Loflin P T, Laud P R, Watkins D I, Lawlor D A
Department of Immunology, Box 180, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Immunogenetics. 1996;44(3):161-9. doi: 10.1007/BF02602581.
Transporters associated with antigen processing molecules (TAP1 and TAP2) mediate the transfer of cytosolic peptides into the lumen of the endoplasmic reticulum for association with newly synthesized class I molecules of the major histocompatibility complex. Previous molecular and functional analyses of rat and human TAP2 homologues indicated major differences in gene diversification patterns and selectivity of peptides transported. Therefore, in this study, we analyzed the alleles of the gorilla TAP2 locus to determine whether the pattern of diversification resembled that in either of those two species. Sequence analysis of the TAP2 cDNAs from gorilla Epstein-Barr virus-transformed B-cell lines revealed four alleles with a genetic distance of less than 1%. The nucleotide substitutions distinguishing the alleles are confined to the 3' half of the coding region and occur individually or within two small clusters of variability. Diversification of the locus appears to have resulted from point substitutions and recombinational events. Evolutionary-rate estimates for the TAP2 gene in gorilla and human closely approximate those observed for other hominoid genes. The amino acid polymorphisms within the gorilla molecules are distinct from those in the human homologues. The absence of ancestral polymorphisms suggests that gorilla and human TAP2 genes have not evolved in a trans-species fashion but rather have diversified since the divergence of the lineages.
与抗原加工分子相关的转运体（TAP1和TAP2）介导胞质肽转运至内质网腔，以便与新合成的主要组织相容性复合体I类分子结合。先前对大鼠和人类TAP2同源物的分子及功能分析表明，在基因多样化模式和所转运肽的选择性方面存在重大差异。因此，在本研究中，我们分析了大猩猩TAP2基因座的等位基因，以确定其多样化模式是否与这两个物种中的任何一个相似。对来自大猩猩爱泼斯坦-巴尔病毒转化的B细胞系的TAP2 cDNA进行序列分析，发现了四个遗传距离小于1%的等位基因。区分这些等位基因的核苷酸替换局限于编码区的3'端，且单独发生或出现在两个小的可变簇内。该基因座的多样化似乎是由点替换和重组事件导致的。大猩猩和人类TAP2基因的进化速率估计与在其他类人猿基因中观察到的情况非常接近。大猩猩分子中的氨基酸多态性与人类同源物中的不同。缺乏祖先多态性表明，大猩猩和人类的TAP2基因并非以跨物种方式进化，而是自谱系分化以来已经多样化。
