Open Access Research article

Context dependent substitution biases vary within the human genome

P Andrew Nevarez12, Christopher M DeBoever13, Benjamin J Freeland1, Marissa A Quitt14 and Eliot C Bush1*

Author Affiliations

1 Department of Biology, Harvey Mudd College, Claremont, CA, USA

2 Department of Biology, Duke University, Durham, NC, USA

3 Division of Biological Sciences, University of California San Diego, La Jolla, CA, USA

4 Division of Biology, California Institute of Technology, Pasadena, CA, USA

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BMC Bioinformatics 2010, 11:462  doi:10.1186/1471-2105-11-462

Published: 15 September 2010



Models of sequence evolution typically assume that different nucleotide positions evolve independently. This assumption is widely appreciated to be an over-simplification. The best known violations involve biases due to adjacent nucleotides. There have also been suggestions that biases exist at larger scales, however this possibility has not been systematically explored.


To address this we have developed a method which identifies over- and under-represented substitution patterns and assesses their overall impact on the evolution of genome composition. Our method is designed to account for biases at smaller pattern sizes, removing their effects. We used this method to investigate context bias in the human lineage after the divergence from chimpanzee. We examined bias effects in substitution patterns between 2 and 5 bp long and found significant effects at all sizes. This included some individual three and four base pair patterns with relatively large biases. We also found that bias effects vary across the genome, differing between transposons and non-transposons, between different classes of transposons, and also near and far from genes.


We found that nucleotides beyond the immediately adjacent one are responsible for substantial context effects, and that these biases vary across the genome.