Allelic diversity at the primate major histocompatibility complex DRB6 locus

Area of Science:

• Genetics
• Evolutionary Biology
• Immunogenetics

Background:

• The human leukocyte antigen (HLA)-DRB6 gene, also known as DRB sigma/V1, is found in a limited subset of human HLA haplotypes (approx. 26%).
• In contrast, the DRB6 gene is conserved across various primate species.

Purpose of the Study:

• To investigate the evolutionary history and distribution of the HLA-DRB6 gene in humans and other primates.
• To explore the implications of DRB6 gene presence and variation for understanding major histocompatibility complex (MHC) evolution.

Main Methods:

• Comparative sequence analysis of HLA-DRB6 exon-2 across different primate species.
• Phylogenetic analysis to infer evolutionary relationships and divergence times.

Main Results:

• The HLA-DRB6 gene was detected in all tested chimpanzees, gorillas, and orangutans, indicating its ancient presence in apes.
• Sequence data revealed high similarity between DRB6 sequences from different species, supporting the trans-species theory of MHC polymorphism.
• Evidence suggests that DRB6 may be one of the oldest genes in the DRB family, diverging early from the ancestral DRB gene.
• The apparent loss of DRB6 in some human haplotypes suggests recent and active evolutionary changes in the human DR genome compared to class I or III genes.

Conclusions:

• The HLA-DRB6 gene exhibits a distinct evolutionary pattern, being conserved in apes but variably present in humans.
• The findings support the trans-species evolution of MHC genes and suggest DRB6 is an ancient DRB family member.
• Recent evolutionary dynamics in the human DR genome are highlighted by the differential presence of the DRB6 gene.