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