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Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
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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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A Reverse Genetic Approach to Test Functional Redundancy During Embryogenesis
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Evolutionary regain of lost gene circuit function.

Mirna Kheir Gouda1,2, Michael Manhart3, Gábor Balázsi4,2

  • 1The Louis and Beatrice Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY 11794-5252.

Proceedings of the National Academy of Sciences of the United States of America
|November 23, 2019
PubMed
Summary
This summary is machine-generated.

Evolutionary reversibility allows yeast populations to regain lost gene circuit function. Mutations enabled adaptation and drug resistance, highlighting context-dependent evolutionary dynamics.

Keywords:
bistabilityevolutiongene circuitloss of functionreversal

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Area of Science:

  • Synthetic biology
  • Evolutionary biology
  • Genetics

Background:

  • Evolutionary reversibility, the capacity to regain lost functions, is crucial in both evolutionary and synthetic biology.
  • Synthetic gene circuits can be disrupted by evolutionary processes, necessitating methods for repair.
  • Positive-feedback (PF) gene circuits in yeast, previously rendered non-functional by mutations, serve as a model system.

Purpose of the Study:

  • To investigate if yeast populations can restore lost positive-feedback (PF) gene circuit function.
  • To identify adaptation mechanisms in response to drug selection pressure on compromised PF mutants.
  • To understand the role of intracellular context in evolutionary dynamics and gene circuit function.

Main Methods:

  • Utilized a synthetic positive-feedback (PF) gene circuit in haploid *Saccharomyces cerevisiae*.
  • Evolved seven PF mutant strains under selective pressure (drug and inducer).
  • Analyzed genomic and non-genomic adaptations to assess restoration of PF function and drug resistance.

Main Results:

  • Observed three distinct adaptation scenarios driven by genomic mutations affecting PF basal expression.
  • Nonfunctional mutants acquired drug resistance without restoring high PF expression.
  • Quasifunctional and dysfunctional mutants exhibited transient high expression, with slower functional recovery in dysfunctional strains.

Conclusions:

  • Intracellular context, including growth rate, significantly influences regulatory network and evolutionary dynamics.
  • Adaptation mechanisms vary based on the initial functional state of the gene circuit.
  • Findings have implications for understanding drug resistance evolution and advancing synthetic biology applications.