MOLECULAR STUDY OF ALLORECOGNITION IN A PROTOCHORDATE

描述原脊索动物，Botryllus schlosseri，经历了一种遗传定义的自然移植反应，两个生长中的菌落边缘相互作用。这种同种异体识别现象类似于在高等脊椎动物中的造血抗性（Hh）：它主要由具有多个共显性表达等位基因（称为Fu/HC）的单个基因座控制;并且它可能是防止排斥反应的自我识别。原脊索动物是所有脊索动物的系统发育祖先，因此基于Fu/HC的同种异体识别系统可能是祖先MHC，也可能是脊椎动物中尚未发现的新的同种异体识别系统。然而，Fu/HC基因座从未在分子水平上表征。使用我们实验室开发的Fu/HC定义的葡萄球菌近交系，我们正在采取基因组方法来分离和分析该基因座，方法是绘制遗传图谱，分离紧密连锁的侧翼标记，并使用这些标记来定位克隆Fu/HC基因座。候选基因将与功能组织相容性相关，并将表征相应的多肽。

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.