Mechanisms and convergence of compensatory evolution in mammalian mitochondrial tRNAs

A. Kern, F. Kondrashov, Nature Genetics 36 (2004) 1207–1212.

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Abstract
The function of protein and RNA molecules depends on complex epistatic interactions between sites. Therefore, the deleterious effect of a mutation can be suppressed by a compensatory second-site substitution. In relating a list of 86 pathogenic mutations in human IRNAs encoded by mitochondrial genes to the sequences of their mammalian orthologs, we noted that 52 pathogenic mutations were present in normal tRNAs of one or several nonhuman mammals. We found at least five mechanisms of compensation for 32 pathogenic mutations that destroyed a Watson-Crick pair in one of the four tRNA stems: restoration of the affected Watson-Crick interaction (25 cases), strengthening of another pair (4 cases), creation of a new pair (8 cases), changes of multiple interactions in the affected stem (11 cases) and changes involving the interaction between the loop and stem structures (3 cases). A pathogenic mutation and its compensating substitution are fixed in a lineage in rapid succession, and often a compensatory interaction evolves convergently in different clades. At least 10%, and perhaps as many as 50%, of all nucleotide substitutions in evolving mammalian (RNAs participate in such interactions, indicating that the evolution of tRNAs proceeds along highly epistatic fitness ridges.
Publishing Year
Date Published
2004-11-01
Journal Title
Nature Genetics
Acknowledgement
We thank J. Gillespie, M. Hahn, L. Horth, A. Kondrashov, A. Kopp, S. Nuzhdin, M. Turelli and D. Weinreich for their contributions. The authors were supported by a grant from the US National Institutes of Health to S. Nuzhdin, and A.D.K. is a Howard Hughes
Volume
36
Issue
11
Page
1207 - 1212
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Kern A, Kondrashov F. Mechanisms and convergence of compensatory evolution in mammalian mitochondrial tRNAs. Nature Genetics. 2004;36(11):1207-1212. doi:10.1038/ng1451
Kern, A., & Kondrashov, F. (2004). Mechanisms and convergence of compensatory evolution in mammalian mitochondrial tRNAs. Nature Genetics, 36(11), 1207–1212. https://doi.org/10.1038/ng1451
Kern, Andrew, and Fyodor Kondrashov. “Mechanisms and Convergence of Compensatory Evolution in Mammalian Mitochondrial TRNAs.” Nature Genetics 36, no. 11 (2004): 1207–12. https://doi.org/10.1038/ng1451.
A. Kern and F. Kondrashov, “Mechanisms and convergence of compensatory evolution in mammalian mitochondrial tRNAs,” Nature Genetics, vol. 36, no. 11, pp. 1207–1212, 2004.
Kern A, Kondrashov F. 2004. Mechanisms and convergence of compensatory evolution in mammalian mitochondrial tRNAs. Nature Genetics. 36(11), 1207–1212.
Kern, Andrew, and Fyodor Kondrashov. “Mechanisms and Convergence of Compensatory Evolution in Mammalian Mitochondrial TRNAs.” Nature Genetics, vol. 36, no. 11, Nature Publishing Group, 2004, pp. 1207–12, doi:10.1038/ng1451.

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