1Mutations in genomic DNA are the starting material for evolution by natural 2 selection. Analyses of large-scale sequencing data have revealed that mu-3 tagenic processes often create distinctive patterns of base substitutions, 4 called mutational signatures. In this work, we analyzed the base substitu-5 tion patterns within mutational data from a large number of strains or indi-6 viduals among seven model species (totalling >784 million mutations), as 7 well as single nucleotide polymorphisms (SNPs) in 41 species from the 8 NCBI SNP database (>603 million SNPs). We found that the intrinsic base 9 substitution pattern for most of these species closely matches mutational 10 signature 5 from the Catalog of Somatic Mutations in Cancer (abbreviated 11 as COSMIC). Signature 5 is ubiquitous in cancers and normal human cells, 12suggesting that the similar patterns of mutation across many species are 13 likely due to conserved biochemical processes. Finally, we show that a 14 similar pattern of base substitutions can be obtained using a yeast model 15 system that allows controlled generation of genomic single-stranded DNA. 16Taken together, we propose that intrinsic biochemical processes in cells 17 are coupled to the continuous generation of mutations, which in turn, are 18 acted upon by natural selection to drive the evolution of species. 19 20