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一种系统发育上原始的脊椎动物中存在广泛的恒定区基因家族，这表明免疫球蛋白的复杂性又增加了一层。

Extensive families of constant region genes in a phylogenetically primitive vertebrate indicate an additional level of immunoglobulin complexity.

作者信息

Kokubu F, Hinds K, Litman R, Shamblott M J, Litman G W

出版信息

Proc Natl Acad Sci U S A. 1987 Aug;84(16):5868-72. doi: 10.1073/pnas.84.16.5868.

DOI:10.1073/pnas.84.16.5868
PMID:3475706
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC298964/
Abstract

A homologous probe for the constant region of the Heterodontus francisci (horned shark) immunoglobulin heavy chain was used to screen a genomic DNA library constructed in bacteriophage lambda, and a large number of independent clones were recovered. Their hybridization patterns with segment-specific probes are consistent with the close linkage of heavy-chain constant (CH), joining (JH), and variable (VH) gene segments. Differences in the nucleotide sequences of the first CH exon of five genes primarily are localized to 5' positions; extended regions of sequence identity are noted at 3' positions. The predicted amino acid sequences of each gene are different and are related distantly to the corresponding regions of higher vertebrate immunoglobulins. Gene-specific oligodeoxynucleotide probes were used to establish that at least three of the five genes are transcriptionally active. Quantitative gene titration data are consistent with the large numbers of genes suggested by the library screening analyses. In this representative early vertebrate, it appears that (VH-diversity-JH) segments are associated with individual constant region genes that can differ at the predicted protein level.

摘要

使用一个针对弗朗西斯异齿鲨（角鲨）免疫球蛋白重链恒定区的同源探针，筛选构建于噬菌体λ中的基因组DNA文库，回收了大量独立克隆。它们与片段特异性探针的杂交模式与重链恒定区（CH）、连接区（JH）和可变区（VH）基因片段的紧密连锁一致。五个基因的第一个CH外显子的核苷酸序列差异主要位于5'端；在3'端发现了延伸的序列同一性区域。每个基因的预测氨基酸序列不同，并且与高等脊椎动物免疫球蛋白的相应区域有较远的亲缘关系。使用基因特异性寡脱氧核苷酸探针确定五个基因中至少有三个具有转录活性。定量基因滴定数据与文库筛选分析所提示的大量基因一致。在这个具有代表性的早期脊椎动物中，似乎（VH-多样性-JH）片段与在预测蛋白质水平上可能不同的单个恒定区基因相关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/298964/bf7635381e57/pnas00331-0371-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/298964/d64bd7f83dbd/pnas00331-0368-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/298964/f838867bbc3e/pnas00331-0370-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/298964/13020ae1b491/pnas00331-0371-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/298964/a761128a426e/pnas00331-0371-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/298964/bf7635381e57/pnas00331-0371-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/298964/d64bd7f83dbd/pnas00331-0368-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/298964/f838867bbc3e/pnas00331-0370-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/298964/13020ae1b491/pnas00331-0371-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/298964/a761128a426e/pnas00331-0371-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/298964/bf7635381e57/pnas00331-0371-c.jpg

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Extensive families of constant region genes in a phylogenetically primitive vertebrate indicate an additional level of immunoglobulin complexity.一种系统发育上原始的脊椎动物中存在广泛的恒定区基因家族，这表明免疫球蛋白的复杂性又增加了一层。
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本文引用的文献

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Organization of the constant-region gene family of the mouse immunoglobulin heavy chain.小鼠免疫球蛋白重链恒定区基因家族的组织
Cell. 1982 Mar;28(3):499-506. doi: 10.1016/0092-8674(82)90204-5.
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Organization of four mouse lambda light chain immunoglobulin genes.四个小鼠λ轻链免疫球蛋白基因的组织
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Two mRNAs can be produced from a single immunoglobulin mu gene by alternative RNA processing pathways.通过可变RNA加工途径，可从单个免疫球蛋白μ基因产生两种mRNA。
通过 RNA 加工和同种型转换实现鲨鱼 IgW C 区的多样化。
J Immunol. 2013 Sep 15;191(6):3410-8. doi: 10.4049/jimmunol.1301257. Epub 2013 Aug 9.
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The multiple shark Ig H chain genes rearrange and hypermutate autonomously.多种鲨鱼免疫球蛋白重链基因可自主发生重排和超突变。
J Immunol. 2011 Sep 1;187(5):2492-501. doi: 10.4049/jimmunol.1101671. Epub 2011 Jul 29.
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A shark antibody heavy chain encoded by a nonsomatically rearranged VDJ is preferentially expressed in early development and is convergent with mammalian IgG.由非体细胞重排的VDJ编码的鲨鱼抗体重链在早期发育中优先表达，并且与哺乳动物IgG趋同。
Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1775-80. doi: 10.1073/pnas.98.4.1775.
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Somatic variation precedes extensive diversification of germline sequences and combinatorial joining in the evolution of immunoglobulin heavy chain diversity.在免疫球蛋白重链多样性的进化过程中，体细胞变异先于种系序列的广泛多样化和组合连接。
J Exp Med. 1993 Sep 1;178(3):815-24. doi: 10.1084/jem.178.3.815.
8
T-cell receptor gene homologs are present in the most primitive jawed vertebrates.T细胞受体基因同源物存在于最原始的有颌脊椎动物中。
Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9248-52. doi: 10.1073/pnas.91.20.9248.
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Identification and characterization of T-cell antigen receptor-related genes in phylogenetically diverse vertebrate species.系统发育上不同脊椎动物物种中T细胞抗原受体相关基因的鉴定与表征
Immunogenetics. 1995;42(3):204-12. doi: 10.1007/BF00191226.
10
Diverse organization of immunoglobulin VH gene loci in a primitive vertebrate.一种原始脊椎动物中免疫球蛋白VH基因座的多样化组织
EMBO J. 1988 Nov;7(11):3413-22. doi: 10.1002/j.1460-2075.1988.tb03215.x.
Cell. 1980 Jun;20(2):313-9. doi: 10.1016/0092-8674(80)90617-0.
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Restricted association of V and J-C gene segments for mouse lambda chains.小鼠λ链V和J-C基因片段的限制性组合
Proc Natl Acad Sci U S A. 1984 Apr;81(8):2484-8. doi: 10.1073/pnas.81.8.2484.
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Somatic generation of antibody diversity.抗体多样性的体细胞产生。
Nature. 1983 Apr 14;302(5909):575-81. doi: 10.1038/302575a0.
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Multiple components in restriction enzyme digests of mammalian (insectivore), avian and reptilian genomic DNA hybridize with murine immunoglobulin VH probes.哺乳动物（食虫目）、鸟类和爬行类基因组DNA的限制性酶切消化产物中的多个组分与小鼠免疫球蛋白VH探针杂交。
Nucleic Acids Res. 1982 Jun 11;10(11):3371-80. doi: 10.1093/nar/10.11.3371.
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Physical linkage of the constant region genes for immunoglobulins lambda I and lambda III.免疫球蛋白λI和λIII恒定区基因的物理连锁。
Proc Natl Acad Sci U S A. 1981 Jun;78(6):3829-33. doi: 10.1073/pnas.78.6.3829.
8
Complete nucleotide sequence of mouse immunoglobulin mu gene and comparison with other immunoglobulin heavy chain genes.小鼠免疫球蛋白μ基因的完整核苷酸序列及其与其他免疫球蛋白重链基因的比较。
Nucleic Acids Res. 1980 Sep 11;8(17):3933-45. doi: 10.1093/nar/8.17.3933.
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Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines.前B细胞系中最靠近连接区（JH）的重链可变区（VH）基因片段的优先利用。
Nature. 1984;311(5988):727-33. doi: 10.1038/311727a0.
10
[The primary structure of a monoclonal IgM-immunoglobulin (macroglobulin Gal.), II: the amino acid sequence of the H-chain (mu-type), subgroup H III. Architecture of the complete IgM-molecule (author's transl)].[单克隆IgM免疫球蛋白（巨球蛋白Gal.）的一级结构，II：重链（μ型）的氨基酸序列，H III亚组。完整IgM分子的结构（作者译）]
Hoppe Seylers Z Physiol Chem. 1973 Oct-Nov;354(10-11):1505-9.