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Deciphering polymorphism in 61,157 Escherichia coli genomes via epistatic sequence landscapes

Author

Listed:
  • Lucile Vigué

    (Université Paris Cité and Université Sorbonne Paris Nord, Inserm, IAME)

  • Giancarlo Croce

    (University of Lausanne
    Swiss Institute of Bioinformatics—SIB)

  • Marie Petitjean

    (Université Paris Cité and Université Sorbonne Paris Nord, Inserm, IAME)

  • Etienne Ruppé

    (Université Paris Cité and Université Sorbonne Paris Nord, Inserm, IAME
    Hôpital Bichat, APHP)

  • Olivier Tenaillon

    (Université Paris Cité and Université Sorbonne Paris Nord, Inserm, IAME)

  • Martin Weigt

    (Computational and Quantitative Biology—LCQB)

Abstract

Characterizing the effect of mutations is key to understand the evolution of protein sequences and to separate neutral amino-acid changes from deleterious ones. Epistatic interactions between residues can lead to a context dependence of mutation effects. Context dependence constrains the amino-acid changes that can contribute to polymorphism in the short term, and the ones that can accumulate between species in the long term. We use computational approaches to accurately predict the polymorphisms segregating in a panel of 61,157 Escherichia coli genomes from the analysis of distant homologues. By comparing a context-aware Direct-Coupling Analysis modelling to a non-epistatic approach, we show that the genetic context strongly constrains the tolerable amino acids in 30% to 50% of amino-acid sites. The study of more distant species suggests the gradual build-up of genetic context over long evolutionary timescales by the accumulation of small epistatic contributions.

Suggested Citation

  • Lucile Vigué & Giancarlo Croce & Marie Petitjean & Etienne Ruppé & Olivier Tenaillon & Martin Weigt, 2022. "Deciphering polymorphism in 61,157 Escherichia coli genomes via epistatic sequence landscapes," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31643-3
    DOI: 10.1038/s41467-022-31643-3
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    References listed on IDEAS

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    1. Michael S. Breen & Carsten Kemena & Peter K. Vlasov & Cedric Notredame & Fyodor A. Kondrashov, 2012. "Epistasis as the primary factor in molecular evolution," Nature, Nature, vol. 490(7421), pages 535-538, October.
    2. Jamie T. Bridgham & Eric A. Ortlund & Joseph W. Thornton, 2009. "An epistatic ratchet constrains the direction of glucocorticoid receptor evolution," Nature, Nature, vol. 461(7263), pages 515-519, September.
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