A "minimal essential Mhc" and an "unrecognized Mhc": two extremes in selection for polymorphism

Area of Science:

• Immunogenetics
• Evolutionary Biology
• Comparative Genomics

Background:

• The high polymorphism of mammalian major histocompatibility complex (Mhc) molecules is traditionally attributed to pathogen-driven selection.
• However, evidence for specific pathogen resistance linked to Mhc haplotypes is scarce, and selection pressures, like in human malaria, appear weak.
• Mammalian Mhc complexity and redundancy may obscure direct selection signals for disease resistance.

Purpose of the Study:

• To investigate the evolutionary forces driving Mhc polymorphism by comparing mammals with other vertebrates.
• To explore alternative hypotheses for high Mhc polymorphism, including accumulating, merging, and boosting mechanisms.
• To understand the functional consequences of Mhc diversity in different species.

Main Methods:

• Comparative analysis of Mhc structure and polymorphism across mammals, birds (chickens), and amphibians (salamanders).
• Investigation of allograft rejection as an indicator of Mhc function.
• Isolation and characterization of axolotl Mhc molecules and assessment of T cell stimulation.
• Determination of peptide motifs for chicken class I Mhc molecules.

Main Results:

• Mammals exhibit complex and redundant Mhc, complicating direct selection studies.
• Birds (chickens) possess a simpler Mhc with strong allograft rejection and clear associations between Mhc haplotypes and viral disease resistance.
• Salamanders display low Mhc polymorphism and weak allograft rejection, suggesting T cells may not effectively recognize their Mhc molecules.
• Specific peptide motifs for chicken Mhc class I molecules were identified, potentially explaining disease associations.

Conclusions:

• High Mhc polymorphism in mammals may not be solely driven by recent pathogen resistance.
• The simplified Mhc of birds suggests strong selection on individual genes for pathogen resistance.
• Low Mhc polymorphism in salamanders might result from poor T cell recognition rather than relaxed selection.
• Understanding Mhc evolution requires considering species-specific genetic architectures and immune system interactions.