Nature Genetics
33, 514 - 517 (2003)
Published online: 3 March 2003; | doi:10.1038/ng1103
Transcription-associated mutational asymmetry in mammalian evolutionPhil Green1, Brent Ewing1, Webb Miller2, Pamela J. Thomas3, NISC Comparative Sequencing Program 3, 4
& Eric D. Green3, 41
Howard Hughes Medical Institute and Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. 2
Department of Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA. 3
NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. 4
Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Correspondence should be addressed to Phil Green phg@u.washington.eduAlthough mutation is commonly thought of as a random process, evolutionary studies show that different types of nucleotide substitution occur with widely varying rates that presumably reflect biases intrinsic to mutation and repair mechanisms1,
2,
3,
4. A strand asymmetry5,
6, the occurrence of particular substitution types at higher rates than their complementary types, that is associated with DNA replication has been found in bacteria7 and mitochondria8. A strand asymmetry that is associated with transcription and attributable to higher rates of cytosine deamination on the coding strand has been observed in enterobacteria9,
10,
11. Here, we describe a qualitatively different transcription-associated strand asymmetry in mammals, which may be a byproduct of transcription-coupled repair12 in germline cells. This mutational asymmetry has acted over long periods of time to produce a compositional asymmetry, an excess of G+T over A+C on the coding strand, in most genes. The mutational and compositional asymmetries can be used to detect the orientations and approximate extents of transcribed regions.
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