NKp30 (NCR3) is a pseudogene in 12 inbred and wild mouse strains, but an expressed gene in Mus caroli
NKp30 (NCR3) is a pseudogene in 12 inbred and wild mouse strains, but an expressed gene in Mus caroli
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DOI：
10.1093/molbev/msi162
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发表时间：
2005-08-01
影响因子：
10.7
通讯作者：
Aguado, B
中科院分区：
文献类型：
--
作者：
Hollyoake, M;Campbell, RD;Aguado, B
蛋白质编码片段的古老复制和重排导致了复杂的基因家族关系。因此，基因产物可能获得新的特异性，改变识别特性，改变功能，甚至丧失功能。天然细胞毒性受体（NCR）家族是天然杀伤（NK）激活受体，其成员是NKp46（NCR 1）、NKp44（NCR 2）和NKp30（NCR 3）。NCR蛋白是假定的免疫球蛋白超家族成员，其配体未知。NKp46基因在人和小鼠中存在并表达，NKp44仅在人中存在并表达，NKp30在人中存在并表达，但在小鼠中是不表达的假基因。通过搜索数据库，我们检测到三个NCR成员的可变剪接形式。此外，我们已经表明，通过逆转录-聚合酶链反应（RT-PCR）分析，人NKp30基因在组织中呈现差异表达模式。然而，没有检测到小鼠NKp30的表达序列标签（EST），基因组序列包含两个提前终止密码子，这将编码一个严重截短的无功能蛋白。我们对13个小鼠近交系和野生品系的基因组DNA进行了测序，发现NKp30在除卡罗利小鼠外的所有小鼠品系中都是假基因，卡罗利小鼠的两个单核苷酸多态性（SNP）消除了过早终止密码子。我们观察到，实验室近交系的外显子序列，遗传相同，除了小鼠m。C3H肌小家鼠品系仅具有少数SNP，但其余品系逐渐积累了多个SNP，主要集中在功能性免疫球蛋白和细胞内结构域。对M. caroli组织样品鉴定了两种转录物，其中一种将编码推定的可溶性NKp30蛋白，也在大鼠中检测到，但在人中未检测到。我们已经观察到NKp30（和NKp46）的细胞内结构域在不同物种中不保守，当比较人与小鼠和大鼠时，具有最显著的差异。NKp44基因仅在人类中发现，并且在其"茎"和细胞内结构域中显示三种不同的剪接形式。搜索NKp44直系同源物，我们发现与来自一种新的啮齿动物TREM家族成员的EST相似，我们称之为TREM6，而不是任何可能的NKp44直系同源物。
Ancient duplications and rearrangements of protein-coding segments have resulted in complex gene family relationships. As a result, gene products may acquire new specificities, altered recognition properties, modified functions, and even loss of functionality. The natural cytotoxicity receptor (NCR) family are natural killer (NK)-activating receptors whose members are NKp46 (NCRl), NKp44 (NCR2), and NKp30 (NCR3). The NCR proteins are putative immunoglobulin superfamily members whose ligands are unknown. The NKp46 gene is present and expressed in human and mouse, NKp44 is only present and expressed in human, and NKp30 is present and expressed in human but is a nonexpressed pseudogene in mouse. By searching databases we have detected alternatively spliced forms of the three NCR members. In addition, we have shown by reverse transcription-polymerase chain reaction (RT-PCR) analysis that the human NKp30 gene presents differential expression patterns in tissues. However, no expressed sequence tags (ESTs) are detected for mouse NKp30, and the genomic sequence contains two premature stop codons, which would encode a severely truncated nonfunctional protein. We have sequenced genomic DNA from 13 mouse inbred and wild strains and discovered that NKp30 is a pseudogene in every mouse strain sequenced except Mus caroli where two single nucleotide polymorphisms (SNPs) abolished the premature stop codons. We observed that the laboratory-inbred strains are, for the exonic sequences, genetically identical, except Mus m. musculus C3H. The Mus musculits strains only have a few SNPs, but the rest of the Mus strains have accumulated gradually several SNPs, mainly in the functional immunoglobulin and intracellular domains. RT-PCR analysis performed on RNA from M. caroli tissue samples identified two transcripts, one of which would encode a putative soluble NKp30 protein, also detected in rat but not in human. We have observed that the intracellular domains of NKp30 (and NKp46) are not conserved among the different species, with the most striking difference when comparing human against mouse and rat. The NKp44 gene is only found in human and shows three different splice forms varying in their "stalk" and intracellular domains. Searching for NKp44 orthologs, we found similarity to ESTs from a novel rodent TREM family member, which we termed TREM6, and not to any possible NKp44 ortholog.