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Adaptive threonine increase in transmembrane regions of mitochondrial proteins in higher primates.

Kitazoe Y, Kishino H, Hasegawa M, Nakajima N, Thorne JL, Tanaka M - PLoS ONE (2008)

Bottom Line: This Thr increase involved the replacement of hydrophobic AAs in the membrane interior.Because crucial roles of Thr and Ser in membrane proteins have been proposed to be the formation of hydrogen bonds enhancing helix-helix interactions, the Thr increase detected in the higher primates might be adaptive by serving to reinforce stability of mt proteins in the inner membrane.The correlation between Thr composition in the membrane interior and the longevity of animals is striking, especially because some mt functions are thought to be involved in aging.

View Article: PubMed Central - PubMed

Affiliation: Center of Medical Information Science, Kochi Medical School, Nankoku, Kochi, Japan. kitazoey@kochi-u.ac.jp

ABSTRACT

Background: The mitochondrial (mt) gene tree of placental mammals reveals a very strong acceleration of the amino acid (AA) replacement rate and a change in AA compositional bias in the lineage leading to the higher primates (simians), in contrast to the nuclear gene tree. Whether this acceleration and compositional bias were caused by adaptive evolution at the AA level or directional mutation pressure at the DNA level has been vigorously debated.

Methodology/principal findings: Our phylogenetic analysis indicates that the rate acceleration in the simian lineage is accompanied by a marked increase in threonine (Thr) residues in the transmembrane helix regions of mt DNA-encoded proteins. This Thr increase involved the replacement of hydrophobic AAs in the membrane interior. Even after accounting for lack of independence due to phylogeny, a regression analysis reveals a statistical significant positive correlation between Thr composition and longevity in primates.

Conclusion/significance: Because crucial roles of Thr and Ser in membrane proteins have been proposed to be the formation of hydrogen bonds enhancing helix-helix interactions, the Thr increase detected in the higher primates might be adaptive by serving to reinforce stability of mt proteins in the inner membrane. The correlation between Thr composition in the membrane interior and the longevity of animals is striking, especially because some mt functions are thought to be involved in aging.

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Related in: MedlinePlus

3-dimensional structure around Ile 78 position (helix B) in bovine Cytb.I78, Q57 and Y75 denote three AA positions of Ile 78 (helix B), Gln 57 (helix A) and Try 75 (helix B) in bovine Cytb, respectively.
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pone-0003343-g006: 3-dimensional structure around Ile 78 position (helix B) in bovine Cytb.I78, Q57 and Y75 denote three AA positions of Ile 78 (helix B), Gln 57 (helix A) and Try 75 (helix B) in bovine Cytb, respectively.

Mentions: We searched for AA positions at which putative helix-helix interactions could be formed by the change from Hoa to Thr, on the basis of the bovine crystal structure of respiratory complex III (cytochrome bc1 complex; PDB ID: 1QCR reported by Xia et al. [30]). We first looked at the AA position 78 in Cytb which gives Hoa (such as Ile, Leu, Met, and Val) in most of the 62 taxa of Figure 1. Among the 62 taxa, this position has Thr only in gorilla, baboon, and sperm whale. When Ile78 in the helix B of bovine Cytb is replaced by Thr, the Oγ atom of Thr78 has a possibility of forming a hydrogen bond with the Nε atom of Gln57 in the transmembrane, helix of Rieske iron-sulfur protein (Figure 6). This replacement is of particular interest, because we recently reported that the Ile78Thr replacement in Cytb was more frequently detected in Japanese semi-supercentenarians whose ages were 105 years and over, than in controls [31]. This Ile78Thr replacement in human individuals with extreme longevity may contribute to the stability of the respiratory complex by enhancing the helix-helix interaction within the molecule. The second example is the AA position 180 of Cytb which gives Thr in simians and sperm whale, and Ala in the remaining taxa except for cat with Gly. When Ala180 in helix D of bovine is replaced by Thr, this Thr180 can form a hydrogen bond with the main chain carbonyl group of Ala52 in helix A. The third example is the AA position 302 of Cytb which gives Thr in chimpanzee, orangutan and capuchin of simians, and Hoa in the remaining taxa. When Ala302 in helix F of bovine is replaced by Thr, this Thr302 can form a hydrogen bond with the side chain of Asn114 in helix C. Further detailed molecular simulations and experiments are needed to verify our proposal that the increase of Thr residues in higher primates is associated with an increased stability of mitochondrial proteins but the proposal is supported by our preliminary investigations (Table S2).


Adaptive threonine increase in transmembrane regions of mitochondrial proteins in higher primates.

Kitazoe Y, Kishino H, Hasegawa M, Nakajima N, Thorne JL, Tanaka M - PLoS ONE (2008)

3-dimensional structure around Ile 78 position (helix B) in bovine Cytb.I78, Q57 and Y75 denote three AA positions of Ile 78 (helix B), Gln 57 (helix A) and Try 75 (helix B) in bovine Cytb, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2553178&req=5

pone-0003343-g006: 3-dimensional structure around Ile 78 position (helix B) in bovine Cytb.I78, Q57 and Y75 denote three AA positions of Ile 78 (helix B), Gln 57 (helix A) and Try 75 (helix B) in bovine Cytb, respectively.
Mentions: We searched for AA positions at which putative helix-helix interactions could be formed by the change from Hoa to Thr, on the basis of the bovine crystal structure of respiratory complex III (cytochrome bc1 complex; PDB ID: 1QCR reported by Xia et al. [30]). We first looked at the AA position 78 in Cytb which gives Hoa (such as Ile, Leu, Met, and Val) in most of the 62 taxa of Figure 1. Among the 62 taxa, this position has Thr only in gorilla, baboon, and sperm whale. When Ile78 in the helix B of bovine Cytb is replaced by Thr, the Oγ atom of Thr78 has a possibility of forming a hydrogen bond with the Nε atom of Gln57 in the transmembrane, helix of Rieske iron-sulfur protein (Figure 6). This replacement is of particular interest, because we recently reported that the Ile78Thr replacement in Cytb was more frequently detected in Japanese semi-supercentenarians whose ages were 105 years and over, than in controls [31]. This Ile78Thr replacement in human individuals with extreme longevity may contribute to the stability of the respiratory complex by enhancing the helix-helix interaction within the molecule. The second example is the AA position 180 of Cytb which gives Thr in simians and sperm whale, and Ala in the remaining taxa except for cat with Gly. When Ala180 in helix D of bovine is replaced by Thr, this Thr180 can form a hydrogen bond with the main chain carbonyl group of Ala52 in helix A. The third example is the AA position 302 of Cytb which gives Thr in chimpanzee, orangutan and capuchin of simians, and Hoa in the remaining taxa. When Ala302 in helix F of bovine is replaced by Thr, this Thr302 can form a hydrogen bond with the side chain of Asn114 in helix C. Further detailed molecular simulations and experiments are needed to verify our proposal that the increase of Thr residues in higher primates is associated with an increased stability of mitochondrial proteins but the proposal is supported by our preliminary investigations (Table S2).

Bottom Line: This Thr increase involved the replacement of hydrophobic AAs in the membrane interior.Because crucial roles of Thr and Ser in membrane proteins have been proposed to be the formation of hydrogen bonds enhancing helix-helix interactions, the Thr increase detected in the higher primates might be adaptive by serving to reinforce stability of mt proteins in the inner membrane.The correlation between Thr composition in the membrane interior and the longevity of animals is striking, especially because some mt functions are thought to be involved in aging.

View Article: PubMed Central - PubMed

Affiliation: Center of Medical Information Science, Kochi Medical School, Nankoku, Kochi, Japan. kitazoey@kochi-u.ac.jp

ABSTRACT

Background: The mitochondrial (mt) gene tree of placental mammals reveals a very strong acceleration of the amino acid (AA) replacement rate and a change in AA compositional bias in the lineage leading to the higher primates (simians), in contrast to the nuclear gene tree. Whether this acceleration and compositional bias were caused by adaptive evolution at the AA level or directional mutation pressure at the DNA level has been vigorously debated.

Methodology/principal findings: Our phylogenetic analysis indicates that the rate acceleration in the simian lineage is accompanied by a marked increase in threonine (Thr) residues in the transmembrane helix regions of mt DNA-encoded proteins. This Thr increase involved the replacement of hydrophobic AAs in the membrane interior. Even after accounting for lack of independence due to phylogeny, a regression analysis reveals a statistical significant positive correlation between Thr composition and longevity in primates.

Conclusion/significance: Because crucial roles of Thr and Ser in membrane proteins have been proposed to be the formation of hydrogen bonds enhancing helix-helix interactions, the Thr increase detected in the higher primates might be adaptive by serving to reinforce stability of mt proteins in the inner membrane. The correlation between Thr composition in the membrane interior and the longevity of animals is striking, especially because some mt functions are thought to be involved in aging.

Show MeSH
Related in: MedlinePlus