Evolution of major histocompatibility complex gene copy number.

Area of Science:

• Evolutionary biology
• Immunogenetics

Background:

• Major histocompatibility complex (MHC) genes exhibit significant copy-number variation across and within species.
• The evolutionary drivers of this MHC variation remain largely undetermined.

Purpose of the Study:

• To investigate the role of pathogen richness in shaping the evolution of MHC gene copy number using computer simulations.
• To explore how pathogen evolution rates and associated costs (e.g., autoimmunity) modify this relationship.

Main Methods:

• Computer simulations modeling host-pathogen interactions.
• Varying parameters for pathogen richness, pathogen evolution rates, and costs of expressing additional MHC variants.

Main Results:

• Pathogen richness drives increased MHC copy number only when the costs of expressing additional variants are low.
• Faster pathogen evolution rates select for higher host MHC copy number, but primarily at low to moderate pathogen richness.
• Within-population variation in MHC variants correlates positively with host immunocompetence, but this variation decreases as pathogen richness increases.

Conclusions:

• Factors beyond pathogen richness are crucial for understanding the diversity of MHC gene numbers in vertebrates.
• Counterintuitively, reduced pathogen exposure can lead to greater genetic variance in host fitness, impacting theories like Hamilton-Zuk.
• The interplay between pathogen diversity, evolution, and host costs shapes immune gene evolution.