Clustering of C‐Type Lectin Natural Killer Receptor‐Like Loci in the Bony Fish Oreochromis niloticus

Abstract

The genome of the cichlid (teleost) fish Oreochromis niloticus contains a set of genes which encode group V C-type lectin proteins homologous to the mammalian NKG2/CD94 family of natural killer (NK) cell receptors. To determine the genomic organization of these killer cell-like receptor (KLR) genes, an O. niloticus BAC library was screened with a cDNA probe derived previously from an expressed sequence tag of the related cichlid species Paralabidochromis chilotes. Four distinct KLR-bearing BAC clones were analysed, three of which could be assembled into a contig. One of the clones was sequenced in its entirety, whereas the others were partially sequenced to identify the KLR loci borne by them. Altogether, 28 distinct KLR loci were identified, of which at least 26 occupy a single chromosomal region, the KLR complex. One half of the loci appear to be occupied by pseudogenes. Compared to the human NK cell receptor complex, the Oreochromis KLR complex is more compact and, apart from transposons, appears to contain only KLR loci. The gene density of the complex is one KLR locus per 18 kb of sequence. All the KLR loci constituting the complex are derived from a single most recent common ancestor, which is estimated to have existed 7.7 million years ago. The 180 kb of the determined sequence is a mosaic of blocks of similar segments reflecting a complex history of duplications, deletions and rearrangements. The transposons found in the sequenced part belong to the TC1, Xena, CR1 and TX1 families.

Comparative Genomics of Natural Killer Cell Receptor Gene Clusters

“…While these genes encode an Ig domain, there is a cluster of C-type lectins encoded within this larger cluster [103,104]. Another bony fish, Oreochromis niloticus, possesses a KLR region, containing 26 genes, though more compact than its human counterpart [105]. Other teleosts have NKC genes, including Paralabidochromis chilotes [106] and rainbow trout [107], demonstrating that some of these genes arose in an ancestor common to both humans and bony fish earlier in the gnathostome lineage.…”

Cytotoxic activities of fish leucocytes

“…On the genetic level the putative sequence of the so called NK cell enhancing factor (NKEF) has been sequenced in rainbow trout [46] and common carp [47]. Recently, sequences encoding group V C-type lectin homologous to the mammalian NKG2/CD94 family of NK cell receptors have been discovered in cichlid fishes [48,49]. In mammals, NKG2 receptors costimulate multiple NK activation receptors [50].…”

NK gene complex dynamics and selection for NK cell receptors

“…Though not shown experimentally, one might speculate that cKLR sequences are expressed by killer cells in organs of the fish where innate immune effector function(s) are needed. As with CD94/NKG2 sequences in mammalian species, cKLR genes are also clustered in a narrow genomic NKC-like region [16, 17]. Altogether, there is substantial evidence indicating clustered NKR genes and gene families are an important genomic component retained in a diverse range of vertebrate species.…”

“…Direct sequencing of BAC clones containing cKLR sequences further revealed that the CD94/NKG2-related gene sequences are clustered together in the cichlid fish genome [17]. Though related sequences have so far remained elusive in the trout, genetic mapping strategies based on an NK-like trait (i.e.…”

“…Though the cichlid KLR sequences are most related to mammalian CD94/NKG2 sequences, orthologous matches are not apparent. Instead, fish and mammalian KLR genes are likely to have arisen independently through duplications of distinct ancestral genes in a paralogous fashion [16, 17]. Further, the cichlid NKC might only contain genes for Group V-like activation-type KLR members, and without other CLEC-related gene sequences.…”