| Summary: | 博士 === 國防醫學院 === 生命科學研究所 === 99 === Various types of genetic modification 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. A set of yeast strains collected from Evolution Canyon (EC), Israel, were observed to exhibit extremely high tolerance to two heavy metals, copper and cadmium. We found that large-scale chromosomal rearrangements creating multiple copies of genes involved in copper regulation contribute mainly to copper resistance. On the other hand, cadmium resistance is primarily caused by small-scale sequence changes in a metal efflux pump, PCA1. Molecular analyses demonstrate that the enhanced PCA1 function can be largely attributed to mutations in the promoter sequence, while mutations in the coding region have a minor effect. Reconstitution experiments show that three single nucleotide substitutions in the PCA1 promoter quantitatively increase its activity, suggesting that PCA1 has experienced continuous directional selection. Comparison between different yeast species shows that these critical nucleotides had diverged in S. cerevisiae, which gave cells growth advantages under non-cadmium conditions. This fitness trade-off may explain the loss of function of cadmium resistance in most S. cerevisiae populations. Our results suggest that by large scale genome reorganization and small scale regulatory changes, natural populations can adapt to diverse environments . Moreover, our results also suggest regulatory changes are critical for adaptive evolution.
|
|---|
