ArticleCell2018
Scalable, Continuous Evolution of Genes at Mutation Rates above Genomic Error Thresholds.
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
166 citing papers in PubMed.
- Hijacking host RNA polymerase for processive in situ mutagenesis.Synthetic and systems biotechnology · 2027Article
- Article
- Engineered bacteria in disease diagnosis and therapy: A synthetic biology perspective.Synthetic and systems biotechnology · 2026Review
- Predicting resistance evolution to guide antibiotic development.Nature reviews. Microbiology · 2026Review
- Harnessing the central dogma: Enzyme-driven gene diversification strategies for in cellulo continuous directed evolution.Fundamental research · 2026Review
- Exploring the Evolutionary Landscape with Targeted In Vivo Hypermutations.Biomedicines · 2026Review
- The power of many: when genetics met yeasts and high-throughput.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Single-residue engineering of Klenow fragment enables broad acceptance of chemically modified nucleotides.Nucleic acids research · 2026Article
- Stress-Driven Accelerated Evolution and Ecological Network Reconfiguration in Extremophilic Microbial Communities.Biology · 2026Review
- Extrachromosomally co-encoded toxin-immunity pairs in yeast and their application potential.Applied microbiology and biotechnology · 2026Review
- Directed evolution of enzymes at the crossroads of tradition and innovation.FEBS open bio · 2026Review
- Harnessing Nature's Algorithm: From Test Tubes to Autonomous In Vivo Evolution.Biotechnology journal · 2026Review
- Diversity-generating retroelements for programmable targeted hypermutagenesis.Nature biotechnology · 2026Article
- Continuous Directed Evolution of a Short-Lived Plant Histidinol Dehydrogenase.ACS synthetic biology · 2026Article
- High-throughput methods enabling random duplications, deletions, or nucleotide-constrained mutagenesis of entire DNA motifs.Nucleic acids research · 2026Article
- From Gene Knockouts to Genome Remodeling: Large DNA Fragment Deletion Technologies in Plants.Plants (Basel, Switzerland) · 2026Review
- MicroDFBEST: A dCas12b-derived dual-function base editor with programmable editing characteristics for microbial genetic engineering.Synthetic and systems biotechnology · 2026Article
- Highly mutagenic continuous evolution in E. coli using a Φ29-based orthogonal replication system.Nature biotechnology · 2026Article
- Synthetic Biology of Plants and Microbes for Agriculture, Environment, and Future Applications.Chemical reviews · 2026Review
- Continuous Hypermutation and Evolution of Luciferase Variants.ACS chemical biology · 2026Article
106 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
Directed evolution is a powerful approach for engineering biomolecules and understanding adaptation. However, experimental strategies for directed evolution are notoriously labor intensive and low throughput, limiting access to demanding functions, multiple functions in parallel, and the study of molecular evolution in replicate. We report OrthoRep, an orthogonal DNA polymerase-plasmid pair in yeast that stably mutates ∼100,000-fold faster than the host genome in vivo, exceeding the error threshold of genomic replication that causes single-generation extinction. User-defined genes in OrthoRep continuously and rapidly evolve through serial passaging, a highly straightforward and scalable process. Using OrthoRep, we evolved drug-resistant malarial dihydrofolate reductases (DHFRs) in 90 independent replicates. We uncovered a more complex fitness landscape than previously realized, including common adaptive trajectories constrained by epistasis, rare outcomes that avoid a frequent early adaptive mutation, and a suboptimal fitness peak that occasionally traps evolving populations. OrthoRep enables a new paradigm of routine, high-throughput evolution of biomolecular and cellular function.
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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.