Using three genomic phage libraries, we isolated 26 clones from the ze
brafish MHC class II B region. By restriction mapping, the clones coul
d be arranged into six clusters, most clusters consisting of several o
ver lapping clones. The combined clusters cover a total of 161 kb of t
he zebrafish class II region. Hybridization with specific probes demon
strated the presence in the clusters of two class II A and six class I
I B genes. Sequencing of the B genes revealed that they represented si
x different families of class II loci. Only two of the class II B and
one of the class II A genes are complete; the others are truncated pse
udogenes. Only one of the class II B loci shows extensive restriction
fragment length polymorphism. This is also the only locus found to be
transcribed in organs with large numbers of lymphoid or myeloid cells.
The zebrafish class II genes have promoter regions with sequence elem
ents found previously in mammalian genes and known to be involved in r
egulation of expression. The exon-intron organization of the zebrafish
class II genes is similar to that of the mammalian genes, but the int
rons are characteristically short, ranging in length from 74 to 362 bp
. The distances between A and B genes in a given pair are also short,
but the distances between B genes are as long as or longer than those
between mammalian class II B genes. All of the zebrafish class II B ge
nes appear to have arisen by duplication and diversification of a sing
le ancestral B gene after the separation of bony fishes from other ver
tebrate taxa. (C) 1994 Academic Press, Inc.