Spectrum of Mutations in the Human Genome Inferred by Single Nucleotide Polymorphisms

The spectrum of mutations in the human genome inferred by single nucleotide polymorphisms (SNPs) may be measured by three approaches: directly observed frequencies of nucleotide changes, relative frequencies of nucleotide changes by normalizing the nucleotide content and frequencies of nucleotide changes after excluding the CpG effect. The spectrum of mutations indicates that point mutation does not occur randomly in the human genome and varies between the categorized genomic regions.

Keywords: spectrum of mutations; mutation direction; single nucleotide polymorphisms (SNPs); nucleotide change; CpG effect

Figure 1. Inference of mutation direction by mapping human SNPs to chimpanzee genome sequences. HSPs: high-scoring segment pairs.
close
 References
    Cooper DN and Krawczak M (1990) The mutational spectrum of single base-pair substitutions causing human genetic disease: patterns and predictions. Human Genetics 85: 55–74.
    Fryxell KJ and Moon WJ (2005) CpG mutation rates in the human genome are highly dependent on local GC content. Molecular Biology and Evolution 22: 650–658.
    Galtier N, Piganeau G, Mouchiroud D et al. (2001) GC-content evolution in mammalian genomes: the biased gene conversion hypothesis. Genetics 159: 907–911.
    Gojobori T, Li WH and Graur D (1982) Patterns of nucleotide substitution in pseudogenes and functional genes. Journal of Molecular Evolution 18: 360–369.
    Green P, Ewing B, Miller W et al. (2003) Transcription-associated mutational asymmetry in mammalian evolution. Nature Genetics 33: 514–517.
    Hernandez RD, Williamson SH, Zhu L et al. (2007) Context-dependent mutation rates may cause spurious signatures of a fixation bias favoring higher GC-content in humans. Molecular Biology and Evolution 24: 2196–2202.
    Hess ST, Blake JD and Blake RD (1994) Wide variations in neighbor-dependent substitution rates. Journal of Molecular Biology 236: 1022–1033.
    Jiang C and Zhao Z (2006) Mutational spectrum in the recent human genome inferred by single nucleotide polymorphisms. Genomics 88: 527–534.
    Khelifi A, Meunier J, Duret L et al. (2006) GC content evolution of the human and mouse genomes: insights from the study of processed pseudogenes in regions of different recombination rates. Journal of Molecular Evolution 62: 745–752.
    Krawczak M, Ball EV and Cooper DN (1998) Neighboring-nucleotide effects on the rates of germ-line single-base-pair substitution in human genes. American Journal of Human Genetics 63: 474–488.
    Li WH, Wu CI and Luo CC (1984) Nonrandomness of point mutation as reflected in nucleotide substitutions in pseudogenes and its evolutionary implications. Journal of Molecular Evolution 21: 58–71.
    Malyarchuk BA, Rogozin IB, Berikov VB et al. (2002) Analysis of phylogenetically reconstructed mutational spectra in human mitochondrial DNA control region. Human Genetics 111: 46–53.
    Qu HQ, Lawrence SG, Guo F et al. (2006) Strand bias in complementary single-nucleotide polymorphisms of transcribed human sequences: evidence for functional effects of synonymous polymorphisms. BMC Genomics 7: 213.
    Siepel A and Haussler D (2004) Phylogenetic estimation of context-dependent substitution rates by maximum likelihood. Molecular Biology and Evolution 21: 468–488.
    Subramanian S and Kumar S (2003) Neutral substitutions occur at a faster rate in exons than in noncoding DNA in primate genomes. Genome Research 13: 838–844.
    Sved J and Bird A (1990) The expected equilibrium of the CpG dinucleotide in vertebrate genomes under a mutation model. Proceedings of the National Academy of Sciences of the USA 87: 4692–4696.
    Tang CS and Epstein RJ (2007) A structural split in the human genome. PLoS ONE 2: e603.
    Taylor J, Tyekucheva S, Zody M et al. (2006) Strong and weak male mutation bias at different sites in the primate genomes: insights from the human-chimpanzee comparison. Molecular Biology and Evolution 23: 565–573.
    Vitkup D, Sander C and Church GM (2003) The amino-acid mutational spectrum of human genetic disease. Genome Biology 4: R72.
    Wang GZ, Chen LL and Zhang HY (2007) Phase-dependent nucleotide substitution in protein-coding sequences. Biochemical and Biophysical Research Communications 355: 599–602.
    Watanabe H, Fujiyama A, Hattori M et al. (2004) DNA sequence and comparative analysis of chimpanzee chromosome 22. Nature 429: 382–388.
    Webster MT, Smith NGC and Ellegren H (2003) Compositional evolution of noncoding DNA in the human and chimpanzee genomes. Molecular Biology and Evolution 20: 278–286.
    Zhang W, Bouffard GG, Wallace SS et al. (2007) Estimation of DNA sequence context-dependent mutation rates using primate genomic sequences. Journal of Molecular Evolution 65: 207–214.
    Zhao Z and Boerwinkle E (2002) Neighboring-nucleotide effects on single nucleotide polymorphisms: a study of 2.6 million polymorphisms across the human genome. Genome Research 12: 1679–1686.
    Zhao Z and Jiang C (2007) Methylation-dependent transition rates are dependent on local sequence lengths and genomic regions. Molecular Biology and Evolution 24: 23–25.
    Zhao Z, Jin L, Fu YX et al. (2000) Worldwide DNA sequence variation in a 10-kilobase noncoding region on human chromosome 22. Proceedings of the National Academy of Sciences of the USA 97: 11354–11358.
    Zhao Z and Zhang F (2006) Sequence context analysis of 8.2 million single nucleotide polymorphisms in the human genome. Gene 366: 316–324.
 Further Reading
    Bird AP (1980) DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Research 8: 1499–1504.
    Blake RD, Hess ST and Nicholson-Tuell J (1992) The influence of nearest neighbors on the rate and pattern of spontaneous point mutations. Journal of Molecular Evolution 34: 189–200.
    book Li WH (1997) Molecular Evolution. Sunderland, MA: Sinauer Associates.
 Web Links
    ePath CpG island searcher program (CpGi130) http://cpgislands.usc.edu/
    ePath Ensembl database ftp://ftp.ensembl.org/pub/
    ePath MegaBLAST program http://www.ncbi.nlm.nih.gov/blast/download.shtml
    ePath NCBI dbSNP database http://www.ncbi.nlm.nih.gov/SNP/
    ePath NCBI reference sequences ftp://ftp.ncbi.nih.gov/genomes/
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Zhongming, Zhao(Mar 2008) Spectrum of Mutations in the Human Genome Inferred by Single Nucleotide Polymorphisms. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020852]