The SPANX gene family of cancer/testis-specific antigens:: Rapid evolution and amplification in African great apes and hominids
The SPANX gene family of cancer/testis-specific antigens:: Rapid evolution and amplification in African great apes and hominids
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DOI：
10.1073/pnas.0308532100
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发表时间：
2004-03-02
影响因子：
11.1
通讯作者：
Larionov, V
中科院分区：
文献类型：
--
作者：
Kouprina, N;Mullokandov, M;Larionov, V
与 X 染色体上的细胞核相关的人类精子蛋白 (SPANX) 基因包含一个具有五个已知成员（SPANX-A1、-A2、-B、-C 和 -D）的基因家族，编码癌症/睾丸特异性抗原，这些抗原是癌症免疫治疗的潜在靶标。这些高度相似的旁系同源基因聚集在 X 染色体上的 Xq27 处。我们分离并测序了与人类 SPANX 同源的灵长类基因组克隆。对这些克隆的分析和人类基因组序列的搜索揭示了一组未表征的基因 SPANX-N，该基因存在于所有灵长类动物以及小鼠和大鼠中。在人类中，四个 SPANX-N 基因在 Xq27 处包含一系列串联重复；该亚家族的第五个成员位于 Xp11。与 SPANX-A/D 类似，人类 SPANX-N 基因在正常睾丸和一些黑色素瘤细胞系中表达； SPANX 的睾丸特异性表达在小鼠中也是保守的。对内含子长短形式的分类分布的分析表明，SPANX-N是祖先形式，SPANX-A/D亚科是在人科动物谱系的共同祖先中进化而来的。引人注目的是，SPANX 基因的编码序列的进化速度比内含子和 5' 非翻译区快得多。同义和非同义密码子位置的进化速率之间存在很强的相关性，与非编码序列相比，这两者都加速了两倍或更多。因此，SPANX 家族的进化似乎涉及正向选择，它不仅影响蛋白质序列，还影响编码序列中的同义位点。
Human sperm protein associated with the nucleus on the X chromosome (SPANX) genes comprise a gene family with five known members (SPANX-A1, -A2, -B, -C and -D), encoding cancer/testis-specific antigens that are potential targets for cancer immunotherapy. These highly similar paralogous genes cluster on the X chromosome at Xq27. We isolated and sequenced primate genomic clones homologous to human SPANX Analysis of these clones and search of the human genome sequence revealed an uncharacterized group of genes, SPANX-N, which are present in all primates as well as in mouse and rat. In humans, four SPANX-N genes comprise a series of tandem duplicates at Xq27; a fifth member of this subfamily is located at Xp11. Similarly to SPANX-A/D, human SPANX-N genes are expressed in normal testis and some melanoma cell lines; testis-specific expression of SPANX is also conserved in mouse. Analysis of the taxonomic distribution of the long and short forms of the intron indicates that SPANX-N is the ancestral form, from which the SPANX-A/D subfamily evolved in the common ancestor of the hominoid lineage. Strikingly, the coding sequences of the SPANX genes evolved much faster than the intron and the 5' untranslated region. There is a strong correlation between the rates of evolution of synonymous and nonsynonymous codon positions, both of which are accelerated 2-fold or more compared to the noncoding sequences. Thus, evolution of the SPANX family appears to have involved positive selection that affected not only the protein sequence but also the synonymous sites in the coding sequence.