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

Hisajima, Hiroshi and Nishida, Yasuyoshi and Nakai, Sumiko and Takahashi, Naoki and Ueda, Shintaro and Honjo, Tasuku (1983) Structure of the human immunoglobulin Cε2 gene, a truncated pseudogene: Implications for its evolutionary origin. Proceedings of the National Academy of Sciences of the United States of America, 80 (10). pp. 2995-2999. ISSN 0027-8424.

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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.

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Additional Information:© 1983 by the National Academy of Sciences. Communicated by L. L. Cavalli-Sforza, January 28, 1983. We are grateful to Dr. T. Maniatis (Harvard University) for a human DNA library and to Drs. A. Bothwell and D. Baltimore (Massachusetts Institute of Technology) for a mouse α-cDNA clone. We thank F. Oguni for her excellent assistance in preparing the manuscript. This investigation was supported in part by grants from the Ministry of Education, Science and Culture and from the Ministry of Health and Welfare of Japan. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Subject Keywords:Cε-Cα linkage; nucleotide sequence determination; common tetranucleotide; class-switch recombination
Issue or Number:10
Record Number:CaltechAUTHORS:HISpnas83
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7642
Deposited By: Tony Diaz
Deposited On:16 Mar 2007
Last Modified:02 Oct 2019 23:44

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