Mutagenic Characteristics of Six Heavy Metals in : The Commonality and Specificity

The history of long-term environmental exposure to heavy metals can be recorded in the genome as sporadic and specific mutations. Variable environments introduce diverse and adaptive mutations to organisms. To reveal the information hidden in genomes about environmental exposure to heavy metals, we performed long-term mutation accumulation (MA) experiments with , analyzed genomes from 36 populations across 1650 generations with 6 heavy metal exposure regimes (arsenic, cadmium, chromium, copper, nickel, and lead), and inferred metal-specific evolution modes at the genomic level. All heavy metals induced genetic mutations with a mean rate of 3.459 × 10 per nucleotide per generation. The mutational spectrum exhibited distinct signatures; however, heavy metals also shared common mutation signatures prominently associated with all cancer types. The mutated genes showed an average similarity of 54.4% within the same exposure regime, whereas only 38.8% between exposure regimes. In terms of biological insights, mutated genes were enriched to fundamental cellular processes such as metabolism, motility, and transport. Our study elucidates the mutagenic commonality and specificity of environmental heavy metals, which are highly specific at mutational features and locus, but conserved at gene and functional levels, and may play crucial roles in the convergence of adaptation to heavy metals.