Yuhki N, Heidecker G F, O'Brien S J
Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, MD 21701-1013.
J Immunol. 1989 May 15;142(10):3676-82.
The abundant functional polymorphism and evolutionary divergence of mammalian MHC class I genes has been affirmed recently by sequence analysis of more than 40 mouse H-2 and human HLA transcripts. In a comparative approach to the evolution of the MHC, we isolated eight molecular clones of feline MHC (termed FLA for feline leukocyte antigen) class I genes from a cDNA library of a cat T cell lymphoma line. DNA sequence analysis of eight clones revealed that they all fell into one of two internally identical allelic groups which differed by 9% of their nucleotide sequences. The occurrence of only two allelic cDNA clones is consistent with the expression of a single heterozygous functional class I gene in the studied cell line despite the occurrence of more than 20 class I copies estimated to be present in the cat genome. Comparison of the FLA class I coding sequence with other class I genes from other species revealed that the domestic cat genes display 81 to 82% sequence identity with human, and 73 to 79% sequence identity with mouse class I genes. Feline and human class I genes have similar sequences and protein structures, with three (alpha) extracellular domains, one transmembrane domain, and one cytoplasmic domain. Variable codons detected in FLA class I alleles were, in most cases, in positions which were also variable in humans and mice, whereas invariant positions with defined functional constraints were generally conserved and invariant between the three species as well. Southern analysis of DNA from diverse species of Felidae revealed a similar numerosity and restriction pattern indicating conservation of the organization of class I genes during the Felidae radiation.
最近，通过对40多种小鼠H-2和人类HLA转录本的序列分析，证实了哺乳动物MHC I类基因丰富的功能多态性和进化差异。在对MHC进化的比较研究中，我们从猫T细胞淋巴瘤系的cDNA文库中分离出8个猫MHC（称为猫白细胞抗原FLA）I类基因的分子克隆。对8个克隆的DNA序列分析表明，它们都属于两个内部相同的等位基因组之一，这两个组的核苷酸序列有9%的差异。尽管估计猫基因组中存在20多个I类基因拷贝，但在所研究的细胞系中仅出现两个等位基因cDNA克隆，这与单个杂合功能性I类基因的表达是一致的。将FLA I类编码序列与其他物种的其他I类基因进行比较，发现家猫基因与人类基因的序列同一性为81%至82%，与小鼠I类基因的序列同一性为73%至79%。猫和人类的I类基因具有相似的序列和蛋白质结构，有三个（α）细胞外结构域、一个跨膜结构域和一个细胞质结构域。在FLA I类等位基因中检测到的可变密码子，在大多数情况下，其位置在人类和小鼠中也是可变的，而具有明确功能限制的不变位置在这三个物种之间通常也是保守和不变的。对不同猫科动物物种的DNA进行Southern分析，发现了相似的数量和限制性模式，表明在猫科动物辐射过程中I类基因的组织是保守的。
