Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection.

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Version: Final published version
Serval ID
serval:BIB_104508EF3F21
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection.
Journal
PLoS Genetics
Author(s)
Rosso L., Marques A.C., Reichert A.S., Kaessmann H.
ISSN
1553-7404[electronic]
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
4
Number
8
Pages
e1000150
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: epublish
Abstract
Many new gene copies emerged by gene duplication in hominoids, but little is known with respect to their functional evolution. Glutamate dehydrogenase (GLUD) is an enzyme central to the glutamate and energy metabolism of the cell. In addition to the single, GLUD-encoding gene present in all mammals (GLUD1), humans and apes acquired a second GLUD gene (GLUD2) through retroduplication of GLUD1, which codes for an enzyme with unique, potentially brain-adapted properties. Here we show that whereas the GLUD1 parental protein localizes to mitochondria and the cytoplasm, GLUD2 is specifically targeted to mitochondria. Using evolutionary analysis and resurrected ancestral protein variants, we demonstrate that the enhanced mitochondrial targeting specificity of GLUD2 is due to a single positively selected glutamic acid-to-lysine substitution, which was fixed in the N-terminal mitochondrial targeting sequence (MTS) of GLUD2 soon after the duplication event in the hominoid ancestor approximately 18-25 million years ago. This MTS substitution arose in parallel with two crucial adaptive amino acid changes in the enzyme and likely contributed to the functional adaptation of GLUD2 to the glutamate metabolism of the hominoid brain and other tissues. We suggest that rapid, selectively driven subcellular adaptation, as exemplified by GLUD2, represents a common route underlying the emergence of new gene functions.
Keywords
Amino Acid Sequence, Amino Acid Substitution, Animals, Arabidopsis Proteins/chemistry, Arabidopsis Proteins/genetics, Cell Line, Cercopithecus aethiops, Evolution, Molecular, Gene Duplication, Glutamate Dehydrogenase/chemistry, Glutamate Dehydrogenase/genetics, Glutamate Dehydrogenase (NADP+)/chemistry, Glutamate Dehydrogenase (NADP+)/genetics, Hominidae/genetics, Hominidae/metabolism, Humans, Hylobates, Mice, Mitochondria/chemistry, Mitochondria/enzymology, Molecular Sequence Data, Phylogeny, Protein Sorting Signals, Protein Transport, Selection, Genetic, Sequence Alignment, Species Specificity
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2009 22:13
Last modification date
20/08/2019 12:37
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