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Scopel, E. F.

Publications and source records attributed to Scopel, E. F..

3 recordsLinked to original sources

Footprints of human migration in the population structure of wild wine yeast

Humans have a long history of fermenting food and beverages that led to domestication of the wine yeast, Saccharomyces cerevisiae. Despite their tight companionship with humans, yeast species that are domesticated or pathogenic can also live on trees. Here we used over 300 genomes of S. cerevisiae from oaks and other trees to determine whether tree-associated populations are genetically distinct from domesticated lineages and estimate the timing of forest lineage divergence. We found populations on trees are highly structured within Europe, Japan, and North America. Approximate estimates of when forest lineages diverged out of Asia and into North America and Europe coincide with the end of the last ice age, the spread of agriculture, and the onset of fermentation by humans. It appears that migration from human-associated environments to trees is ongoing. Indeed, patterns of ancestry in the genomes of three recent migrants from the trees of North America to Europe could be explained by the human response to the Great French Wine Blight. Our results suggest that human-assisted migration affects forest populations, albeit rarely. Such migration events may even have shaped the global distribution of S. cerevisiae. Given the potential for lasting impacts due to yeast migration between human and natural environments, it seems important to understand the evolution of human commensals and pathogens in wild niches.

evolutionary biology↗

Antifungal tolerance and resistance emerge at distinct drug concentrations and rely upon different aneuploid chromosomes

Antifungal drug tolerance is a response distinct from resistance, in which cells grow slowly above the minimum inhibitory drug concentration (MIC). Here we found that the majority (69.2%) of 133 Candida albicans clinical isolates, including standard lab strain SC5314, exhibited temperature-enhanced tolerance at 37{degrees}C and 39{degrees}C, and were not tolerant at 30{degrees}C. Other isolates were either always tolerant (23.3%) or never tolerant (7.5%) at these three temperatures, suggesting that tolerance requires different physiological processes in different isolates. At supra-MIC fluconazole concentrations (8-128 g/ml), tolerant colonies emerged rapidly at a frequency of ~10-3. In liquid passages over a broader range of fluconazole concentrations (0.25-128 g/ml), tolerance emerged rapidly (within one passage) at supra-MIC concentrations. By contrast, resistance appeared at sub-MIC concentrations after 5 or more passages. Of 155 adaptors that evolved higher tolerance, all carried one of several recurrent aneuploid chromosomes, often including chromosome R, alone or in combination with other chromosomes. Furthermore, loss of these recurrent aneuploidies was associated with a loss of acquired tolerance, indicating that specific aneuploidies confer fluconazole tolerance. Thus, genetic background and physiology, and the degree of drug stress (above or below the MIC) influence the evolutionary trajectories and dynamics with which antifungal drug resistance or tolerance emerges. ImportanceAntifungal drug tolerance differs from drug resistance: tolerant cells grow slowly in drug, while resistant cells usually grow well, due to mutations in a few known genes. More than half of Candida albicans clinical isolates have higher tolerance at body temperature than they do at the lower temperatures used for most lab experiments. This implies that different isolates achieve drug tolerance via several cellular processes. When we evolved different strains at a range of high drug concentrations above inhibitory levels, tolerance emerged rapidly and at high frequency (one in 1000 cells) while resistance only appeared later at very low drug concentrations. An extra copy of all or part of chromosome R was associated with tolerance, while point mutations or different aneuploidies were seen with resistance. Thus, genetic background and physiology, temperature, and drug concentration all influence how drug tolerance or resistance evolves.

evolutionary biology↗

Genetic variation in aneuploidy prevalence and tolerance across the Saccharomyces cerevisiae phylogeny

Individuals carrying an aberrant number of chromosomes can vary widely in their expression of aneuploidy phenotypes. A major unanswered question is the degree to which an individuals genetic makeup influences its tolerance of karyotypic imbalance. Here we took a population genetics perspective to investigate the selective forces influencing aneuploidy prevalence in Saccharomyces cerevisiae populations as a model for eukaryotic biology. We analyzed genotypic and phenotypic variation recently published for over 1,000 S. cerevisiae strains spanning dozens of genetically defined clades and ecological associations. Our results show that the prevalence of chromosome gain and loss varies by clade and can be better explained by differences in genetic background than ecology. The phylogenetic context of lineages showing high aneuploidy rates suggests that increased aneuploidy frequency arose multiple times in S. cerevisiae evolution. Separate from aneuploidy frequency, analyzing growth phenotypes reveals that some backgrounds - such as European Wine strains - show fitness costs upon chromosome duplication, whereas other clades with high aneuploidy rates show little evidence of major deleterious effects. Our analysis confirms that chromosome amplification can produce phenotypic benefits that can influence evolutionary trajectories. These results have important implications for understanding genetic variation in aneuploidy prevalence in health, disease, and evolution. ARTICLE SUMMARYAneuploidy, an imbalance in the normal chromosome copy number, is detrimental during human development; yet individuals show substantial variability in their aneuploidy susceptibility, suggesting the influence of genetic background on aneuploidy tolerance. Scopel et al. employed a population genetic approach to address this question, analyzing over 1,000 published Saccharomyces cerevisiae genomes. The results demonstrate that genetic background has a substantial effect on aneuploidy frequency and cellular tolerance of aneuploidy stress, presenting important new information on the forces that contribute to aneuploidy prevalence.

genetics↗