Major histocompatibility complex complement (MHC) Bf alleles show trans species evolution between man and chimpanzee

Area of Science:

• Immunogenetics
• Evolutionary Biology
• Human Genetics

Background:

• Single allele statistics in Human Leukocyte Antigen (HLA) and disease studies have yielded limited insights into disease pathogenesis over the past 40 years.
• Alternative approaches are needed to understand the complex interplay between immune genes and disease.

Purpose of the Study:

• To revisit complement alleleism in humans and primates for studying the Major Histocompatibility Complex (MHC) and disease associations.
• To investigate complotypes and extended MHC haplotypes to explain the evolutionary selection of immune response genes within the MHC.
• To explore the potential role of these genes in jointly preventing microbial attacks and autoimmunity.

Main Methods:

• Sequencing of exons 1 to 6 of the Ba fragment of the chimpanzee Bf gene.
• Identification and characterization of a novel chimpanzee Bf allele, provisionally named Patr-Bf*A:01.
• Comparison of the novel chimpanzee allele with human Bf alleles and single nucleotide polymorphisms (SNPs).

Main Results:

• A new chimpanzee Bf allele, Patr-Bf*A:01, was identified, differing by a specific codon in exon 2.
• Patr-Bf*A:01 is identical to an infrequent human Bf allele (SNP rs641153), indicating strong evolutionary pressure on trans-specific alleles.
• This marks the first description of a complement MHC class III allele exhibiting trans-species evolution, unlike previously reported class I and II alleles.

Conclusions:

• Complement alleleism, complotypes, and extended MHC haplotypes may offer more comprehensive insights into MHC-related diseases than single MHC marker studies.
• The findings highlight the evolutionary conservation and potential functional significance of complement genes within the MHC.
• Further research into complement alleleism is proposed for a deeper understanding of immune response and disease associations.