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Related Concept Videos

Gene Evolution - Fast or Slow?02:05

Gene Evolution - Fast or Slow?

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The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
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The theory of catalytically perfect enzymes was first proposed by W.J. Albery and J. R. Knowles in 1976. These enzymes catalyze biochemical reactions at high-speed. Their catalytic efficiency values range from 108-109 M-1s-1. These enzymes are also called 'diffusion-controlled' as the only rate-limiting step in the catalysis is that of the substrate diffusion into the active site. Examples include triose phosphate isomerase, fumarase, and superoxide dismutase.
 
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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
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Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
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To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
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Related Experiment Video

Updated: Jun 13, 2025

Directed Evolution Method in Saccharomyces cerevisiae: Mutant Library Creation and Screening
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Directed Evolution Method in Saccharomyces cerevisiae: Mutant Library Creation and Screening

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Enriching productive mutational paths accelerates enzyme evolution.

David Patsch1,2, Thomas Schwander1, Moritz Voss1

  • 1Competence Center for Biocatalysis, Zurich University of Applied Sciences, Waedenswil, Switzerland.

Nature Chemical Biology
|September 11, 2024
PubMed
Summary
This summary is machine-generated.

Scientists accelerated enzyme evolution using computational design and gene synthesis. This rapid method created a novel Kemp eliminase with over 10^8-fold catalytic enhancement in just five rounds.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Enzyme Engineering

Background:

  • Darwinian evolution produced Earth's enzymes.
  • Enzyme engineering mimics natural selection via mutation, selection, and amplification.
  • Screening large protein libraries is common but complex.

Purpose of the Study:

  • To accelerate the evolution of computationally designed enzymes.
  • To generate a Kemp eliminase, a model for proton transfer from carbon.
  • To explore enzyme fitness landscapes.

Main Methods:

  • Removing destabilizing mutations during library design.
  • Utilizing advances in gene synthesis.
  • Employing recursive cycles of mutation, selection, and amplification.

Main Results:

  • Generated a Kemp eliminase in only five rounds of evolution.
  • Achieved >10^8-fold acceleration of the proton abstraction step.
  • Mapped the fitness landscape of the designer enzyme.

Conclusions:

  • Enzyme evolution can be significantly accelerated.
  • Computational design combined with gene synthesis is effective.
  • Protein scaffolds can support multiple solutions for catalysis.