Structure of the human immunoglobulin Cε2 gene, a truncated pseudogene: Implications for its evolutionary origin

Cloning of the overlapping DNA fragments together with Southern hybridization experiments showed the organization of the human Cε and Cα gene cluster as 5'-Cε2-14 kilobases-Cα1- - - -Cε1-13 kilobases-Cα2-3'. Comparison of the nucleotide sequences of the Cε1 and Cε2 genes revealed that four deletions have taken place in the Cε2 gene and its flanking regions. The three deleted regions in the 5' side of the Cε2 gene are partially filled with shorter inserted sequences. One of them has removed the CH1 and CH2 exons and a portion of the epsilon switch (Sε) region. The Sε region and the CH4 exon still retain the functional structures, whereas the CH3 exon has been inactivated by deleting its 5' intervening sequence necessary for splicing. The tetranucleotide T-G-G-G (or T-G-G-C), which is usually found in close proximity of the class-switch recombination sites in mouse myelomas, is located 5' to the three deletion sites. The results imply that the mechanism responsible for the heavy chain class-switch recombination might be relevant to the evolutionary mechanism of creation of the truncated Cε2 gene. The other deletion in the 3' flanking region of the Cε2 gene may be due to slipped mispairing of the short direct repeat (C-C-C-C-C) at both ends