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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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Compensatory mutations potentiate constructive neutral evolution by gene duplication.

Philippe C Després1,2,3,4, Alexandre K Dubé1,2,3,4,5, Marie-Ève Picard1,2,3

  • 1Département de Biochimie, de Microbiologie et de Bio-informatique, Faculté des Sciences et de Génie Université Laval, Québec, QC G1V 0A6, Canada.

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Gene duplication can lead to new protein functions without positive selection. Deleterious mutations in duplicated genes can be compensated, forming functional protein complexes through constructive neutral evolution.

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Area of Science:

  • Evolutionary biology
  • Molecular biology
  • Protein biochemistry

Background:

  • Protein function relies on complex assembly.
  • Evolutionary transitions from homomers to heteromers occur via gene duplication.
  • Intermolecular compensatory mutations can drive these transitions without adaptive evolution.

Purpose of the Study:

  • To experimentally investigate the evolution of heteromeric complexes from homodimeric enzymes.
  • To determine if gene duplication followed by deleterious mutations can lead to new functional complexes.
  • To understand the mechanisms underlying constructive neutral evolution.

Main Methods:

  • Experimental gene duplication and evolution of a homodimeric enzyme.
  • Analysis of mutations affecting homodimer and heteromer function.
  • Structural determination of a novel heteromeric complex.

Main Results:

  • Hundreds of deleterious mutations were identified that inactivate individual homodimers.
  • These mutations resulted in functional enzymes upon coexpression and heterodimerization of duplicated proteins.
  • Structural analysis revealed asymmetry buffering loss-of-function mutations, enabling subfunctionalization.

Conclusions:

  • Gene duplication followed by deleterious mutations can lead to the formation of functional heteromeric complexes.
  • Constructive neutral evolution can occur without adaptive evolution, driven by compensatory mutations.
  • Protein complex evolution can proceed through subfunctionalization facilitated by structural asymmetry.