Terado Tokio, Okamura Kazuhiko, Ohta Yuko, Shin Dong-Ho, Smith Sylvia L, Hashimoto Keiichiro, Takemoto Tadashi, Nonaka Mayumi I, Kimura Hiroshi, Flajnik Martin F, Nonaka Masaru
Department of Experimental Radiology, Shiga University of Medical Science, Ohtsu-shi, Shiga, Japan.
J Immunol. 2003 Sep 1;171(5):2461-6. doi: 10.4049/jimmunol.171.5.2461.
To clarify the evolutionary origin of the linkage of the MHC class III complement genes with the MHC class I and II genes, we isolated C4 cDNA from the banded hound shark (Triakis scyllium). Upon phylogenetic tree analysis, shark C4 formed a well-supported cluster with C4 of higher vertebrates, indicating that the C3/C4 gene duplication predated the divergence of cartilaginous fish from the main line of vertebrate evolution. The deduced amino acid sequence predicted the typical C4 three-subunits chain structure, but without the histidine residue catalytic for the thioester bond, suggesting the human C4A-like specificity. The linkage analysis of the complement genes, one C4 and two factor B (Bf) genes, to the shark MHC was performed using 56 siblings from two typing panels of T. scyllium and Ginglymostoma cirratum. The C4 and one of two Bf genes showed a perfect cosegregation with the class I and II genes, whereas two recombinants were identified for the other Bf gene. These results indicate that the linkage between the complement C4 and Bf genes, as well as the linkage between these complement genes and the MHC class I and II genes were established before the emergence of cartilaginous fish >460 million years ago.
为了阐明MHC III类补体基因与MHC I类和II类基因连锁的进化起源，我们从带状星鲨（Triakis scyllium）中分离出C4 cDNA。经过系统发育树分析，鲨鱼C4与高等脊椎动物的C4形成了一个得到充分支持的聚类，表明C3/C4基因复制早于软骨鱼从脊椎动物进化主线中分化出来的时间。推导的氨基酸序列预测了典型的C4三聚体链结构，但没有硫酯键催化所需的组氨酸残基，提示具有人类C4A样特异性。利用来自星鲨和皱唇鲨两个分型组的56个同胞对补体基因（一个C4基因和两个B因子（Bf）基因）与鲨鱼MHC进行连锁分析。C4基因和两个Bf基因中的一个与I类和II类基因表现出完全共分离，而另一个Bf基因鉴定出两个重组体。这些结果表明，补体C4和Bf基因之间的连锁，以及这些补体基因与MHC I类和II类基因之间的连锁在4.6亿多年前软骨鱼出现之前就已建立。
