Fig. 1: Experimental study design and data overview.

a Left: C. elegans wild-type (WT) and mutants of selected genes from the indicated DNA repair pathways were propagated over several generations or exposed to increasing doses of 12 different genotoxins. Genomic DNA from samples before and after propagation or without and with treatment was sequenced to determine mutational spectra (Methods). Right: representative experimental mutational spectra across 119 mutation classes: 96 single base substitutions classified by the 6 possible base changes in their ‘5 and 3’ base context, di- and multi-nucleotide variants (MNV), 6 classes of deletions of different length and context, 2 classes of complex indels, 6 classes of insertions and 7 classes of structural variants (see panel d for the list of mutation classes). Individual bars represent the average number of mutations observed per mutation class. b 2D t-SNE representation of all C. elegans samples based on the cosine similarity between mutational profiles. Dots represent individual sequenced samples, with dot sizes proportional to the number of observed mutations. Colours depict genotoxin exposures, mutation accumulation samples are not couloured. Black boxes highlight selected genotoxins and DNA repair deficiencies. c Experimental mutational signatures of selected DNA repair deficiencies. Each bar corresponds to the estimated mean number of mutations of a particular mutation class per propagated generation. Error bars denote 95% credible intervals. See panel d for the list of mutation classes. d Experimental mutational signatures of selected genotoxin exposures in wild-type C. elegans. Each bar corresponds to the estimated mean number of mutations of a particular mutation class per generation per dose. Error bars denote 95% credible intervals.