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Background The pattern of point mutation is important for studying mutational mechanisms, genome evolution, and diseases. Previous studies of mutation direction were largely based on substitution data from a limited number of loci. To date, there is no genome-wide analysis of mutation direction or methylation-dependent transition rates in the chimpanzee or its categorized genomic regions.
Results In this study, we performed a detailed examination of mutation direction in the chimpanzee genome and its categorized genomic regions using 588,918 SNPs whose ancestral alleles could be inferred by mapping them to human genome sequences. The C→T (G→A) changes occurred most frequently in the chimpanzee genome. Each type of transition occurred approximately four times more frequently than each type of transversion. Notably, the frequency of C→T (G→A) was the highest in exons among the genomic categories regardless of whether we calculated directly, normalized with the nucleotide content, or removed the SNPs involved in the CpG effect. Moreover, the directionality of the point mutation in exons and CpG islands were opposite relative to their corresponding intergenic regions, indicating that different forces govern the nucleotide changes. Our analysis suggests that the GC content is not in equilibrium in the chimpanzee genome. Further quantitative analysis revealed that the 5-methylcytosine deamination rates at CpG sites were highly dependent on the local GC content and the lengths of SNP flanking sequences and varied among categorized genomic regions.
Conclusion We present the first mutational spectrum, estimated by three different approaches, in the chimpanzee genome. Our results provide detailed information on recent nucleotide changes and methylation-dependent transition rates in the chimpanzee genome after its split from the human. These results have important implications for understanding genome composition evolution, mechanisms of point mutation, and other genetic factors such as selection, biased codon usage, biased gene conversion, and recombination.
© 2006 Jiang and Zhao; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Frequencies of nucleotide changes in intergenic regions. Supplementary Table S1 – Frequencies (%) of nucleotide changes in intergenic regions.
1471-2164-7-316-s2.pdf (15 kB)
Linear regression of the frequency of nucleotide changes versus GC content in intergenic regions. Supplementary Figure S1 – Linear regression of the frequency of each type of nucleotide changes versus GC content in intergenic regions.
1471-2164-7-316-s3.pdf (16 kB)
Frequency difference of nucleotide changes between chimpanzees and humans in each genomic category. Supplementary Figure S2 – Frequency difference of nucleotide changes between chimpanzees and humans in each genomic category.
1471-2164-7-316-s4.pdf (20 kB)
Frequency difference of nucleotide changes for each pair of syntenic chimpanzee and human chromosomes. Supplementary Figure S3 – Frequency difference of nucleotide changes for each pair of syntenic chimpanzee and human chromosomes.