Characterization and trans-species evolution of Mhc genes in the zebrafish (Danio rerio)

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)


Microbiology and Immunology

First Committee Member

Jan Klein - Committee Chair


One of the characteristic features of Mhc polymorphism in mammals is the existence of allelic lineages shared by related species. This trans-species polymorphism has thus far only been well documented only in primates, rodents, and artiodactyls. In this study, Mhc genes of the zebrafish (Danio rerio) and two related species Danio albolineatus and Danio malabaricus were investigated, to provide evidence for trans-species evolution in teleost fish. Trans-species evolution was observed in these species for allelic lineages at both the Mhc Class II A and B loci. Large genetic distances were observed, especially for lineages at the B locus. Most of the polymorphism was found at the peptide binding region (PBR) and is apparently maintained by balancing selection. The sharing of these unique Mhc features by teleost fish and mammals suggest that the main function of the Mhc has not changed during its last 400 million years of evolution.The organization of Mhc genes is also of paramount importance in understanding how the vertebrate immune system evolved. A zebrafish BAC library was screened, to the map Mhc genes of zebrafish. Mhc genes from 3 Class I A loci, 6 Class II B loci, and 1 Class II A locus were identified. Only the DAA gene was found to be linked to the DAB gene, the products of which are believed to form the only functional Class II molecule in the zebrafish. None of the other Mhc genes were physically linked, through utilization of BAC clones which average 100 kb in size. Linkage was established for a Class I A gene and Lmp7, which codes for a $\beta$ subunit of the 20S proteasome complex. Recently, the Lmp7 gene was determined to be linked to a Class I A gene in the amphibian, with both genes located in the Class II region. Although the Lmp7/Class I linkage seems to be maintained in the zebrafish, ClassI/ClassII linkage in this organism is not. This suggests that the Mhc complex in teleost fish may be present in a primordial type of organization, though further experiments need to be done to confirm it.


Biology, Genetics; Health Sciences, Immunology

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