MOLECULAR STUDY OF ALLORECOGNITION IN A PROTOCHORDATE

描述原脊索动物，Botryllus schlosseri，经历了遗传上确定的自然移植反应，两个生长菌落的边缘相互作用。这种同种异体识别现象类似于高等脊椎动物的造血抗性（Hh）：它主要由单个基因座和多个共显性表达的等位基因（称为Fu/HC）控制；很可能是对自我的认识阻止了拒绝反应。原脊索动物是所有脊索动物的祖先，因此基于Fu/ hc的同种异体识别系统可能是祖先的MHC，也可能是一种在脊椎动物中尚未发现的新型同种异体识别系统。然而，Fu/HC位点从未在分子水平上进行过表征。利用我们实验室开发的Fu/HC定义的Botryllus自交系，我们采用基因组方法分离和分析该基因座，方法是制作遗传图谱，分离出紧密连接的侧翼标记，并利用这些标记对Fu/HC基因座进行定位克隆。候选基因将与功能组织相容性相关，相应的多肽将被表征。

DESCRIPTION The protochordate, Botryllus schlosseri, undergoes a genetically defined, natural transplantation reaction the edges of two growing colonies interact. This allorecognition phenomena is analogous to that seen in hematopoietic resistance (Hh) in the higher vertebrates: it is principally controlled by a single locus with multiple co-dominantly expressed alleles (called the Fu/HC); and it is likely the recognition of self which prevents a rejection reaction. Protochordates are phylogenetic predecessors to all chordates, thus the Fu/HC-based allorecognition system may either be the ancestral MHC, or possibly a novel allorecognition system still undiscovered in the vertebrates. However, the Fu/HC locus has never been characterized at the molecular level. Using Fu/HC defined, inbred strains of Botryllus developed in our lab, we are taking a genomic approach to isolate and analyze this locus by making a genetic map, isolating tightly-linked flanking markers, and using these to positionally clone the Fu/HC locus. Candidate genes will be correlated with functional histocompability and the corresponding polypeptides will be characterized.