Nature 443, 167-172 (14 September 2006) | doi:10.1038/nature05113; Received 27 June 2006; Accepted 25 July 2006; Published online 16 August 2006

An RNA gene expressed during cortical development evolved rapidly in humans

Katherine S. Pollard1,8,9, Sofie R. Salama1,2,9, Nelle Lambert4,5, Marie-Alexandra Lambot4, Sandra Coppens4, Jakob S. Pedersen1, Sol Katzman1, Bryan King1,2, Courtney Onodera1, Adam Siepel1,7, Andrew D. Kern1, Colette Dehay6,7, Haller Igel3, Manuel Ares, Jr3, Pierre Vanderhaeghen4 and David Haussler1,2

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.

  1. Center for Biomolecular Science & Engineering,
  2. Howard Hughes Medical Institute, and
  3. Center for Molecular Biology of RNA, Department of Molecular, Cell & Developmental Biology, University of California, Santa Cruz, California 95064, USA
  4. Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Free University of Brussels (ULB), and
  5. Department of Psychiatry, Erasme Hospital, Free University of Brussels (ULB), B-1070 Brussels, Belgium
  6. INSERM, U371, Stem Cell & Brain Research Institute, F-69500 Bron cedex, France
  7. Université Claude Bernard, Lyon 1, F-69500 Bron cedex, France
  8. †Present addresses: Department of Statistics and UC Davis Genome Center, University of California, Davis, California 95616, USA (K.S.P.); Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14853, USA (A.S.)
  9. *These authors contributed equally to this work

Correspondence to: David Haussler1,2 Correspondence and requests for materials should be addressed to D.H. (Email: The sequences of the HAR1 transcripts reported in this study have been submitted to GenBank (accession numbers DQ860409–DQ860415).


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Reelin and brain development

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