Homologs of Drosophila P transposons were mobile in zebrafish but have been domesticated in a common ancestor of chicken and human
Homologs of Drosophila P transposons were mobile in zebrafish but have been domesticated in a common ancestor of chicken and human
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DOI：
10.1093/molbev/msi068
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发表时间：
2005-04-01
影响因子：
10.7
通讯作者：
Hagemann, S
中科院分区：
文献类型：
--
作者：
Hammer, SE;Strehl, S;Hagemann, S
脊椎动物和无脊椎动物基因组的很大一部分是由可移动元件及其衍生物组成的。果蝇的P元件是研究最深入的转座子家族之一，被认为只存在于双翅目昆虫的基因组中。基于人类基因组计划提供的数据，2001年，我们小组在人类基因组中鉴定了一个P元件同源序列。这个P元件同源的人类基因命名为phsa，全长19533个核苷酸，由6个外显子和5个内含子组成，编码一个功能未知的蛋白质，长度为903个氨基酸。推测的PHSA蛋白的N端TAP结构域与果蝇P元件转座酶的位点特异性DNA结合域相似。在本研究中，FISH分析和对人lambda基因组文库的筛选发现，PHSA的单拷贝位于4号染色体的长安上，位于假想蛋白质DKFZp686L1814编码基因的上游。在鸡基因组中发现同源基因PggA的基因排列相同，因此在4号染色体长臂上的同源位置显示PggA。单拷贝的基因状态以及没有末端反向重复和靶点重复表明PHSA和PggA构成了驯化的静止序列。相反，在斑马鱼中可以鉴定出相当数量的具有末端反向重复序列和完整靶点复制的P-同源序列，这有力地表明Pdre元件在斑马鱼基因组中是可移动的。PDRE元件是在脊椎动物中发现的第一个类似P的转座子。关于PHSA，基因表达研究表明，PHSA在广泛的人体组织中表达，这表明推测的PHSA蛋白在特定的代谢途径中发挥着尚未被了解但必不可少的作用。我们证明，P-同源DNA序列存在于21种被分析的脊椎动物的基因组中，但仅作为啮齿类动物的雏形。最后，在“分子驯化”假说与“源基因假说”的背景下讨论了P元素同源脊椎动物序列的进化史。
A substantial fraction of vertebrate and invertebrate genomes is composed of mobile elements and their derivatives. One of the most intensively studied transposon families, the P elements of Drosophila, was thought to exist exclusively in the genomes of dipteran insects. Based on the data provided by the human genome project, in 2001 our group has identified a P element-homologous sequence in the human genome. This P element-homologous human gene, named Phsa, is 19,533 nucleotides long, comprises six exons and five introns, and encodes a protein of still unknown function with a length of 903 amino acid residues. The N-terminal THAP domain of the putative Phsa protein shows similarities to the site-specific DNA-binding domain of the Drosophila P element transposase. In the present study, FISH analysis and the screening of a human lambda genomic library revealed a single copy of Phsa located on the long ann of chromosome 4, upstream of a gene coding for the hypothetical protein DKFZp686L1814. The same gene arrangement was found for the homologous gene Pgga in the genome of chicken, thus, displaying Pgga at orthologous position on the long arm of chromosome 4. The single-copy gene status and the absence of terminal inverted repeats and target-site duplications indicate that Phsa and Pgga constitute domesticated stationary sequences. In contrast, a considerable number of P-homologous sequences with terminal inverted repeats and intact target-site duplications could be identified in zebrafish, strongly indicating that Pdre elements were mobile within the zebrafish genome. Pdre elements are the first P-like transposons identified in a vertebrate species. With respect to Phsa, gene expression studies showed that Phsa is expressed in a broad range of human tissues, suggesting that the putative Phsa protein plays a not yet understood but essential role in a specific metabolic pathway. We demonstrate that P-homologous DNA sequences occur in the genomes of 21 analyzed vertebrates but only as rudiments in the rodents. Finally, the evolutionary history of P element-homologous vertebrate sequences is discussed in the context of the "molecular domestication" hypothesis versus the "source gene hypothesis."