively restructured compared to other animals, leading to the emergence of hundreds of tightly linked and evolutionary unique gene clusters (microsyntenies). Such novel microsyntenies correspond to topological compartments with a distinct regulatory structure and contribute to complex expression patterns. In particular, we identify a set of microsyntenies associated with cephalopod innovations (MACIs) broadly enriched in cephalopod nervous system expression. We posit that the emergence of MACIs was instrumental to cephalopod nervous system evolution and propose that microsyntenic profiling will be central to understanding cephalopod innovations.H.S., O.P.H., E.R., and O.S. were supported by the Austrian Science Fund (FWF) grant P30686-B29. O.S. was supported by Whitman Center Early Career Fellowship (Frank R. Lillie Quasi-Endowment Fund, L. & A. Colwin Summer Research Fellowship, Bell Research Award in Tissue Engineering). H.S. was supported by the short-term grant abroad (KWA) of the University of Vienna. H.S. and O.S. were supported by the University of Chicago/Vienna Strategic Partnership Programme Mobility Grant. A.K. was supported by the JSPS Postdoctoral Fellowship for Overseas Researchers program from Japan. C.B.A. was supported by the Hibbitt Early Career Fellowship. Eggs and paralarvae of E. scolopes were generated in part by support by the NASA Space Biology 80NSSC18K1465 awarded to J.S.F. S.V.N. was supported by the National Science Foundation IOS-1557914. This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC0001003), the UK Medical Research Council (FC001003), and the Wellcome Trust (FC001003)