Parallel Genetic Changes and Nonparallel Gene–Environment Interactions Characterize the Evolution of Drug Resistance in Yeast

Abstract

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.

Heterozygote Advantage Is a Common Outcome of Adaptation inSaccharomyces cerevisiae

“…If, however, it is also true in general, then there are important consequences on the dynamics of adaptation (Sellis et al 2011). We thus believe that a comprehensive comparison of adaptation in haploids and diploids is necessary and must involve multiple aspects of adaptation, such as the dynamics, rate of evolution, and size of mutation effects, and must also address the changes of ploidy in life cycles (Orr and Otto 1994;Gerstein and Otto 2009;Gerstein et al 2012;Szövényi et al 2013;Selmecki et al 2015). sporulate 4.2L…”

Evolutionary convergence in experimental Pseudomonas populations

“…The underlying causes have been the source of extensive study with understanding much accelerated in recent years through application of the tools of genomics and genetics (Jost et al, 2008;Gerstein et al, 2012;Tenaillon et al, 2012;Zhen et al, 2012;Barrick and Lenski, 2013;Herron and Doebeli, 2013). This has shifted focus from selection-often seen as the primary determinantto genetic details, in particular, the kinds of genes in which mutations are found and their regulatory connections (Gompel and Prud'homme, 2009;Stern, 2013).…”

“…This has shifted focus from selection-often seen as the primary determinantto genetic details, in particular, the kinds of genes in which mutations are found and their regulatory connections (Gompel and Prud'homme, 2009;Stern, 2013). Parallel evolution at both phenotypic and genetic levels has been extensively reported in laboratory populations of microbes (Wichman et al, 1999;McDonald et al, 2009;Gerstein et al, 2012;Barrick and Lenski, 2013;Herron and Doebeli, 2013;Lind et al, 2015). Given that replicate populations are typically founded by a single common ancestral type, that selection is often directional (and strong), and population sizes large, such parallelism is not surprising (Wichman et al, 1999).…”

Too Much of a Good Thing: The Unique and Repeated Paths Toward Copper Adaptation

“…We purposefully employed a short-term experimental design in an attempt to avoid the potential influence of epistasis limiting the mutations that are sampled (Chou et al 2011;Kvitek and Sherlock 2011). The design of the experiment was similar to a previous study in our group where we examined adaptation to the fungicide nystatin (Gerstein et al 2012). In both cases, multiple isogenic lines of yeast were exposed to inhibitory levels of either nystatin or copper, with levels chosen to be slightly higher than those in which growth occurred reliably.…”

“…We sequenced 100-bp single-end fragments for each line, pooling 12 uniquely barcoded strains in each lane on an Illumina HiSeq 2000. Twelve samples were rerun to obtain sufficient depth of coverage using 100-bp paired-end fragments: CBM18, 20, 21, 22, 24, 25, 26, 29, 30, 34, 36, and 44.The resulting genomic sequence data were processed using Illumina's CASAVA-1.8.0 as in Gerstein et al (2012). We called SNPs and small insertions and deletions using configure-Build.pl and parsed the output files with custom UNIX and perl scripts.…”