Tracing the evolution of H-2 D region genes using sequences associated with a repetitive element

Area of Science:

• Immunogenetics
• Evolutionary biology
• Molecular genetics

Background:

• The murine Major Histocompatibility Complex (MHC) class I genes are categorized into K, D, Qa, and T1a subfamilies, likely originating from a common ancestor through gene duplication.
• The H-2D and H-2L genes contain a B2 SINE element in their 3' untranslated region, serving as a genetic marker.

Purpose of the Study:

• To investigate the evolutionary divergence of murine MHC class I gene subfamilies.
• To determine the evolutionary relationship between D region genes (H-2D, H-2L) and other class I gene family members.
• To assess if variations in Qa and T1a region gene numbers result from recent duplications of D region genes.

Main Methods:

• Utilized oligonucleotide probes specific for a B2 SINE element inserted in H-2D and H-2L genes.
• Performed hybridization analyses on recombinant cosmid and genomic DNA.
• Examined gene copy number variation across different mouse strains and species within the Mus genus.

Main Results:

• Hybridization data indicate that the D region genes (H-2D, H-2L) genetically separated from other class I genes 12 to 14 million years ago.
• The B2 SINE insertion in the D region appears to have become fixed in the ancestral Mus domesticus population during this divergence period.
• No evidence supports the hypothesis that Qa and T1a region gene number variations arise from recent duplications of H-2D and H-2L genes.

Conclusions:

• The murine MHC class I gene family underwent significant genetic divergence over 12 million years ago.
• The evolutionary history of class I gene number variation is complex and not solely explained by recent duplications of D region genes.