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EMBO Rep. 2012 Dec;13(12):1123-9. doi: 10.1038/embor.2012.165. Epub 2012 Nov 13.

Genomic evidence for elevated mutation rates in highly expressed genes.

Author information

1
Department of Ecology and Evolutionary Biology, University of Michigan, 1075 Natural Science Building, 830 North University Avenue, Ann Arbor, Michigan 48109, USA.

Abstract

Reporter gene assays have demonstrated both transcription-associated mutagenesis (TAM) and transcription-coupled repair, but the net impact of transcription on mutation rate remains unclear, especially at the genomic scale. Using comparative genomics of related species as well as mutation accumulation lines, we show in yeast that the rate of point mutation in a gene increases with the expression level of the gene. Transcription induces mutagenesis on both DNA strands, indicating simultaneous actions of several TAM mechanisms. A significant positive correlation is also detected between the human germline mutation rate and expression level. These results indicate that transcription is overall mutagenic.

PMID:
23146897
PMCID:
PMC3512408
DOI:
10.1038/embor.2012.165
[Indexed for MEDLINE]
Free PMC Article

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