The paradox of MHC-DRB exon/intron evolution: alpha-helix and beta-sheet encoding regions diverge while hypervariable...

Area of Science:

• Immunogenetics
• Molecular Evolution
• Comparative Genomics

Background:

• The Major Histocompatibility Complex (MHC) plays a crucial role in immune responses.
• MHC-DRB genes are highly polymorphic and essential for antigen presentation.
• Simple repetitive elements in introns are found across species, but their evolutionary role is debated.

Purpose of the Study:

• To determine caprine and ovine MHC-DRB exon 2 sequences and adjacent intronic repeats.
• To investigate the evolutionary history of MHC-DRB sequences in ungulates.
• To explore the potential role of intronic repetitive elements in the evolution of MHC-DRB genes.

Main Methods:

• DNA sequencing of MHC-DRB exon 2 and flanking introns in goats and sheep.
• Phylogenetic analysis of coding (alpha-helices, beta-sheets) and noncoding (intronic repeats) regions.
• Comparative analysis of sequence variations and evolutionary patterns.

Main Results:

• Sequenced 21 caprine and 13 ovine MHC-DRB exon 2 sequences with adjacent introns containing (gt)n(ga)m repeats.
• Identified conserved (gt)n(ga)m repeat structures across mammals, with variations in dinucleotide composition.
• Phylogenetic analyses suggest distinct evolutionary trajectories for alpha-helices and beta-pleated sheets.
• DRB beta-sheet sequences and intronic repeats showed coevolutionary patterns similar to humans.
• Alpha-helices and C-terminal regions exhibited independent evolution.

Conclusions:

• MHC-DRB beta-sheet encoding sequences and adjacent intronic repeats in ungulates exhibit coevolution, mirroring patterns in humans.
• The conserved (gt)n(ga)m intronic repeats may play a role in facilitating genetic exchange mechanisms like double-recombination or gene conversion.
• Distinct evolutionary rates for different regions of the DRB gene suggest a complex evolutionary process involving both conserved and rapidly evolving elements.