Hayman J R, Ghaffari S H, Lobb C J
Department of Microbiology, University of Mississippi Medical Center, Jackson 39216-4505.
J Immunol. 1993 Oct 1;151(7):3587-96.
The JH locus of the channel catfish has been characterized to determine the organization and structural diversity of JH segments. These analyses indicate that there are a total of nine JH segments tightly clustered within a region spanning about 2.2 kb. The JH locus is closely linked to the CH 1 domain of the expressed catfish H chain; the distance between the CH proximal JH segment (JH9) and the CH 1 domain is about 1.8 kb. Each JH segment has an upstream recombination sequence, which includes a T-rich nonamer, a 22- to 24-bp spacer, and a phylogenetically conserved heptamer. Each JH segment also has an open reading frame that encodes the conserved framework region 4 tryptophan (Trp-103) and terminates with a RNA donor splice site. The catfish JH locus contains an internal repetitive sequence region characterized by a short (183-188 bp) repeat that occurs sequentially five times. Strong sequence homology as well as the unified length of the repeated sequences indicate that JH segments JH3-JH7 probably arose as the result of a series of homologous but unequal crossover events. Sequence alignments of the duplicated JH segments indicates that there is diversity within the 5-11 nucleotides located immediately downstream from the heptamer, an observation which indicates that closely related JH segments can serve to enhance CDR3 diversity in the expressed H chain. Comparisons of the genomic JH sequences with different cDNA clones indicate that each JH segment is probably functional and that junctional diversity serves an important role in the generation of CDR3 diversity. In addition, single base differences observed in comparisons of JH-encoded regions indicate that there is probably somatic mutation or allelic variation of genomic JH segments. These studies suggest that the characteristic structure and organizational pattern of JH segments in higher vertebrates may have evolved early in vertebrate phylogeny at the level of the bony fish.
对斑点叉尾鮰的JH基因座进行了表征，以确定JH区段的组织和结构多样性。这些分析表明，共有9个JH区段紧密聚集在一个跨度约2.2 kb的区域内。JH基因座与表达的鮰鱼重链的CH 1结构域紧密相连；CH近端JH区段（JH9）与CH 1结构域之间的距离约为1.8 kb。每个JH区段都有一个上游重组序列，其中包括一个富含T的九聚体、一个22至24 bp的间隔区和一个系统发育保守的七聚体。每个JH区段还有一个开放阅读框，其编码保守的构架区4色氨酸（Trp-103），并以RNA供体剪接位点终止。鮰鱼JH基因座包含一个内部重复序列区域，其特征是一个短（183 - 188 bp）重复序列连续出现五次。强烈的序列同源性以及重复序列的统一长度表明，JH区段JH3 - JH7可能是一系列同源但不等交换事件的结果。重复JH区段的序列比对表明，在七聚体下游紧邻的5 - 11个核苷酸内存在多样性，这一观察结果表明，密切相关的JH区段可用于增强表达的重链中CDR3的多样性。基因组JH序列与不同cDNA克隆的比较表明，每个JH区段可能都具有功能，并且连接多样性在CDR3多样性的产生中起重要作用。此外，在JH编码区比较中观察到的单碱基差异表明，基因组JH区段可能存在体细胞突变或等位基因变异。这些研究表明，高等脊椎动物中JH区段的特征结构和组织模式可能在脊椎动物系统发育早期，即在硬骨鱼水平就已经进化形成。
