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MBE Advance Access published online on April 7, 2009
Molecular Biology and Evolution, doi:10.1093/molbev/msp071
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© The Author 2009. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

Strong Evidence for Lineage- and Sequence-Specificity of Substitution Rates and Patterns in Drosophila

Nadia D. Singh1,*, Peter F. Arndt2, Andrew G. Clark1 and Charles F. Aquadro1

1 Department of Molecular Biology and Genetics, Cornell University, Ithaca NY 14853
2 Max Planck Institute for Molecular Genetics, Ihnestr. 63/73, 14195 Berlin, Germany

* To whom correspondence should be addressed (nds25{at}cornell.edu)

Received for publication November 14, 2008. Revision received March 3, 2009. Revision received March 31, 2009. Accepted for publication April 1, 2009.

Rates of single nucleotide substitution in Drosophila are highly variable within the genome, and several examples illustrate that evolutionary rates differ among Drosophila species as well. Here we use a maximum-likelihood method to quantify lineage-specific substitutional patterns, and apply this method to 4-fold degenerate synonymous sites and introns from more than 8000 genes aligned in the D. melanogaster group. We find that within species, different classes of sequence evolve at different rates, with long introns evolving most slowly and short introns evolving most rapidly. . Relative rates of individual single nucleotide substitutions vary ~3-fold among lineages, yielding patterns of substitution that are comparatively less GC-biased in the melanogaster species complex relative to D. yakuba and D. erecta. These results are consistent with a model coupling a mutational shift towards reduced GC content, or a shift in mutation-selection balance, in the D. melanogaster species complex, with variation in selective constraint among different classes of DNA sequence. Finally, base composition of coding and intronic sequences is not at equilibrium with respect to substitutional patterns, which primarily reflects the slow rate of the substitutional process. These results thus support the view that mutational and/or selective processes are labile on an evolutionary timescale, and that if the process is indeed selection-driven, then the distribution of selective constraint is variable across the genome.

Key Words: Substitutional patterns • Drosophila • Stationary GC content • Selective constraint


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