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, ...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 expres- sion breadth, replication time in local regions and SNP density. SNP density of tissue-specific （TS） genes is sig- nificantly higher than that of housekeeping （HK） genes. TS genes tend to locate in late-replicating genomic re- gions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addi- tion, 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.展开更多
基金supported by grants from the National Basic Research Program (973 Program 2006CB9-10401 and 2006CB910403) awarded to JY and SH
文摘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 expres- sion breadth, replication time in local regions and SNP density. SNP density of tissue-specific （TS） genes is sig- nificantly higher than that of housekeeping （HK） genes. TS genes tend to locate in late-replicating genomic re- gions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addi- tion, 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.
