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Pairwise and higher-order genetic interactions during the evolution of a tRNA

Author

Listed:
  • Júlia Domingo

    (Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology)

  • Guillaume Diss

    (Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology)

  • Ben Lehner

    (Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology
    Universitat Pompeu Fabra (UPF)
    Institució Catalana de Recerca i Estudis Avançats (ICREA))

Abstract

A central question in genetics and evolution is the extent to which the outcomes of mutations change depending on the genetic context in which they occur1–3. Pairwise interactions between mutations have been systematically mapped within4–18 and between 19 genes, and have been shown to contribute substantially to phenotypic variation among individuals 20 . However, the extent to which genetic interactions themselves are stable or dynamic across genotypes is unclear21, 22. Here we quantify more than 45,000 genetic interactions between the same 87 pairs of mutations across more than 500 closely related genotypes of a yeast tRNA. Notably, all pairs of mutations interacted in at least 9% of genetic backgrounds and all pairs switched from interacting positively to interacting negatively in different genotypes (false discovery rate

Suggested Citation

  • Júlia Domingo & Guillaume Diss & Ben Lehner, 2018. "Pairwise and higher-order genetic interactions during the evolution of a tRNA," Nature, Nature, vol. 558(7708), pages 117-121, June.
    • Handle: RePEc:nat:nature:v:558:y:2018:i:7708:d:10.1038_s41586-018-0170-7
    DOI: 10.1038/s41586-018-0170-7
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    Cited by:

    1. Takahiro Nemoto & Tommaso Ocari & Arthur Planul & Muge Tekinsoy & Emilia A. Zin & Deniz Dalkara & Ulisse Ferrari, 2023. "ACIDES: on-line monitoring of forward genetic screens for protein engineering," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Solip Park & Fran Supek & Ben Lehner, 2021. "Higher order genetic interactions switch cancer genes from two-hit to one-hit drivers," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    3. Karol Buda & Charlotte M. Miton & Nobuhiko Tokuriki, 2023. "Pervasive epistasis exposes intramolecular networks in adaptive enzyme evolution," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Yeonwoo Park & Brian P. H. Metzger & Joseph W. Thornton, 2024. "The simplicity of protein sequence-function relationships," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Andreas Wagner, 2023. "Evolvability-enhancing mutations in the fitness landscapes of an RNA and a protein," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    6. Rachapun Rotrattanadumrong & Yohei Yokobayashi, 2022. "Experimental exploration of a ribozyme neutral network using evolutionary algorithm and deep learning," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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