ArticleNature2010
Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness.
Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed.
- How Does Transcription-Associated Mutagenesis Shape tRNA Microevolution?Genome biology and evolution · 2026Article
- Sign Epistasis Can be Absent in Multi-peaked Landscapes With Neutral Mutations.Genome biology and evolution · 2026Article
- Mitogenomic analysis ofFrontiers in veterinary science · 2026Article
- Addressing epistasis in the design of protein function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mutation pressure, drift, and the pace of molecular coevolution.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Template switching in DNA replication can create and maintain RNA hairpins.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Comparative Mitogenomics inGenes · 2021Article
- Adenine·cytosine substitutions are an alternative pathway of compensatory mutation in angiosperm ITS2.RNA (New York, N.Y.) · 2020Article
- Article
- Article
- Compensatory mutations and epistasis for protein function.Current opinion in structural biology · 2018Review
- Slightly deleterious genomic variants and transcriptome perturbations in Down syndrome embryonic selection.Genome research · 2018Article
- Evolution of complex adaptations in molecular systems.Nature ecology & evolution · 2017Article
- Short template switch events explain mutation clusters in the human genome.Genome research · 2017Article
- Stability-Mediated Epistasis Restricts Accessible Mutational Pathways in the Functional Evolution of Avian Hemoglobin.Molecular biology and evolution · 2017Article
- Compensatory Evolution of Intrinsic Transcription Terminators in Bacillus Cereus.Genome biology and evolution · 2017Article
- Network of epistatic interactions within a yeast snoRNA.Science (New York, N.Y.) · 2016Article
- The fitness landscape of a tRNA gene.Science (New York, N.Y.) · 2016Article
- Article
- Breaking evolutionary constraint with a tradeoff ratchet.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
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 peaks. 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.