A novel testis ubiquitin-binding protein gene arose by exon shuffling in hominoids
A novel testis ubiquitin-binding protein gene arose by exon shuffling in hominoids
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DOI：
10.1101/gr.6252107
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发表时间：
2007-08-01
期刊：
影响因子：
7
通讯作者：
Kazazian, Haig H., Jr.
中科院分区：
文献类型：
--
作者：
Babushok, Daria V.;Ohshima, Kazuhiko;Kazazian, Haig H., Jr.
大多数新基因是由现有基因结构的复制产生的，在此之后，对新拷贝的宽松选择经常导致副本的突变失活；只有在极少数情况下才会出现功能被修改的新基因。在这里，我们描述了一种独特的基因创造机制，即在RNA水平上从不同的基因组装新的功能域组合，然后产生的嵌合体被L1反转录转座子逆转录并整合到基因组中。我们鉴定了一个新的基因，我们将其命名为PIP5K1A和PSMD4样（PIPSL），通过这种机制在类人猿祖先的磷脂酰肌醇-4-磷酸5激酶（PIP5K1A）和26S蛋白酶体亚基（PSMD4）基因之间的基因间转录产生。PIPSL在人类和黑猩猩的睾丸中都有特异性转录，并且在这些灵长类谱系中通过独立的机制被转录后抑制。PIPSL基因编码一个结合PIP5K1A脂质激酶结构域和PSMD4泛素结合基序的嵌合蛋白。对PIPSL的强阳性选择导致其与亲本基因PIP5K1A和PSMD4迅速分化，形成一个嵌合蛋白，具有明显的细胞定位和最低的脂激酶活性，但与细胞泛素化蛋白有显著的亲和力。PIPSL是一种受到严格调控的睾丸特异性泛素结合蛋白，在类人猿中由一种不寻常的外显子改组机制形成，是睾丸特异性基因快速进化的一个关键例子。
Most new genes arise by duplication of existing gene structures, after which relaxed selection on the new copy frequently leads to mutational inactivation of the duplicate; only rarely will a new gene with modified function emerge. Here we describe a unique mechanism of gene creation, whereby new combinations of functional domains are assembled at the RNA level from distinct genes, and the resulting chimera is then reverse transcribed and integrated into the genome by the L1 retrotransposon. We characterized a novel gene, which we termed PIP5K1A and PSMD4-like (PIPSL), created by this mechanism from an intergenic transcript between the phosphatidylinositol-4-phosphate 5-kinase (PIP5K1A) and the 26S proteasome subunit (PSMD4) genes in a hominoid ancestor. PIPSL is transcribed specifically in the testis both in humans and chimpanzees, and is post-transcriptionally repressed by independent mechanisms in these primate lineages. The PIPSL gene encodes a chimeric protein combining the lipid kinase domain of PIP5K1A and the ubiquitin-binding motifs of PSMD4. Strong positive selection on PIPSL led to its rapid divergence from the parental genes PIP5K1A and PSMD4, forming a chimeric protein with a distinct cellular localization and minimal lipid kinase activity, but significant affinity for cellular ubiquitinated proteins. PIPSL is a tightly regulated, testis-specific novel ubiquitin-binding protein formed by an unusual exon-shuffling mechanism in hominoid primates and represents a key example of rapid evolution of a testis-specific gene.