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MBE Advance Access published online on July 23, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm151
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Published by Oxford University Press 2007.

Research Article

A Sequence-based Model Accounts Largely for the Relationship of Intron Positions to Protein Structural Features

Danny W. De Kee1, Vivek Gopalan1 and Arlin Stoltzfus1,2

1 Center for Advanced Research in Biotechnology, Rockville, MD 20850, tel: 240-314-6000 fax: 240-314-6255, DWD: Email: dan.dekee{at}gmail.com, VG Email: gopalan{at}umbi.umd.edu

2 Corresponding Author, Email: stoltzfu{at}umbi.umd.edu

Received for publication March 11, 2007. Revision received June 21, 2007. Accepted for publication June 25, 2007.

Claims of intron-structure correlations have played a major role in debates surrounding split gene origins. In the formative (as opposed to disruptive or "insertional") model of split gene origins, introns represent the scars of chimaeric gene assembly. When analyzed retrospectively, formative introns should tend to fall between modular units, if such units exist, or at least to exhibit a preference for sites favorable to chimaera formation. However, there is another possible source of preferences: under a disruptive model of split gene origins, fortuitous intron-structure correlations may arise because the gain of introns is biased with respect to flanking nucleotide sequences. To investigate the extent to which a sequence-biased intron gain model may account for the present-day distribution of introns, data on over 10000 introns in eukaryotic protein-coding genes were integrated with structural data from a set of 1851 non-redundant protein chains. The positions of introns with respect to secondary structures, solvent accessibility, and so-called "modules" were evaluated relative to the expectations of a null model, a disruptive model based on amino acid frequencies at splice junctions, and a formative model defined relative to these. The null model can be excluded for most structural features, and is highly improbable when intron sites are grouped by reading frame phase. Phase-dependent correlations with secondary structure and side-chain surface accessibility are particularly strong. However, these phase-dependent correlations are explained largely by the sequence-based disruptive model.

Key Words: intron evolution • secondary structure • sequence preferences • splice site


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