Structure of the catfish IGH locus: analysis of the region including the single functional IGHM gene

Abstract

The catfish IGH locus is large ( approximately 1 Mb) and complex, having undergone multiple internal duplications and transpositions. To define the structure of the locus that contains the single expressed IGHM gene, two overlapping bacterial-artificial-chromosome (BAC) clones spanning the most 3' end of the channel catfish immunoglobulin heavy (IGH) chain locus have been completely sequenced. The analyses created a contig of 257,153 bp containing 55 VH, 6 D, 12 JH genes and the IGH constant region genes encoding the functional secreted and membrane forms of IgM and the membrane form of IgD. This analysis revealed three major features. First, no C-region genes were found aside from the previously described IGHM1 and IGHD1, with the latter gene being the most 3' C-region gene of the catfish IGH locus. There was no evidence in the region sequenced for genes that could encode an Ig class similar to the IgZ/IgT described in zebrafish, trout and pufferfish. Second, there are a high number of VH pseudogenes, 28 out of 55 (51%). In contrast, the entire zebrafish IGH locus has 40 functional VH genes and eight pseudogenes (17%). Third, an internal duplication of a 52.4-kb block of VH genes has occurred. These observations suggest that the IGH locus of teleost fish varies significantly from species to species in the diversity of C-region genes as well as the numbers of genes encoding V regions.

Ig heavy chain genes and their locus in grass carp Ctenopharyngodon idella

“…However, the complete composition of V H genes in the IgH loci has been reported only in zebrafish, three-spined stickleback and channel catfish, with 47, 49 and 55 V H genes identified, respectively [22,24,29]. It seems possible that the number of V H genes may vary in different species of teleost fish.…”

“…The catfish IgH locus is a translocon-type with three d genes linked to a m gene or pseudogene [28,29], being thus different from that in zebrafish, rainbow trout, fugu and grass carp. It is suggested that the organization of the IgH locus in different species of teleost fish may vary at least to some extent, as illustrated for the above five species of teleost fish.…”

“…It has been suggested that some Ig isotypes may be just another name of a formerly reported Ig isotype; for example, IgZ and IgT may be of the same isotype in fish, and the newly identified IgO in platypus [4] has been considered as IgY, as it shares characteristics with IgY [5]. Furthermore, genomic organization of IgH locus has also been identified in several species of teleost fish, such as in zebrafish [22], rainbow trout [23], fugu [25], channel catfish (Ictalurus punctatus) [28,29] and three-spined sticklebacks [24]. The genome organization of IgH locus in channel catfish is a translocon arrangement, with three d genes linked to an m gene or pseudogene, and the loci in zebrafish and fugu follow the pattern of genomic organization: VneDneJneCz/s/C H eDneJneCmeCd [22,25,28,29].…”

“…Furthermore, genomic organization of IgH locus has also been identified in several species of teleost fish, such as in zebrafish [22], rainbow trout [23], fugu [25], channel catfish (Ictalurus punctatus) [28,29] and three-spined sticklebacks [24]. The genome organization of IgH locus in channel catfish is a translocon arrangement, with three d genes linked to an m gene or pseudogene, and the loci in zebrafish and fugu follow the pattern of genomic organization: VneDneJneCz/s/C H eDneJneCmeCd [22,25,28,29]. The organization of the IgH locus in rainbow trout is, in general, similar to that of zebrafish and fugu, except that two V H genes were found downstream of the Cz [23].…”

Targets of somatic hypermutation within immunoglobulin light chain genes in zebrafish

“…Point mutations similar to those at V H WRCH sequences have also been found at the WRCH within switch regions in mice, suggesting a common AID targeting method for both SHM and CSR. 41,42 Given that SHM has been found in all vertebrates including fish, whereas CSR appears limited to amphibians, birds and mammals [43][44][45][46][47] , it appears that SHM evolved earlier than CSR. In mammals, immunoglobulin switch regions appear to have further diverged to incorporate additional features, such as R-loop forming ability and cis-acting regulatory regions, which may serve to increase the overall efficiency of CSR.…”