Evidence map›Paper›PMID 39509492›Full record

ArticleScience (New York, N.Y.)2024

Continuous evolution of user-defined genes at 1 million times the genomic mutation rate.

Gordon Rix, Rory L Williams, Vincent J Hu, Aviv Spinner, Alexander Olek Pisera, Debora S Marks, Chang C Liu

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed.

  1. Article
  2. Phage-assisted continuous evolution of enzymes for noncanonical tyrosine biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. OpenEvo: An Open-Source Platform for Automated Evolution and Analysis.bioRxiv : the preprint server for biology · 2026
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Gordon RixDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92617, USA.ORCID 0000-0001-7217-8535
Rory L WilliamsDepartment of Biomedical Engineering, University of California, Irvine, CA 92617, USA.ORCID 0000-0003-2605-5790
Vincent J HuDepartment of Biomedical Engineering, University of California, Irvine, CA 92617, USA.ORCID 0000-0001-8580-067X
Aviv SpinnerDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-9845-0787
Alexander Olek PiseraDepartment of Biomedical Engineering, University of California, Irvine, CA 92617, USA.
Debora S MarksDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Chang C LiuDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92617, USA.ORCID 0000-0002-3290-2880

Funding

Making antibody generation rapid, scalable, and democratic through machine learning and continuous evolutionR01CA260415 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI KRUSE, ANDREW, LIU, CHANG C · 2020 to 2024
$8.4M
Synthetic genetic systems for rapid biomolecular evolution in vivoR35GM136297 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI LIU, CHANG C · 2020 to 2024
$2.4M
NCI NIH HHS R01 CA260415NIGMS NIH HHS R35 GM136297
6 · The paper itself

Abstract

When nature evolves a gene over eons at scale, it produces a diversity of homologous sequences with patterns of conservation and change that contain rich structural, functional, and historical information about the gene. However, natural gene diversity accumulates slowly and likely excludes large regions of functional sequence space, limiting the information that is encoded and extractable. We introduce upgraded orthogonal DNA replication (OrthoRep) systems that radically accelerate the evolution of chosen genes under selection in yeast. When applied to a maladapted biosynthetic enzyme, we obtained collections of extensively diverged sequences with patterns that revealed structural and environmental constraints shaping the enzyme's activity. Our upgraded OrthoRep systems should support the discovery of factors influencing gene evolution, uncover previously unknown regions of fitness landscapes, and find broad applications in biomolecular engineering.

Indexed as

DNA ReplicationEvolution, MolecularMutation RateGenome, FungalMutagenesisSaccharomyces cerevisiaeSelection, Genetic

Identifiers

PMID39509492
PMCPMC11750425

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.