L V J C

1 kb

v, Vr v„ v%„v, DdutJW c^Cs Cy Cri cai c£c? cy cEiq?

( mill [] Hill) (I—HI—>"—• " --4-H-[)-■-■—■—■-{ }-■—■—I—m-

20 kb

Shark

Shark

Figure 2 Physical maps of (A) X light chain and (B) |x heavy chain loci of human, chicken and shark. Curly brackets {} indicate unknown distances between gene segments on the same chromosome. Dotted lines indicate that it is not even known if the gene segments are on the same chromosome. The organization and distances of gene segments within parentheses () is unknown. i|i indicates a pseudogene. The maps are adapted from Lai et a/ (1989), McCormack and Thompson (1990), Shamblott and Litman (1989) and Hohman, Schluter and Marchalonis (1995).

1 kbt

Figure 2 Physical maps of (A) X light chain and (B) |x heavy chain loci of human, chicken and shark. Curly brackets {} indicate unknown distances between gene segments on the same chromosome. Dotted lines indicate that it is not even known if the gene segments are on the same chromosome. The organization and distances of gene segments within parentheses () is unknown. i|i indicates a pseudogene. The maps are adapted from Lai et a/ (1989), McCormack and Thompson (1990), Shamblott and Litman (1989) and Hohman, Schluter and Marchalonis (1995).

association of these elements in agnathan cyclostomes and protochordates remains to be determined.

The basic gene arrangement as illustrated by the human X. and p chains is the type of configuration adopted by mammals, amphibians (frogs) and teleosts (fish). For each gene cluster, a large number of V regions is associated with a limited number of C regions. The whole V region repertoire is available for each C region. There are also numerous J and D (for p. chain) segments. Diversity is generated by randomly combining together through DNA rearrangement events single V(D)J elements with a C region to form a functional gene. In the chicken, there is only a single set of functional genes and all antibodies are derived from the same rearrangement event. Diversity is generated by gene conversion events between the single functionally rearranged V region and numerous V region pseudogenes. The arrangement in the shark is again quite different. Whereas in the situations described above diversity is generated by having many V regions or pseudo-V genes associated with a few C regions, in the shark there is only a single V for each C. These are associated in short V(D)JC regions and each of these clusters is duplicated many times in the genome. Interestingly, V(D)J rearrangement still has to occur to generate a functional gene and the mechanism for this is very similar to that in mammals.

Unexpected multiplicity of immunoglobulins in lower vertebrates

Until recently there was a general consensus that, although cartilaginous fishes, such as sharks and rays, had the capacity to produce antibodies very-similar to mammalian IgM, their immune systems were extremely primitive. They were thought to lack other immunoglobulin isotypes, the capacity to show immune maturation following secondary immunization and functional thymus-derived lymphocytes. However, it was recently established using recombinant technology that sharks possess a second major immunoglobulin class, termed IgW or IgNARC (new-antigen receptor from cartilaginous fish), that has a

Table 1 Comparison of amino acid sequences of heavy chain variable and jjl chain constant regions of human, chicken, clawed toad and shark. Identities are shown boxed or circled. The alignments were carried out according to the procedure of Feng and Doolittle, with sequence data referenced in Marchalonis and Schlüter (FASEB Journal, 1989). VH and CH domains are placed with reference to the human sequence according to Kabat. Sources of sequences: a) human - myeloma protein gel from the Genbank database; b) chicken - V region is cDNA clone 3W-25 from Reynaud et al (1989), C region is from the Genbank database; c) clawed toad (Xenopus) - from Schwager et al (1989); d) horned shark - V region is genomic clone 2809, DJC region is cDNA clone 12622 from Kokubu et al (1988). Citations are given in Marchalonis and Schlüter (1989). Stars denote complete conservation among the four species

Human Chicken Toad Shark

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