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DNA Research Advance Access published online on October 17, 2006
DNA Research, doi:10.1093/dnares/dsl007
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© The Author 2006. Kazusa DNA Research Institute.
Received January 31, 2006
Revised August 22, 2006

Short Communication

Negative Correlation of G+C Content at Silent Substitution Sites Between Orthologous Human and Mouse Protein-Coding Sequences

Naoki Takahashi 1 and Hiroshi Nakashima 1 *

1 Department of Clinical Laboratory Science, Graduate Course of Medical Science and Technology, Division of Health Science, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan

* To whom correspondence should be addressed.
Hiroshi Nakashima, E-mail: naka{at}kenroku.kanazawa-u.ac.jp


  Abstract

We conducted a genome-wide analysis of variations in guanine plus cytosine (G+C) content at the third codon position at silent substitution sites of orthologous human and mouse protein-coding nucleotide sequences. Alignments of 3776 human protein-coding DNA sequences with mouse orthologs having >50 synonymous codons were analyzed, and nucleotide substitutions were counted by comparing sequences in the alignments extracted from gap-free regions. The G+C content at silent sites in these pairs of genes showed a strong negative correlation (r = -0.93). Some gene pairs showed significant differences in G+C content at the third codon position at silent substitution sites. For example, human thymine-DNA glycosylase was A+T-rich at the silent substitution sites, while the orthologous mouse sequence was G+C-rich at the corresponding sites. In contrast, human matrix metalloproteinase 23B was G+C-rich at silent substitution sites, while the mouse ortholog was A+T-rich. We discuss possible implications of this significant negative correlation of G+C content at silent sites.

Keywords: G+C content variation; human-mouse orthologs; nucleotide substitutions in synonymous codons.
Communicated by Hiroyuki Toh
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