title: Genomic evidence for elevated mutation rates in highly expressed genes.
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.
authors.affiliation: Department of Ecology and Evolutionary Biology, University of Michigan, 1075 Natural Science Building, 830 North University Avenue, Ann Arbor, Michigan 48109, USA.
authors.forename: Chungoo
authors.initials: C
authors.lastname: Park
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Qian
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Zhang
mesh_terms: D005786:Gene Expression Regulation; D016681:Genome, Fungal; D018095:Germ-Line Mutation; D006801:Humans; D016296:Mutagenesis; D059645:Mutation Rate; D017354:Point Mutation / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D014158:Transcription, Genetic