A comparative analysis of genetic diversity at Mhc DRB loci in some ruminant species

In this thesis the highly polymorphic bovine Mhc class IIDRB3 locus (BoLA-DRB3) and homologous loci in other ruminant species have been characterized. The aim of the work was to broaden the knowledge about the evolution and significance of Mhc diversity. DRB exon 2 polymorphism was investigated by single strand conformation polymorphism (SSCP) analysis, and by DNA sequence analysis. The DRB exon 2 sequences showed considerable variation in cattle, bison, reindeer, and red deer whereas, moose, muscox, roe deer, and fallow deer, exhibited low or no polymorphism. Both European and North American populations of moose exhibit very low levels of genetic diversity at the expressed DRB1 locus. The data imply that the moose has lost Mhc diversity in a population bottleneck prior to the divergence of the two subspecies, more than 100,000 years ago. Thus, a restricted Mhc diversity may be compatible with long-term survival. A comparative analysis ofthe DRB3 polymorphism in bison and cattle revealed an extensive sharing of sequence motifs. The result clearly showed a trans-species persistence of sequence motifs in the two species. A deletion of codon 65 was found in three BoLADRB3 alleles, and in one roe deer DRB1 allele. It could not be resolved whether the presence of the deletion in cattle and roe deer was due to common ancestry or parallel mutations. Analysis of the pattern of sequence polymorphism in ruminant DRB alleles suggests that both positive selection for polymorphism and interallelic recombination have contributed to the generation of Mhc diversity at this locus