The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons

To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences. Funding: We thank the Broad Institute Genomics Platform for constructing and sequencing gar DNA and RNA libraries and J. Turner-Maier for the gar transcriptome assembly. We thank the teams of the Bayousphere Research Laboratory (Nicholls State University) and the University of Oregon Fish Facility for gar work and husbandry. We thank J. Westlund for the design of the species illustrations. The generation of gar sequences and assemblies by the Broad Institute of MIT and Harvard University was supported by US National Institutes of Health (NIH)/National Human Genome Research Institute grant U54 HG03067. This work was further supported by US NIH grants R01 OD011116 (alias R01 RR020833) and R24 OD01119004 (J.H.P.); a Feodor Lynen Fellowship from the Alexander von Humboldt Foundation and the Volkswagen Foundation Initiative Evolutionary Biology, grant I/84 815 (I.B.); US NIH grant T32 HD055164 and National Science Foundation (NSF) Doctoral Dissertation Improvement Grant 1311436 (A.R.G.); Uehara Memorial Foundation Research Fellowship 2013, Japan Society for the Promotion of Science Postdoctoral Research Fellowship 2012-127 and Marine Biological Laboratory Research Award 2014 (T.N.); Brazilian National Council for Scientific and Technological Development (CNPq) grants 402754/2012-3 and 477658/2012-1 (I.S