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J Mol Evol. 2012 Jun;74(5-6):332-41. doi: 10.1007/s00239-012-9510-7. Epub 2012 Jun 30.

Mutational bias plays an important role in shaping longevity-related amino acid content in mammalian mtDNA-encoded proteins.

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  • 1Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, 29071 Málaga, Spain.


During the course of evolution, amino acid shifts might have resulted in mitochondrial proteomes better endowed to resist oxidative stress. However, owing to the problem of distinguishing between functional constraints/adaptations in protein sequences and mutation-driven biases in the composition of these sequences, the adaptive value of such amino acid shifts remains under discussion. We have analyzed the coding sequences of mtDNA from 173 mammalian species, dissecting the effect of nucleotide composition on amino acid usages. We found remarkable cysteine avoidance in mtDNA-encoded proteins. However, no effect of longevity on cysteine content could be detected. On the other hand, nucleotide compositional shifts fully accounted for threonine usages. In spite of a strong effect of mutational bias on methionine abundances, our results suggest a role of selection in determining the composition of methionine. Whether this selective effect is linked or not to protection against oxidative stress is still a subject of debate.

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