Ancient trans-species polymorphism at the Major Histocompatibility Complex in primates

Area of Science:

• Evolutionary biology
• Immunogenetics
• Primate genomics

Background:

• Major Histocompatibility Complex (MHC) genes are vital for immune defense, exhibiting high genetic diversity due to strong selective pressures.
• Trans-species polymorphism (TSP), the sharing of allelic lineages across species, is observed in MHC genes but its extent in primates is not fully understood.

Purpose of the Study:

• To investigate the evolutionary history and extent of trans-species polymorphism (TSP) within individual primate MHC genes.
• To understand the retention of MHC genes and allelic lineages across primate speciation events.

Main Methods:

• Utilized Bayesian phylogenetic methods to analyze genetic variation within 17 MHC genes (Class I and Class II, classical and non-classical).
• Examined nucleotide and amino acid sequence evolution, focusing on peptide-binding domains.

Main Results:

• Found strong evidence of ancient TSP in 7 out of 10 classical MHC genes, including between humans and Old World monkeys for MHC-DQB1.
• Observed rapid evolution in nucleotides encoding peptide-binding domains, with rapidly evolving sites linked to autoimmune and infectious disease associations.
• Demonstrated the long-term persistence of deeply divergent MHC lineages, up to 31 million years.

Conclusions:

• Primate MHC evolution is characterized by both the long-term maintenance of ancient allelic lineages and rapid short-term evolution driven by peptide-binding diversity.
• These complex selective forces shape MHC diversity, influencing immune responses and disease susceptibility.