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Tertiary Windowing to Detect Positive Diversifying Selection

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Abstract

As a protein-encoding gene evolves, different selective pressures act on the gene temporally and spatially. An examination of the ratio of nonsynonymous-to-synonymous nucleotide substitution rate ratios (Ka/Ks) has proven to be a valuable method to examine selective pressures on protein encoding genes, including detecting positive diversifying selection. To gain power over averaging all sites in a gene together, examination of sites in primary sequence windows has frequently been employed. However, selection acts on folded proteins and sites that are close in tertiary space may not be close in primary sequence. A new method for the examination of Ka/Ks ratios based upon windows in tertiary structure is introduced and applied to the leptin gene family in mammals. Tertiary sequence windowing detects new sites under positive diversifying selection and detects positive diversifying selection with a more significant signal along various branches of the leptin gene family tree.

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Acknowledgments

We thank Erik Sonnhammer for helpful discussions on methodology. Funding and support for this project were provided by the Swedish Foundation for Strategic Research, Vetenskapsrådet, and FUGE, the Norwegian National Functional Genomics Platform.

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Authors and Affiliations

  1. Computational Biology Unit, BCCS, University of Bergen, 5020, Bergen, Norway

    Ann-Charlotte Berglund & David A. Liberles

  2. Stockholm Bioinformatics Center, SCFAB, Stockholm University, 10691, Stockholm, Sweden

    Ann-Charlotte Berglund, Björn Wallner, Arne Elofsson & David A. Liberles

Authors
  1. Ann-Charlotte Berglund
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  2. Björn Wallner
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  3. Arne Elofsson
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  4. David A. Liberles
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Correspondence to David A. Liberles.

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Reviewing Editor: Dr. Rasmus Nielsen

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Berglund, AC., Wallner, B., Elofsson, A. et al. Tertiary Windowing to Detect Positive Diversifying Selection. J Mol Evol 60, 499–504 (2005). https://doi.org/10.1007/s00239-004-0223-4

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  • DOI: https://doi.org/10.1007/s00239-004-0223-4

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