Mapping of Mhc class I and class II regions to different linkage groups in the zebrafish, Danio rerio

Abstract

The mammalian major histocompatibility complex (Mhc) consists of three closely linked regions, I, II, and III, occupying a single chromosomal segment. The class I loci in region I and the class II loci in region II are related in their structure, function, and evolution. Region III, which is intercalated between regions I and II, contains loci unrelated to the class I and II loci, and to one another. There are indications that a similar Mhc organization exists in birds and amphibians. Here, we demonstrate that in the zebrafish (Danio rerio), a representative of the teleost fishes, the class II loci are divided between two linkage groups which are distinct from the linkage group containing the class I loci. The beta2-microglobulin-encoding gene is loosely linked to one of the class II loci. The gene coding for complement factor B, which is one of the region III genes in mammals, is linked neither to the class I nor to the class II loci in the zebrafish. These results, combined with preliminary data suggesting that the class I and class II regions in another order of teleost fish are also in different linkage groups, indicate that close linkage of the two regions is not necessary either for regulation of expression or for co-evolution of the class I and class II loci. They also raise the question of whether linkage of the class I and class II loci in tetrapods is a primitive or derived character.

A Contig Map of theMhcClass I Genomic Region in the Zebrafish Reveals Ancient Synteny

“…The BS1 clone and the B contig could be, therefore, either paralogues of a contig A segment or contig A haplotypes with rearranged genes. Arguing against the former possibility is the observation that even though genetic tests indicate that the UAA/UEA and the UBA/UCA loci are very closely linked (18), the UBA/UCA loci are absent from a YAC clone library in which three YAC clones were found that bear the UEA/UDA loci (together encompassing Ͼ500 kb of sequence). The B contig and possibly also the BS1 clone may therefore represent haplotypic variants of part of the A contig.…”

“…In contrast to the situation in the tetrapods, in the zebrafish, a representative of the teleost (bony) fishes, the class I loci are not linked to the class II loci (18), the class II loci are split among three linkage groups (18), and the TAP, as well as the PSMB loci are closely linked to the class I loci (19); in mammals they are located in the class II region (20,21). A survey of different teleost orders indicates that a similar situation to that in the zebrafish exists in other bony fishes (22).…”

“…Attempts to link the class I contig with the group of RXRD-bearing clones by chromosome walking failed, however. In fact, in a study still in progress (B. W. Murray and R. Geisler, unpublished observations), the RXRD locus could be mapped, using a panel of zebrafish radiation hybrids, to linkage group 16, whereas the class I loci are known to be in linkage group 19 (18). Therefore, the mapping of the RXRD locus by Gongora et al (29) must have been in error.…”

Independent Duplications of Bf and C3 Complement Genes in the Zebrafish

“…Both adults and haploid embryos were derived from zebrafish (Danio rerio) laboratory stocks maintained at the Max-Planck-Institut für Biologie, Tübingen. Haploid embryos were produced as described previously [27].…”

“…DNA sequencer (Pharmacia Biotech). The primers Tu1279 (sense) and Tu1280 (antisense), corresponding to exons 3 and 4 of the zebrafish Bf genes have been described previously [27]. To obtain longer sequences of the new Bf gene (see below) from the cDNA library, two specific primers for this gene were designed: BfN1 (5 0 -CAGGACAGTGATCAGAGTCACGTT-3 0 , antisense, codons 128-136) and BfN3 (5 0 -GGTAACCACTTATTC-GTGTAATC-3 0 , sense, codons 94-102), and used in combination with anchor primers in both arms of the l gt10 vector: gt10-F (5 0 -TTGAG-CAAGTTCAGCCTGGTTAAG-3 0 , sense) and gt10-R (5 0 -CTTATGAG-TATTTCTTCCAGGGTA-3 0 , antisense).…”