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MBE Advance Access published online on May 10, 2006
Molecular Biology and Evolution, doi:10.1093/molbev/msl012
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© The Author 2006. 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
Accepted May 9, 2006

Research Article

Cytosine Usage Modulates the Correlation Between CDS Length and CG Content in Prokaryotic Genomes

Xuhua Xia 1 *, Huaichun Wang 2, Zheng Xie 3, Malisa Carullo 3, Huang Huang 3, and Donal Hickey 4

1 Department of Biology, University of Ottawa, 30 Marie Curie, P.O. Box 450, Station A, Ottawa, Ontario, Canada, K1N 6N5. Tel: (613) 562-5800 ext. 6886, Fax: (613) 562-5486; Center for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, Canada, K1N 6N5
2 Department of Mathematics and Statistics, Dalhousie University, Halifax, Nova Scotia, B3H 3J5
3 Department of Biology, University of Ottawa, 30 Marie Curie, P.O. Box 450, Station A, Ottawa, Ontario, Canada, K1N 6N5. Tel: (613) 562-5800 ext. 6886, Fax: (613) 562-5486
4 Biology Department, Concordia University, 7141 Sherbrooke West, Montreal, Quebec, Canada H4B 1R6

* To whom correspondence should be addressed.
Xuhua Xia, E-mail: xxia{at}uottawa.ca


  Abstract

Previous studies have argued that, given the AT-rich nature of stop codons, the length and CG% of coding sequences (CDSs) should be positively correlated. This prediction is generally supported empirically by prokaryotic genomes. However, the correlation is weak for a number of species, with four species showing a negative correlation. Here we formulate a more general hypothesis incorporating selection against cytosine usage to explain the lack of strong positive correlation between the length and GC% of CDSs. Two factors contribute to the selection against cytosine (C) usage in long coding sequences. First, C is the least abundant nucleotide in the cell and a long coding sequence should have fewer Cs to increase transcription efficiency. Second, C is prone to mutation to U/T and selection for increased reliability should reduce C usage in long CDSs. Empirical data from prokaryotic genomes lend strong support for this new hypothesis.

Keywords: selection against cytosine; differential nucleotide availability; genomic evolution; CDS length; CG content.
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