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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

Correlation between the Thr/Cys compositions and the MLS in primates.The Thr-Log(MLS) and Cys-Log(MLS) correlations were estimated in the hydrophobic region (S>0.6) of 12 mt proteins (Table 3 includes the results of the phylogenetic generalized least-squares for the regression analysis). The insertion gives the correlation coefficients (R) and the P-values for significance. The magnitude (R = 0.597, P = 0.004) of the Thr-Log(MLS) correlation (Figure A) was compatible with that (R = 0.619, P = 0.002) of the Cys-Log(MLS) (Figure B). Human was excluded in the analysis, since it became an outlier with a larger deviation than 3σ from the regression line (σ; the standard deviation) and indeed the MLS value (122.5 years) of human seems to be too large.
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pone-0003343-g005: Correlation between the Thr/Cys compositions and the MLS in primates.The Thr-Log(MLS) and Cys-Log(MLS) correlations were estimated in the hydrophobic region (S>0.6) of 12 mt proteins (Table 3 includes the results of the phylogenetic generalized least-squares for the regression analysis). The insertion gives the correlation coefficients (R) and the P-values for significance. The magnitude (R = 0.597, P = 0.004) of the Thr-Log(MLS) correlation (Figure A) was compatible with that (R = 0.619, P = 0.002) of the Cys-Log(MLS) (Figure B). Human was excluded in the analysis, since it became an outlier with a larger deviation than 3σ from the regression line (σ; the standard deviation) and indeed the MLS value (122.5 years) of human seems to be too large.

Mentions: We showed that the frequency of Thr residues greatly increased in the highly hydrophobic region (S>0.6) of mt proteins in the simians (Figure 3B and Table 1A). We speculate that this threonine increase may be related to life span via an increased stability of these proteins. Recently, Moosmann and Behl noted that Cys composition is negatively correlated with life span in a wide range of animals [26]. They argue that Cys depletion may render mt proteins more resistant to oxidative attack. By adding several taxa recently stored in the NCBI database [http://www.ncbi.nlm.nih.gov/Genbank/] and then calculating the Cys and Thr compositions (%) of primate AA sequences, we characterized the correlations between these AA compositions and the logarithm of maximum life spans (MLS). This was done by using phylogenetic generalized least-squares [27] because it takes into account the effect of tree structure within a multivariate regression framework (Materials and Methods; Table 3). A significant relationship between Thr composition and the logarithm of MLS appeared in primates where a predominant Hoa→Thr flow is observed (Figure 5A). Interestingly, the magnitude of this correlation was compatible with that of the Cys-Log (MLS) negative correlation (Figure 5B). The correlation was stronger in the hydrophobic region (S>0.6) of 4 proteins (ND1, ND2, ND4 and Cytb). Table S3 gives the values of Thr/Cys compositions and Log (MLS) in primates and the accession number of mt DNA sequences used in this analysis.


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)

Correlation between the Thr/Cys compositions and the MLS in primates.The Thr-Log(MLS) and Cys-Log(MLS) correlations were estimated in the hydrophobic region (S>0.6) of 12 mt proteins (Table 3 includes the results of the phylogenetic generalized least-squares for the regression analysis). The insertion gives the correlation coefficients (R) and the P-values for significance. The magnitude (R = 0.597, P = 0.004) of the Thr-Log(MLS) correlation (Figure A) was compatible with that (R = 0.619, P = 0.002) of the Cys-Log(MLS) (Figure B). Human was excluded in the analysis, since it became an outlier with a larger deviation than 3σ from the regression line (σ; the standard deviation) and indeed the MLS value (122.5 years) of human seems to be too large.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0003343-g005: Correlation between the Thr/Cys compositions and the MLS in primates.The Thr-Log(MLS) and Cys-Log(MLS) correlations were estimated in the hydrophobic region (S>0.6) of 12 mt proteins (Table 3 includes the results of the phylogenetic generalized least-squares for the regression analysis). The insertion gives the correlation coefficients (R) and the P-values for significance. The magnitude (R = 0.597, P = 0.004) of the Thr-Log(MLS) correlation (Figure A) was compatible with that (R = 0.619, P = 0.002) of the Cys-Log(MLS) (Figure B). Human was excluded in the analysis, since it became an outlier with a larger deviation than 3σ from the regression line (σ; the standard deviation) and indeed the MLS value (122.5 years) of human seems to be too large.
Mentions: We showed that the frequency of Thr residues greatly increased in the highly hydrophobic region (S>0.6) of mt proteins in the simians (Figure 3B and Table 1A). We speculate that this threonine increase may be related to life span via an increased stability of these proteins. Recently, Moosmann and Behl noted that Cys composition is negatively correlated with life span in a wide range of animals [26]. They argue that Cys depletion may render mt proteins more resistant to oxidative attack. By adding several taxa recently stored in the NCBI database [http://www.ncbi.nlm.nih.gov/Genbank/] and then calculating the Cys and Thr compositions (%) of primate AA sequences, we characterized the correlations between these AA compositions and the logarithm of maximum life spans (MLS). This was done by using phylogenetic generalized least-squares [27] because it takes into account the effect of tree structure within a multivariate regression framework (Materials and Methods; Table 3). A significant relationship between Thr composition and the logarithm of MLS appeared in primates where a predominant Hoa→Thr flow is observed (Figure 5A). Interestingly, the magnitude of this correlation was compatible with that of the Cys-Log (MLS) negative correlation (Figure 5B). The correlation was stronger in the hydrophobic region (S>0.6) of 4 proteins (ND1, ND2, ND4 and Cytb). Table S3 gives the values of Thr/Cys compositions and Log (MLS) in primates and the accession number of mt DNA sequences used in this analysis.

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