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.