Comparison of chimpanzee and human leukocyte Ig-like receptor genes reveals framework and rapidly evolving genes

Comparison of chimpanzee and human leukocyte Ig-like receptor genes reveals framework and rapidly evolving genes
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DOI:
10.4049/jimmunol.167.10.5786
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发表时间:
2001-11-15
影响因子:
4.4
通讯作者:
Parham, P
Parham, P
中科院分区:
医学2区
文献类型:
--
作者:
Canavez, F;Young, NT;Parham, P

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人类19号染色体上的白细胞受体复合物(LRC)含有相关的IG超家族杀伤细胞Ig样受体(KIR)和白细胞Ig样受体(LIR)基因。在此之前,我们发现人类和黑猩猩之间的KIR基因存在很大差异,估计灵长类物种的基因组序列相似性高达99.8%。在这里,共同的黑猩猩LIR基因的识别,表征,并与他们的人类同行进行比较。从筛选黑猩猩脾细胞cDNA文库中,分离对应于9种不同黑猩猩LIR的克隆并测序。对48只无关黑猩猩的基因组DNA分析显示,42只黑猩猩拥有所有9种LIR基因,6只黑猩猩只缺乏其中一种基因。在结构多样性和功能类型上,黑猩猩LIR涵盖了人类LIR的范围。虽然两个物种具有相同数量的抑制性LIR,但人类具有更多的激活受体,这也是KIR的趋势。四个黑猩猩LIR显然是人类LIR的直系同源物。其他五个黑猩猩LIR与人类LIR集群有旁系同源关系,并经历了多次重组。像人类基因一样,黑猩猩的LIR基因似乎被组织成两个重复的区块,每个区块包含两个正向同源基因。这种组织提供了一个保守的框架,其中有快速进化的基因簇。人类和黑猩猩的KIR基因有类似的排列。而AIR和LIR基因可以表现出更大的种间差异比基因组的平均值,在每个物种的LIR基因家族比KIR基因家族更保守。
The leukocyte receptor complex (LRC) on human chromosome 19 contains related Ig superfamily killer cell Ig-like receptor (KIR) and leukocyte Ig-like receptor (LIR) genes. Previously, we discovered much difference in the KIR genes between humans and chimpanzees, primate species estimated to have similar to 99.8% genomic sequence similarity. Here, the common chimpanzee LIR genes are identified, characterized, and compared with their human counterparts. From screening a chimpanzee splenocyte cDNA library, clones corresponding to nine different chimpanzee LIRs were isolated and sequenced. Analysis of genomic DNA from 48 unrelated chimpanzees showed 42 to have all nine LIR genes, and six animals to lack just one of the genes. In structural diversity and functional type, the chimpanzee LIRs cover the range of human LIRs. Although both species have the same number of inhibitory LIRs, humans have more activating receptors, a trend also seen for KIRs. Four chimpanzee LIRs are clearly orthologs of human LIRs. Five other chimpanzee LIRs have paralogous relationships with clusters of human LIRs and have undergone much recombination. Like the human genes, chimpanzee LIR genes appear to be organized into two duplicated blocks, each block containing two orthologous genes. This organization provides a conserved framework within which there are clusters of faster evolving genes. Human and chimpanzee KIR genes have an analogous arrangement. Whereas both AIR and LIR genes can exhibit greater interspecies differences than the genome average, within each species the LIR gene family is more conserved than the KIR gene family.