title: Transcription-associated mutational asymmetry in mammalian evolution.
abstract: Although 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 mechanisms. A strand asymmetry, the occurrence of particular substitution types at higher rates than their complementary types, that is associated with DNA replication has been found in bacteria and mitochondria. A strand asymmetry that is associated with transcription and attributable to higher rates of cytosine deamination on the coding strand has been observed in enterobacteria. Here, we describe a qualitatively different transcription-associated strand asymmetry in mammals, which may be a byproduct of transcription-coupled repair 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.
authors.affiliation: Howard Hughes Medical Institute and Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. phg@u.washington.edu
authors.forename: Phil
authors.initials: P
authors.lastname: Green
authors.forename: Brent
authors.initials: B
authors.lastname: Ewing
authors.forename: Webb
authors.initials: W
authors.lastname: Miller
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Thomas
authors.forename: Eric D
authors.initials: ED
authors.lastname: Green
mesh_terms: D000818:Animals; D005075:Biological Evolution; D019070:Cell Lineage; D002892:Chromosomes, Human, Pair 22; D018899:CpG Islands; D004252:DNA Mutational Analysis; D019992:Databases as Topic; D006801:Humans; D008957:Models, Genetic; D010215:Papio; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger