ArticlePLoS genetics2008
Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection.
Article in PLoS genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 67 citations in OpenAlex.
- Review
- Neanderthal and Denisovan Glutamate Dehydrogenase 2 Evolution and Clinical Significance.International journal of molecular sciences · 2025Article
- Evolution of retrocopies in the context of HUSH silencing.Biology direct · 2024Article
- Evolution of Glutamate Metabolism viaInternational journal of molecular sciences · 2024Review
- Evolutionary Changes in Primate Glutamate Dehydrogenases 1 and 2 Influence the Protein Regulation by Ligands, Targeting and Posttranslational Modifications.International journal of molecular sciences · 2024Review
- Bioinformatics analysis identifies GLUD1 as a prognostic indicator for clear cell renal cell carcinoma.European journal of medical research · 2024Article
- Article
- An integrative understanding of comparative cognition: lessons from human brain evolution.Integrative and comparative biology · 2020Review
- Haploid selection drives new gene male germline expression.Genome research · 2019Article
- Transgenic Mice Carrying GLUD2 as a Tool for Studying the Expressional and the Functional Adaptation of this Positive Selected Gene in Human Brain Evolution.Neurochemical research · 2019Article
- Localization of Human Glutamate Dehydrogenases Provides Insights into Their Metabolic Role and Their Involvement in Disease Processes.Neurochemical research · 2019Review
- Adaptive Evolution of the GDH2 Allosteric Domain Promotes Gliomagenesis by Resolving IDH1Cancer research · 2018Article
- The Genomic Impact of Gene Retrocopies: What Have We Learned from Comparative Genomics, Population Genomics, and Transcriptomic Analyses?Genome biology and evolution · 2017Article
- The Glutamate Dehydrogenase Pathway and Its Roles in Cell and Tissue Biology in Health and Disease.Biology · 2017Review
- Multiple Forms of Glutamate Dehydrogenase in Animals: Structural Determinants and Physiological Implications.Biology · 2016Review
- Evolution of GLUD2 Glutamate Dehydrogenase Allows Expression in Human Cortical Neurons.Molecular neurobiology · 2016Article
- Import of a major mitochondrial enzyme depends on synergy between two distinct helices of its presequence.The Biochemical journal · 2016Article
- Mice carrying a human GLUD2 gene recapitulate aspects of human transcriptome and metabolome development.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- The life history of retrocopies illuminates the evolution of new mammalian genes.Genome research · 2016Article
- The Mechanism Research of Qishen Yiqi Formula by Module-Network Analysis.Evidence-based complementary and alternative medicine : eCAM · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.