Abstract
The enzyme glutamate dehydrogenase (GDH) is important for recycling the chief excitatory neurotransmitter, glutamate, during neurotransmission. Human GDH exists in housekeeping and brain-specific isotypes encoded by the genes GLUD1 and GLUD2, respectively. Here we show that GLUD2 originated by retroposition from GLUD1 in the hominoid ancestor less than 23 million years ago. The amino acid changes responsible for the unique brain-specific properties of the enzyme derived from GLUD2 occurred during a period of positive selection after the duplication event.
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References
Hertz, L., Dringen, R., Schousboe, A. & Robinson, S.R. J. Neurosci. Res. 57, 417–428 (1999).
Sonnewald, U., Westergaard, N. & Schousboe, A. Glia 21, 56–63 (1997).
Plaitakis, A., Metaxari, M. & Shashidharan, P. J. Neurochem. 75, 1862–1869 (2000).
Plaitakis, A., Spanaki, C., Mastorodemos, V. & Zaganas, I. Neurochem. Int. 43, 401–410 (2003).
Burbaeva, G. et al. Prog. Neuropsychopharmacol. Biol. Psychiatry 27, 675–680 (2003).
Wan, M. & Francke, U. Am. J. Med. Genet. 78, 169–172 (1998).
Shashidharan, P. et al. J. Biol. Chem. 269, 16971–16976 (1994).
Zhang, Z., Carriero, N. & Gerstein, M. Trends Genet. 20, 62–67 (2004).
Goodman, M. et al. Mol. Phylogenet. Evol. 9, 585–598 (1998).
Li, W.H. Molecular Evolution: Roles of Mutation and Selection in Molecular Evolution (Sinauer Associates, Sunderland, Massachusetts, 1997).
Noback, C.R. & Montagna, W. The Primate Brain: The Evolution of Mental Genes (Meredith Corporation, New York, 1970).
Evans, P.D. et al. Hum. Mol. Genet. 13, 489–494 (2004).
Evans, P.D., Anderson, J.R., Vallender, E.J., Choi, S.S. & Lahn, B.T. Hum. Mol. Genet. 13, 1139–1145 (2004).
Caceres, M. et al. Proc. Natl. Acad. Sci. USA 100, 13030–13035 (2003).
Cavallaro, S. et al. Proc. Natl. Acad. Sci. USA 94, 9669–9673 (1997).
Acknowledgements
We thank I. Dupanloup and A. Marques for constructive discussions; E. Farmer, L. Keller, I. Sanders and W. Wahli for comments on the manuscript; and A. Reymond for comments on the manuscript and samples. This research was supported by funds available to H.K. from the Center for Integrative Genomics, University of Lausanne, and the Swiss National Science Foundation.
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Supplementary Fig. 1 (download PDF )
Alignment of the GLUD2 insertion site in all species carrying this gene with the corresponding genomic region of an African Green monkey (an Old World monkey, OWM). (PDF 25 kb)
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Burki, F., Kaessmann, H. Birth and adaptive evolution of a hominoid gene that supports high neurotransmitter flux. Nat Genet 36, 1061–1063 (2004). https://doi.org/10.1038/ng1431
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DOI: https://doi.org/10.1038/ng1431
