Abstract
BackgroundThe 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 FindingsOur 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/SignificanceBecause 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.
Highlights
Mitochondria supply most cellular energy and influence cell growth, human disease, and probably aging [1]
Decrease in hydrophobic amino acid (AA) and increase in Thr residues on the placental mammal tree We first report that the 12 mt protein-coding genes underwent, at an early stage of simian evolution, a net flow of AA
We find that the HoaRThr flow occurred especially in the hydrophobic region (S.0.6) of mt proteins (the frequency distribution of S-values gives the maximum at S = 0.6, whereas the remaining 11 AAs (Rma) except for hydrophobic AAs (Hoa) and Thr had no flow (Figure 3B and Table 1A)
Summary
Mitochondria supply most cellular energy and influence cell growth, human disease, and probably aging [1]. 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
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