Figure 9

Multimetal toxicity signatures. Hierarchical clustering of cadmium and nickel tolerance-modulating mutations with the phenotypic profiles of other metals. Cadmium/nickel sensitive or resistant strains were exposed in triplicate to HgCl₂ (190 μmol/l), NaAsO₂ (1.5 mmol/l), CoCl₂ (2 mmol/l), ZnCl₂ (18 mmol/l), and FeCl₃ (15 mmol/l), followed by serial dilution assay verification of mutations affecting cell tolerance to this expanded set of metals (see 'Materials and methods' for details). The x-axis corresponds to the metals examined, and the y-axis indicates gene deletions. Mutants exhibiting either an enhanced sensitivity or resistance, or no phenotype are represented in green, red and black, respectively. Metal tolerance (from 'high sensitivity' [HS] to 'resistance' [R]) of the different mutant strains is indicated in a false color scale; only strains sensitive or resistant to at least two metals are shown (see Additional data file 7 for the entire database of multimetal phenotypes). Hierarchical clustering analysis was performed with EPCLUST, as specified in the legend to Figure 3, leaving out 67 cadmium-specific and nine nickel-specific gene mutations (listed in Additional data file 7). Representative genes and pathways affecting multimetal tolerance as well as a subset of co-clustering uncharacterized open reading frames with orthologous sequences in other organisms (see Additional data file 2) are indicated on the right-hand and left-hand, respectively.