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Related Experiment Videos

Pathogen-driven selection and worldwide HLA class I diversity.

Franck Prugnolle1, Andrea Manica, Marie Charpentier

  • 1Theoretical and Molecular Population Genetics Group, Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, United Kingdom. prugnolle@yahoo.fr

Current Biology : CB
|June 7, 2005
PubMed
Summary

Human leukocyte antigen (HLA) diversity is influenced by colonization history and pathogen richness. Populations in areas with more pathogens show greater HLA diversity, supporting the pathogen-driven balancing selection hypothesis, especially for HLA B genes.

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Area of Science:

  • Immunogenetics
  • Human Evolution
  • Population Genetics

Background:

  • The human leukocyte antigen (HLA) complex is the most polymorphic region in the human genome.
  • The remarkable polymorphism is hypothesized to be driven by pathogen-driven balancing selection (PDBS).
  • Direct evidence supporting PDBS as the primary driver of HLA polymorphism is lacking.

Purpose of the Study:

  • To test the prediction that higher local pathogen diversity correlates with increased HLA diversity.
  • To investigate the role of human colonization history and pathogen richness in shaping HLA genetic diversity.
  • To compare the influence of pathogen richness on different HLA class I genes (A, B, and C).

Main Methods:

  • Analysis of HLA class I genetic diversity data from 61 human populations.

Related Experiment Videos

  • Statistical correlation between HLA diversity, human colonization history, and local pathogen richness.
  • Comparative analysis of variation explained by pathogen richness across HLA A, B, and C genes.

    • Main Results:

    • Human colonization history significantly explains global HLA genetic diversity.
    • A positive correlation exists between HLA class I gene diversity and local pathogen richness.
    • The HLA B gene shows a stronger positive correlation with pathogen richness than HLA A and C genes.

    Conclusions:

    • Both human colonization history and pathogen richness contribute to global HLA diversity.
    • Findings provide direct support for the pathogen-driven balancing selection (PDBS) hypothesis.
    • The HLA B gene appears to be under stronger selective pressure from pathogens compared to HLA A and C.