title: Distinct contributions of replication and transcription to mutation rate variation of human genomes.
abstract: Here, we evaluate the contribution of two major biological processes--DNA replication and transcription--to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cui
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lin
authors.forename: Lingfang
authors.initials: L
authors.lastname: Zhang
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Songnian
authors.initials: S
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D004261:DNA Replication; D020043:Genes, Essential; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D059645:Mutation Rate; D009928:Organ Specificity; D020641:Polymorphism, Single Nucleotide; D014158:Transcription, Genetic; D059467:Transcriptome