Parallel Genetic Changes and Nonparallel Gene-Environment Interactions Characterize the Evolution of Drug Resistance in Yeast
Parallel Genetic Changes and Nonparallel Gene-Environment Interactions Characterize the Evolution of Drug Resistance in Yeast
复制标题
DOI：
10.1534/genetics.112.142620
复制
发表时间：
2012-09-01
期刊：
影响因子：
3.3
通讯作者：
Otto, Sarah P.
中科院分区：
文献类型：
--
作者：
Gerstein, Aleeza C.;Lo, Dara S.;Otto, Sarah P.
有益的突变是适应新环境所必需的，但对一个群体可用的突变途径的范围一直缺乏表征，特别是在真核生物中。我们评估了在适应新环境（暴露于杀真菌剂制霉菌素）的过程中获得的第一个突变的遗传变化，在35个单倍体酿酒酵母株系。通过全基因组重测序，我们发现，基因组范围的适应是狭窄的，所有适应线获得的突变在麦角固醇生物合成途径中的四个晚作用基因之一，与其他突变很少发现。发现所有品系在无压力环境中相对于野生型具有成本;该成本的水平也与具有突变的麦角固醇基因强烈相关。有趣的是，我们发现了不同麦角固醇基因突变对其他恶劣环境耐受性的积极和消极影响，表明这些有益的突变在环境挑战中具有不同的影响。这些结果表明，尽管基因组靶点很窄，但不同的适应性突变可以导致种群沿着不同的进化途径，就其耐受（或屈服于）其他环境挑战的能力而言。
Beneficial mutations are required for adaptation to novel environments, yet the range of mutational pathways that are available to a population has been poorly characterized, particularly in eukaryotes. We assessed the genetic changes of the first mutations acquired during adaptation to a novel environment (exposure to the fungicide, nystatin) in 35 haploid lines of Saccharomyces cerevisiae. Through whole-genome resequencing we found that the genomic scope for adaptation was narrow; all adapted lines acquired a mutation in one of four late-acting genes in the ergosterol biosynthesis pathway, with very few other mutations found. Lines that acquired different ergosterol mutations in the same gene exhibited very similar tolerance to nystatin. All lines were found to have a cost relative to wild type in an unstressful environment; the level of this cost was also strongly correlated with the ergosterol gene bearing the mutation. Interestingly, we uncovered both positive and negative effects on tolerance to other harsh environments for mutations in the different ergosterol genes, indicating that these beneficial mutations have effects that differ in sign among environmental challenges. These results demonstrate that although the genomic target was narrow, different adaptive mutations can lead populations down different evolutionary pathways, with respect to their ability to tolerate (or succumb to) other environmental challenges.