The identification and functional implications of human-specific "fixed" amino acid substitutions in the glutamate receptor family

Hiroki Goto, Kazunori Watanabe, Naozumi Araragi, Rui Kageyama, Kunika Tanaka, Yoko Kuroki, Atsushi Toyoda, Masahira Hattori, Yoshiyuki Sakaki, Asao Fujiyama, Yasuyuki Fukumaki, Hiroki Shibata

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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/KSratios 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.

Original languageEnglish
Article number224
JournalBMC Evolutionary Biology
Volume9
Issue number1
DOIs
Publication statusPublished - 2009
Externally publishedYes

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amino acid substitution
substitution
amino acid
gene
Pan troglodytes
genes
divergence
common ancestry
nervous system
family
glutamate receptors
structural change
brain
synaptic transmission
Pongidae
protein
central nervous system
ancestry

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics

Cite this

The identification and functional implications of human-specific "fixed" amino acid substitutions in the glutamate receptor family. / Goto, Hiroki; Watanabe, Kazunori; Araragi, Naozumi; Kageyama, Rui; Tanaka, Kunika; Kuroki, Yoko; Toyoda, Atsushi; Hattori, Masahira; Sakaki, Yoshiyuki; Fujiyama, Asao; Fukumaki, Yasuyuki; Shibata, Hiroki.

In: BMC Evolutionary Biology, Vol. 9, No. 1, 224, 2009.

Research output: Contribution to journalArticle

Goto, H, Watanabe, K, Araragi, N, Kageyama, R, Tanaka, K, Kuroki, Y, Toyoda, A, Hattori, M, Sakaki, Y, Fujiyama, A, Fukumaki, Y & Shibata, H 2009, 'The identification and functional implications of human-specific "fixed" amino acid substitutions in the glutamate receptor family', BMC Evolutionary Biology, vol. 9, no. 1, 224. https://doi.org/10.1186/1471-2148-9-224
Goto, Hiroki ; Watanabe, Kazunori ; Araragi, Naozumi ; Kageyama, Rui ; Tanaka, Kunika ; Kuroki, Yoko ; Toyoda, Atsushi ; Hattori, Masahira ; Sakaki, Yoshiyuki ; Fujiyama, Asao ; Fukumaki, Yasuyuki ; Shibata, Hiroki. / The identification and functional implications of human-specific "fixed" amino acid substitutions in the glutamate receptor family. In: BMC Evolutionary Biology. 2009 ; Vol. 9, No. 1.
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AU - Toyoda, Atsushi

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