The identification and functional implications of human-specific “fixed” amino acid substitutions in the glutamate receptor family
Open accessAbstract
BACKGROUND: The glutamate receptors (GluRs) play a vital role in the mediation of excitatory synaptic transmission in the central nervous system. To clarify the evolutionary dynamics and mechanisms of the GluR genes in the lineage leading to humans, we determined the complete sequences of the coding regions and splice sites of 26 chimpanzee GluR genes. RESULTS: We found that all of the reading frames and splice sites of these genes reported in humans were completely conserved in chimpanzees, suggesting that there were no gross structural changes in humans after their divergence from the human-chimpanzee common ancestor. We observed low KA/KS ratios in both humans and chimpanzees, and we found no evidence of accelerated evolution. We identified 30 human-specific "fixed" amino acid substitutions in the GluR genes by analyzing 80 human samples of seven different populations worldwide. Grantham's distance analysis showed that GRIN2C and GRIN3A are the most and the second most diverged GluR genes between humans and chimpanzees. However, most of the substitutions are non-radical and are not clustered in any particular region. Protein motif analysis assigned 11 out of these 30 substitutions to functional regions. Two out of these 11 substitutions, D71G in GRIN3A and R727H in GRIN3B, caused differences in the functional assignments of these genes between humans and other apes. CONCLUSION: We conclude that the GluR genes did not undergo drastic changes such as accelerated evolution in the human lineage after the divergence of chimpanzees. However, there remains a possibility that two human-specific "fixed" amino acid substitutions, D71G in GRIN3A and R727H in GRIN3B, are related to human-specific brain function.
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Synaptic proteins, including glutamate receptors, are rarely subject to extensive structural changes from one species to the next.
“Given their importance for the normal functioning of the organism, synaptic proteins, including glutamate receptors, are rarely subject to extensive structural changes from one species to the next (Bayés et al., 2011;Ryan and Grant, 2009;Goto et al., 2009;Wada et al., 2004).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Goto et al., 2009
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- Authors
- Goto, H., Watanabe, K., Araragi, N., Kageyama, R., Tanaka, K., Kuroki, Y., Toyoda, A., Hattori, M., Sakaki, Y., Fujiyama, A., Fukumaki, Y., & Shibata, H.
- Affiliations
- Kyushu University (JP)
- RIKEN Advanced Science Institute (JP)
- National Institute of Genetics (JP)
- The University of Tokyo (JP)
- RIKEN (JP)
- National Institute of Informatics (JP)
- Corresponding author
- Fukumaki, Yasuyuki
- ORCID
- Venue
- BMC Evolutionary Biology
- Published
- 2009-09-08
- Volume
- 9
- Issue
- 1
- Pages
- 224-224
- ISSN
- 1471-2148 (ISSN-L)
- PMC
- PMC2753569
- OpenAlex
- W2027246523
- Cited by
- 16
- References
- 39
- Citations by year
- 2025: 2 · 2023: 1 · 2022: 1 · 2019: 1 · 2017: 1 · 2013: 3 · 2012: 6
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Evolutionary Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
- Kyushu University Institutional Repository (QIR) (Kyushu University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Naito Foundation
- Directorate for Biological Sciences
- Japan Society for the Promotion of Science
- RIKEN
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- glutamate receptors, human-chimpanzee divergence, GRIN3A, evolutionary rates, dN/dS ratio, excitatory synaptic transmission
- MeSH terms
- Animals, Pan troglodytes, Multigene Family, Humans, Selection, Genetic, Genome, Human, Open Reading Frames, Sequence Analysis, DNA, Receptors, Glutamate, Evolution, Molecular, Amino Acid Substitution, RNA Splice Sites, Comparative Genomic Hybridization
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