ArticleCell reports2017
Clonal Heterogeneity Influences the Fate of New Adaptive Mutations.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed.
- Exploring roles for essential proteins in yeast filamentous growth identifies the WASP homolog Las17 as a regulator of the Cdc42-dependent fMAPK pathway.bioRxiv : the preprint server for biology · 2026Article
- Estimating the distribution of fitness effects of loss of heterozygosity (LOH) events using an engineered library of Saccharomyces cerevisiae.PLoS genetics · 2026Article
- Predicting natural variation in the yeast phenotypic landscape with machine learning.Molecular systems biology · 2025Article
- Hybrid adaptation is hampered by Haldane's sieve.Nature communications · 2024Article
- Phenotyping of a new yeast mapping population reveals differences in the activation of the TORC1 signalling pathway between wild and domesticated yeast strains.Biological research · 2024Article
- Highly parallelized laboratory evolution of wine yeasts for enhanced metabolic phenotypes.Molecular systems biology · 2024Article
- Highly parallelized laboratory evolution of wine yeasts for enhanced metabolic phenotypes.Molecular systems biology · 2024Article
- Genome instability footprint under rapamycin and hydroxyurea treatments.PLoS genetics · 2023Article
- Quantitative systems-based prediction of antimicrobial resistance evolution.NPJ systems biology and applications · 2023Review
- Long-term evolution of proliferating cells using the eVOLVER platform.Open biology · 2023Article
- Embracing Complexity: Yeast Evolution Experiments Featuring Standing Genetic Variation.Journal of molecular evolution · 2023Review
- Loss of Heterozygosity and Its Importance in Evolution.Journal of molecular evolution · 2023Review
- Article
- Long-term evolution of proliferating cells using the eVOLVER platform.bioRxiv : the preprint server for biology · 2023Article
- Overexpression profiling reveals cellular requirements in the context of genetic backgrounds and environments.PLoS genetics · 2023Article
- Adaptation in Outbred Sexual Yeast is Repeatable, Polygenic and Favors Rare Haplotypes.Molecular biology and evolution · 2022Article
- Adaptation of the yeast gene knockout collection is near-perfectly predicted by fitness and diminishing return epistasis.G3 (Bethesda, Md.) · 2022Article
- The Dynamics of Adaptation to Stress from Standing Genetic Variation and de novo Mutations.Molecular biology and evolution · 2022Article
- Challenges and potential solutions for studying the genetic and phenotypic architecture of adaptation in microbes.Current opinion in genetics & development · 2022Review
- Rapid selection response to ethanol in Saccharomyces eubayanus emulates the domestication process under brewing conditions.Microbial biotechnology · 2022Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
The joint contribution of pre-existing and de novo genetic variation to clonal adaptation is poorly understood but essential to designing successful antimicrobial or cancer therapies. To address this, we evolve genetically diverse populations of budding yeast, S. cerevisiae, consisting of diploid cells with unique haplotype combinations. We study the asexual evolution of these populations under selective inhibition with chemotherapeutic drugs by time-resolved whole-genome sequencing and phenotyping. All populations undergo clonal expansions driven by de novo mutations but remain genetically and phenotypically diverse. The clones exhibit widespread genomic instability, rendering recessive de novo mutations homozygous and refining pre-existing variation. Finally, we decompose the fitness contributions of pre-existing and de novo mutations by creating a large recombinant library of adaptive mutations in an ensemble of genetic backgrounds. Both pre-existing and de novo mutations substantially contribute to fitness, and the relative fitness of pre-existing variants sets a selective threshold for new adaptive mutations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.