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Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness

Nature volume 464, pages 279–282 (2010)Cite this article

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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 peaks1,2,3,4,5,6,7,8,9. 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 fixation2. The ubiquitous nature of compensatory evolution in mammalian mitochondrial tRNAs and other molecules10,11 implies that simultaneous fixation of two alleles that are individually deleterious may be a common phenomenon at the molecular level.

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Figure 1: Fitness landscapes resulting from an interaction between two complementary sites in an RNA stem structure.
Figure 2: Watson–Crick switches in mammalian mt-tRNAs.
Figure 3: Mutation strand bias in mammalian mitochondria.
Figure 4: Polymorphism frequency distribution of minor alleles in the human population.

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Acknowledgements

We thank H. Innan, M. Laessig, R. Guigo, I. Povolotskaya, D. Ivankov and M. Breen for thoughtful discussions and critical reading of the manuscript.

Author Contributions M.V.M., Y.A.R. and F.A.K. obtained the initial evolutionary and polymorphism data. A.S.K. and F.A.K. supplied the theoretical treatment of the primary data. F.A.K. designed the study. All authors participated in writing the paper.

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Authors and Affiliations

  1. Bioinformatics and Genomics Programme, Centre for Genomic Regulation, C/Dr Aiguader 88, Barcelona Biomedical Research Park Building, 08003 Barcelona, Spain ,

    Margarita V. Meer & Fyodor A. Kondrashov

  2. Evolutionary Biology and Ecology Department, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA,

    Alexey S. Kondrashov & Yael Artzy-Randrup

  3. Howard Hughes Medical Institute and Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan 49109, USA,

    Yael Artzy-Randrup

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  1. Margarita V. Meer
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Correspondence to Fyodor A. Kondrashov.

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Meer, M., Kondrashov, A., Artzy-Randrup, Y. et al. Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness. Nature 464, 279–282 (2010). https://doi.org/10.1038/nature08691

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