Transcription-associated mutational asymmetry in mammalian evolution

Nat Genet. 2003 Apr;33(4):514-7. doi: 10.1038/ng1103. Epub 2003 Mar 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Evolution
  • Cell Lineage
  • Chromosomes, Human, Pair 22
  • CpG Islands
  • DNA Mutational Analysis*
  • Databases as Topic
  • Humans
  • Models, Genetic
  • Papio
  • RNA, Messenger / metabolism
  • Sequence Analysis, DNA
  • Transcription, Genetic*


  • RNA, Messenger