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Global discovery of adaptive mutations

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Abstract

Although modern DNA sequencing enables rapid identification of genetic variation, characterizing the phenotypic consequences of individual mutations remains a labor-intensive task. Here we describe array-based discovery of adaptive mutations (ADAM), a technology that searches an entire bacterial genome for mutations that contribute to selectable phenotypic variation between an evolved strain and its parent. We found that ADAM identified adaptive mutations in laboratory-evolved Escherichia coli strains with high sensitivity and specificity.

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Figure 1: Array-based discovery of adaptive mutations.
Figure 2: Using ADAM to identify known and new mutations.
Figure 3: Validation of discovered mutations in ASN*.

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Acknowledgements

We thank J. Liu for assistance in creating the ASN* strain. A.K.H. was supported by fellowship #08-1090-CCR-EO from the New Jersey Commission on Cancer Research. S.T. was supported by grants from the National Science Foundation Career Award (CAREER), Defense Advanced Research Projects Agency, National Institute of General Medical Sciences (P50 GM071508) and the National Institutes of Health Director's Pioneer Award (1DP10D003787-01).

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Author notes

  1. Hani Goodarzi and Alison K Hottes: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Biology & Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA

    Hani Goodarzi, Alison K Hottes & Saeed Tavazoie

Authors
  1. Hani Goodarzi
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  2. Alison K Hottes
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  3. Saeed Tavazoie
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Contributions

H.G. conceived and designed the approach, performed experiments, analyzed the data and wrote the paper; A.K.H. performed experiments, analyzed the data and wrote the paper; S.T. wrote the paper.

Corresponding author

Correspondence to Saeed Tavazoie.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6, Supplementary Tables 1–5 and Supplementary Note 1 (PDF 1763 kb)

Supplementary Software 1

ADAM computational tools (ZIP 3911 kb)

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Goodarzi, H., Hottes, A. & Tavazoie, S. Global discovery of adaptive mutations. Nat Methods 6, 581–583 (2009). https://doi.org/10.1038/nmeth.1352

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  • DOI: https://doi.org/10.1038/nmeth.1352

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