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Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...
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In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...
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Microbial membranes exhibit remarkable diversity in lipid composition, reflecting evolutionary adaptations to various environmental conditions. The three domains of life—Bacteria, Archaea, and Eukarya—synthesize membrane lipids through distinct biosynthetic pathways, leading to fundamental structural differences that impact membrane stability, function, and adaptability.Fatty Acid-Based Lipids in Bacteria and EukaryaBacteria and eukaryotes share a common fatty acid biosynthesis...
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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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Sparse Epistatic Patterns in the Evolution of Terpene Synthases.

Aditya Ballal1, Caroline Laurendon2,3, Melissa Salmon2,3,4

  • 1Department of Physics & Astronomy and Center for Quantitative Biology, Rutgers University, Piscataway, NJ.

Molecular Biology and Evolution
|March 3, 2020
PubMed
Summary

Researchers studied enzyme evolution by analyzing mutations in terpene synthases. They found that enzyme activity and specificity are determined by sequence, with simple landscapes governing evolutionary changes.

Keywords:
enzyme kineticsepistasismolecular evolutionterpene synthases

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Area of Science:

  • Biochemistry and Molecular Biology
  • Enzyme kinetics and evolution
  • Natural product biosynthesis

Background:

  • Terpene synthases are crucial enzymes producing diverse cyclic hydrocarbons used in biological processes.
  • Understanding enzyme evolution, particularly the emergence of cyclization, is key to deciphering complex biochemical pathways.
  • The (E)-β-farnesene synthase from Artemisia annua serves as a model for studying the transition from linear to cyclic terpene production.

Purpose of the Study:

  • To investigate the sequence determinants governing enzyme activity and specificity within the terpene synthase family.
  • To elucidate the molecular mechanisms underlying the evolution of terpene cyclization.
  • To develop and apply computational models for predicting enzyme kinetics and fitness landscapes.

Main Methods:

  • Systematic mutagenesis of (E)-β-farnesene synthase to create synthetic enzyme libraries.
  • Biochemical characterization of mutant enzymes to determine reaction rates.
  • Application of the Michaelis-Menten model with amino acid contributions and couplings to predict enzyme kinetics.
  • Development of biophysical fitness models to analyze evolutionary landscapes and epistasis.

Main Results:

  • The Michaelis-Menten model accurately predicted measured reaction rates, revealing simple, interpretable free energy landscapes with minimal epistasis.
  • Biophysical fitness models demonstrated that maximizing correct product output while minimizing byproducts leads to more complex, epistatic fitness landscapes.
  • The study successfully characterized the evolutionary emergence of novel enzymatic functions through microevolutionary exploration of sequence space.

Conclusions:

  • Enzyme activity and specificity are primarily dictated by sequence, with simple energetic landscapes facilitating evolutionary adaptation.
  • The interplay between enzyme function, fitness, and evolutionary constraints shapes the emergence of novel catalytic activities.
  • This framework provides a powerful approach for understanding enzyme evolution and engineering new biocatalysts.