Evidence for the genomic organization of human lambda light chain joining (J) region gene segments is presented. A mouse Jλ probe was used in Southern hybridizations to localize joining region sequences in a cosmid clone containing the genomic cluster of six human lambda constant (C) region gene segments. The results of these hybridizations suggest the presence of at least one J gene segment upstream from each constant region gene segment. The DNA sequences indicate that the human JλI, Jλ2, and Jλ3 gene segments have consensus nonamer and heptamer sequences, proposed to be involved in V-J joining, are capable of encoding the known amino acid sequences for the respective J peptides, and have a sequence which could give γ functional RNA splice site at the end of their coding regions. Our data show that a single functional J is located ∼ 1.3 or 1.6 kb upstream of each of the Cλ gene segments known to encode the Mcg, Kern- Oz-, and Kern-Oz+ isotypes. Therefore, the gene organization of this region of the human lambda locus is J1 CI -J2C2-J3C3. The DNA sequences of Jλ1, Jλ2, and Jλ3 presented in this paper establish that a single Jλgene segment precedes each expressed Cλ gene segment, and support a model for the evolution of the human λ JC clusters where JICI and J2C2-J3C3. arose from different ancestral JC units.
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