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Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis
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Polymorphic sites preferentially avoid co-evolving residues in MHC class I proteins.

Linda Dib1,2, Nicolas Salamin2,3, David Gfeller1,2

  • 1Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, Switzerland.

Plos Computational Biology
|May 22, 2018
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Summary

Polymorphic sites in Major Histocompatibility Complex class I (MHC-I) molecules avoid co-evolutionary constraints and protein stability residues. This suggests selection for increased mutability during vertebrate evolution.

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Area of Science:

  • Immunology
  • Evolutionary Biology
  • Structural Biology

Background:

  • Major histocompatibility complex class I (MHC-I) molecules are crucial for adaptive immunity in vertebrates.
  • MHC-I genes are highly polymorphic, influencing ligand-binding specificities.
  • Previous research explored polymorphism-stability links, but MHC-I co-evolutionary constraints remain understudied.

Purpose of the Study:

  • To investigate the relationship between polymorphism and co-evolutionary constraints in MHC-I molecules.
  • To determine if co-evolutionary signals in MHC-I are driven by inter-species changes or intra-species polymorphism.
  • To examine whether polymorphic sites in human MHC-I avoid co-evolving residues and those affecting protein stability.

Main Methods:

  • Direct Coupling Analysis (DCA) was employed to analyze co-evolutionary patterns.
  • The study focused on the MHC-I protein family within vertebrate species.

Main Results:

  • Co-evolution analysis successfully identified structural contacts in MHC-I.
  • The co-evolutionary signal in MHC-I is primarily driven by inter-species variations, not intra-species polymorphism.
  • Human MHC-I polymorphic sites tend to avoid residues involved in co-evolution and protein stability.

Conclusions:

  • High polymorphism in MHC-I may be an evolutionary strategy to circumvent co-evolutionary pressures.
  • Selection favors polymorphic sites that maximize mutability, enhancing adaptive potential.
  • These findings offer insights into the evolutionary dynamics of immune system genes.