Region-specific rates of molecular evolution: A fourfold reduction in the rate of accumulation of “Silent” mutations in transcribed versus nontranscribed regions of homologous DNA fragments derived from two closely related mouse species

Mitchell S. Turker, Gregory E. Cooper, Peggy L. Bishop

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

We have sequenced homologous DNA fragments of 2.7 and 2.8 kbp derived from the closely related mouse species Mus musculus domesticus (M. domesticus) and Mus musculus musculus (M. musculus), respectively. These two species diverged approximately 1 million years ago. Each DNA fragment contains 1.35 kbp of the 3′ end of the constitutively expressed 2.2-kbp aprt (adenine phosphoribosyltransferase) gene and a similarly sized nontranscribed region downstream of the aprt gene. The aprt gene region contains protein coding sequences (0.35 kbp), intronic sequences (0.75 kbp), and a 3′ nontranslated sequence (0.25 kbp). Both the M. domesticus and M. musculus downstream regions share three partial copies of the B1 repetitive element with the M. musculus downstream region containing an additional complete copy of this element. A comparison of the 2.7-and 2.8-kbp DNA fragments revealed a total of 63 molecular alterations (i.e., mutations) that were approximately fourfold more abundant in the nontranscribed downstream region than in the transcribed aprt gene. Of the 11 mutations observed in the transcribed region, 7 were found in introns, 3 in the 3′ untranslated sequence, and 1 was a synonymous change in an exon. A comparison of the human and M. domesticus aprt genes has previously revealed no homology in either the intronic or 3′ nontranslated regions with the exception of a 26-bp sequence in intron 3 and sequences at the exon/intron boundaries necessary for correct mRNA splicing (Broderick et al., Proc. Natl. Acad. Sci. USA, 84:3349, 1987). Therefore, there does not appear to be selective pressure for sequences within these regions. We conclude that there is a lower rate of accumulation of “silent” mutations in the transcribed mouse aprt gene than in a contiguous nontranscribed downstream region. A possible molecular mechanism involving preferential DNA repair for the transcribed region is discussed.

Original languageEnglish (US)
Pages (from-to)31-40
Number of pages10
JournalJournal of Molecular Evolution
Volume36
Issue number1
DOIs
StatePublished - Jan 1993

Keywords

  • B1 sequences
  • Intergenic region
  • Mouse
  • Silent mutations
  • Transcription unit

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics

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