Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness

M. Meer, A. Kondrashov, Y. Artzy Randrup, F. Kondrashov, Nature 464 (2010) 279–282.

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Abstract
A long-standing controversy in evolutionary biology is whether or not evolving lineages can cross valleys on the fitness landscape that correspond to low-fitness genotypes, which can eventually enable them to reach isolated fitness peaks1-9. Here we study the fitness landscapes traversed by switches between different AU and GC Watson-Crick nucleotide pairs at complementary sites of mitochondrial transfer RNA stem regions in 83 mammalian species. We find that such Watson-Crick switches occur 30-40 times more slowly than pairs of neutral substitutions, and that alleles corresponding to GU and AC non-Watson-Crick intermediate states segregate within human populations at low frequencies, similar to those of non-synonymous alleles. Substitutions leading to a Watson-Crick switch are strongly correlated, especially in mitochondrial tRNAs encoded on the GT-nucleotide-rich strand of the mitochondrial genome. Using these data we estimate that a typical Watson-Crick switch involves crossing a fitness valley of a depth of about 10-3 or even about 10-2, with AC intermediates being slightly more deleterious than GU intermediates. This compensatory evolution must proceed through rare intermediate variants that never reach fixation. The ubiquitous nature of compensatory evolution in mammalian mitochondrial tRNAs and other molecules implies that simultaneous fixation of two alleles that are individually deleterious may be a common phenomenon at the molecular level.
Publishing Year
Date Published
2010-03-11
Journal Title
Nature
Acknowledgement
We thank H. Innan, M. Laessig, R. Guigo, I. Povolotskaya, D. Ivankov and M. Breen for thoughtful discussions and critical reading of the manuscript.
Volume
464
Issue
7286
Page
279 - 282
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Meer M, Kondrashov A, Artzy Randrup Y, Kondrashov F. Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness. Nature. 2010;464(7286):279-282. doi:10.1038/nature08691
Meer, M., Kondrashov, A., Artzy Randrup, Y., & Kondrashov, F. (2010). Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness. Nature, 464(7286), 279–282. https://doi.org/10.1038/nature08691
Meer, Margarita, Alexey Kondrashov, Yael Artzy Randrup, and Fyodor Kondrashov. “Compensatory Evolution in Mitochondrial TRNAs Navigates Valleys of Low Fitness.” Nature 464, no. 7286 (2010): 279–82. https://doi.org/10.1038/nature08691.
M. Meer, A. Kondrashov, Y. Artzy Randrup, and F. Kondrashov, “Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness,” Nature, vol. 464, no. 7286, pp. 279–282, 2010.
Meer M, Kondrashov A, Artzy Randrup Y, Kondrashov F. 2010. Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness. Nature. 464(7286), 279–282.
Meer, Margarita, et al. “Compensatory Evolution in Mitochondrial TRNAs Navigates Valleys of Low Fitness.” Nature, vol. 464, no. 7286, Nature Publishing Group, 2010, pp. 279–82, doi:10.1038/nature08691.

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