Various types of genetic modification and selective forces have been implicated
in the process of adaptation to novel or adverse environments. However, the
underlying molecular mechanisms are not well understood in most natural
populations. Here we report that a set of yeast strains collected from Evolution
Canyon (EC), Israel, exhibit an extremely high tolerance to the heavy metal
cadmium. We found that cadmium resistance is primarily caused by an enhanced
function of a metal efflux pump, PCA1. Molecular analyses
demonstrate that this enhancement can be largely attributed to mutations in the
promoter sequence, while mutations in the coding region have a minor effect.
Reconstruction experiments show that three single nucleotide substitutions in
the PCA1 promoter quantitatively increase its activity and thus
enhance the cells' cadmium resistance. Comparison among different yeast
species shows that the critical nucleotides found in EC strains are conserved
and functionally important for cadmium resistance in other species, suggesting
that they represent an ancestral type. However, these nucleotides had diverged
in most Saccharomyces cerevisiae populations, which gave cells
growth advantages under conditions where cadmium is low or absent. Our results
provide a rare example of a selective sweep in yeast populations driven by a
tradeoff in metal resistance