Unknown,Transcriptomics,Genomics,Proteomics

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Tracking the dynamics and diversity of segmental amplification in evolving populations of Saccharomyces cerevisiae

ABSTRACT: Population adaptation to strong selection can occur through the sequential or parallel accumulation of competing beneficial mutations. The dynamics, diversity and rate of fixation of beneficial mutations within and between populations are still poorly understood. To study the changes in the mutational landscape across populations during adaptation, we performed experimental evolutions on seven parallel populations of Saccharomyces cerevisiae continuously cultured in limiting sulfate medium. By combining qPCR, array CGH, restriction, digestion and CHEF gels, and whole genome sequencing, we followed the trajectory of evolution to determine the identity and fate of beneficial mutations. Over a period of 200 generations, the yeast populations displayed parallel evolutionary dynamics that are driven by the coexistence of independent beneficial mutations. Segmental amplifications are rapidly gained under this selective pressure, including, common inverted amplifications containing the sulfate transporter gene SUL1. Detailed analysis of the populations uncovers a deep complexity where by multiple subpopulations arise and compete with each another. The most common trajectories to adaptation in these populations are incomplete soft sweeps, with adaptive variants replacing one another. These are CGH arrays. Each experiment compares the DNA content of an experimentally evolved strain with its ancestor.

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Maitreya Dunham

PROVIDER: E-GEOD-47854 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Aneuploidy is a hallmark of tumor cells and yet the precise relationship between aneuploidy and a cell’s proliferative ability, or cellular fitness, has remained elusive. In this study we have combined a detailed analysis of aneuploid clones isolated from laboratory-evolved populations of Saccharomyces cerevisiae with a systematic, genome-wide screen for the fitness effects of telomeric amplifications to address the relationship between aneuploidy and cellular fitness. We found that aneuploid clones rise to high population frequencies in nutrient-limited evolution experiments and show increased fitness relative to wild-type. Direct competition experiments confirmed that three out of four aneuploid events isolated from evolved populations were themselves sufficient to improve fitness. To expand the scope beyond this small number of exemplars, we created a genome-wide collection of >1,800 diploid yeast strains each containing a different telomeric amplicon (Tamp) ranging in size from 0.4 to 1,000kb. Using pooled competition experiments in nutrient-limited chemostats followed by high-throughput sequencing of strain-identifying barcodes, we determined the fitness effects of these >1,800 Tamps under three different conditions. Our data revealed that the fitness landscape explored by telomeric amplifications is much broader than that explored by single-gene amplifications. As also observed in the evolved clones, we found the fitness effects of most Tamps to be condition specific with a minority showing common effects in all three conditions. By integrating our data with previous work that examined the fitness effects of single-gene amplifications genome wide, we found that a small number of genes within each Tamp are centrally responsible for each Tamp’s fitness effects. Our genome-wide Tamp screen confirmed that telomeric amplifications identified in laboratory-evolved populations generally increased fitness. Our results show that Tamps are mutations that produce large, typically condition-dependent changes in fitness that are important drivers of increased fitness in asexually evolving populations. Each of these arrays is a Comparative Genomic Hybridization experiment to detect copy number differences between a reference strain and a strain of interest.

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Tracking the dynamics and diversity of segmental amplification in evolving populations of Saccharomyces cerevisiae

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