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MHC-DRB allelic sequences incorporate distinct intragenic trans-specific segments
L K Gaur1, G T Nepom, K E Snyder
1Puget Sound Blood Center, Seattle, Washington, USA. gaur@u.washington.edu
Tissue Antigens
|April 1, 1997
Summary
The study reveals that specific conserved sequence motifs in primate MHC-DRB genes, particularly in HVRIII, show trans-species origins, while other regions like HVRI exhibit more species-specific variation, indicating distinct evolutionary paths.
Area of Science:
- Evolutionary genetics
- Immunogenetics
- Primate genomics
Background:
- Primate Major Histocompatibility Complex (MHC)-DRB genes contain hypervariable regions (HVRs) crucial for genetic and evolutionary analyses.
- The trans-species hypothesis suggests MHC alleles are shared across species, implying ancient origins.
- Understanding these evolutionary relationships is key to primate genetic diversity studies.
Purpose of the Study:
- To evaluate the trans-species hypothesis in macaque and baboon MHC-DRB genes.
- To investigate the evolutionary conservation of sequence motifs in primate MHC-DRB genes.
- To differentiate between species-specific and trans-species evolutionary patterns in MHC-DRB regions.
Main Methods:
- Oligotyping and sequencing of 87 nonhuman primate DRB alleles.
- Comparative analysis of sequence motifs in the first hypervariable region (HVRI) and HVRIII.
- Hybridization and sequencing to detect conserved motifs.
Main Results:
- Remarkable conservation of sequence motifs in the HVRIII region (codons 60-79) was observed, even in species diverged 50 million years ago.
- Fixed HVRIII motifs were found on diverse genetic backgrounds, suggesting segmental motifs, not whole alleles, are trans-specific.
- HVRI analysis identified lineage assignments but also revealed numerous nonhuman sequences lacking human homologs and exhibiting intraspecies variation.
- Distinct evolutionary mechanisms for HVRI and HVRIII suggest different histories for nucleotide conservation.
Conclusions:
- The trans-species hypothesis is supported by conserved HVRIII motifs, indicating segmental elements are ancient and shared across primate lineages.
- HVRI exhibits a mix of trans-species and species-specific motifs, suggesting varied evolutionary pressures and histories.
- Primate MHC-DRB genes possess distinct evolutionary trajectories for different hypervariable regions, impacting lineage assignment and evolutionary interpretations.