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An RNA gene expressed during cortical development evolved rapidly in humans

Nature volume 443, pages 167–172 (2006)Cite this article

Abstract

The developmental and evolutionary mechanisms behind the emergence of human-specific brain features remain largely unknown. However, the recent ability to compare our genome to that of our closest relative, the chimpanzee, provides new avenues to link genetic and phenotypic changes in the evolution of the human brain. We devised a ranking of regions in the human genome that show significant evolutionary acceleration. Here we report that the most dramatic of these ‘human accelerated regions’, HAR1, is part of a novel RNA gene (HAR1F) that is expressed specifically in Cajal–Retzius neurons in the developing human neocortex from 7 to 19 gestational weeks, a crucial period for cortical neuron specification and migration. HAR1F is co-expressed with reelin, a product of Cajal–Retzius neurons that is of fundamental importance in specifying the six-layer structure of the human cortex. HAR1 and the other human accelerated regions provide new candidates in the search for uniquely human biology.

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Figure 1: HAR1-associated transcripts in genomic context.
Figure 2: Predicted RNA secondary structure for HAR1F.
Figure 3: Expression of HAR1F and HAR1R in the developing neocortex.
Figure 4: Expression of HAR1F in other parts of the developing brain.

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Acknowledgements

We thank G. Bejerano, C. Lowe, J. Kent, H. Noller, D. Feldheim, A. Love (UCSC), V. Albert and J.-C. Noel (Erasme Hospital), J.-P. Brion (ULB), A. Goffinet (UCL Louvain), the UCSC Genome Browser Group, Webb Miller (Penn. State), the Macaque Genome Sequencing Consortium, and the Broad Institute Genome Sequencing Platform and Whole-Genome Assembly Team. This work was funded by the Howard Hughes Medical Institute (D.H., S.R.S. and B.K.), the US NHGRI (D.H., A.D.K., S.K. and C.O.), the US National Cancer Institute (J.S.P.), the US NIGMS (K.S.P. and M.A.), the University of California Biotechnology Research and Education Program (A.S.), the Danish Research Council (J.S.P.), the Belgian FNRS, the Belgian FRSM, the Belgian Queen Elizabeth Medical Foundation (FMRE), the Interuniversity Attraction Poles Programme, Belgian State and Federal Office for Scientific, Technical and Cultural Affairs (P.V.), and the Fondation Erasme (M.-A.L. and N.L.). P.V. and M.-A.L. are Research Associate and Research Fellow of the FNRS, respectively. Author Contributions Computational methods developed and applied by K.S.P., J.S.P., A.S. and A.D.K. Experimental analysis by S.R.S., P.V., N.L., M.-A.L., S.C., S.K., B.K., C.O., C.D., H.I. and M.A. Manuscript primarily written by K.S.P., S.R.S., P.V. and D.H.

Author information

Author notes

  1. Katherine S. Pollard & Adam Siepel

    Present address: Department of Statistics and UC Davis Genome Center, University of California, Davis, California, 95616, USA

  2. Katherine S. Pollard and Sofie R. Salama: *These authors contributed equally to this work

Authors and Affiliations

  1. Center for Biomolecular Science & Engineering,

    Katherine S. Pollard, Sofie R. Salama, Jakob S. Pedersen, Sol Katzman, Bryan King, Courtney Onodera, Adam Siepel, Andrew D. Kern & David Haussler

  2. Howard Hughes Medical Institute,

    Sofie R. Salama, Bryan King & David Haussler

  3. Center for Molecular Biology of RNA, Department of Molecular, Cell & Developmental Biology, University of California, Santa Cruz, California, 95064, USA

    Haller Igel & Manuel Ares Jr

  4. Developmental Biology, University of California,

    Haller Igel & Manuel Ares Jr

  5. Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Free University of Brussels (ULB),

    Nelle Lambert, Marie-Alexandra Lambot, Sandra Coppens & Pierre Vanderhaeghen

  6. Department of Psychiatry, Erasme Hospital, Free University of Brussels (ULB), B-1070, Brussels, Belgium

    Nelle Lambert

  7. INSERM, U371, Stem Cell & Brain Research Institute, F-69500, Bron cedex, France

    Colette Dehay

  8. Brain Research Institute, F-69500, Bron cedex

    Colette Dehay

  9. Université Claude Bernard, Lyon 1, F-69500, Bron cedex, France

    Adam Siepel & Colette Dehay

  10. Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, 14853, USA

    Adam Siepel

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Corresponding author

Correspondence to David Haussler.

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Competing interests

The sequences of the HAR1 transcripts reported in this study have been submitted to GenBank (accession numbers DQ860409–DQ860415). Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

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Pollard, K., Salama, S., Lambert, N. et al. An RNA gene expressed during cortical development evolved rapidly in humans. Nature 443, 167–172 (2006). https://doi.org/10.1038/nature05113

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