Repeated recruitment of LTR retrotransposons as promoters by the anti-apoptotic locus NAIP during mammalian evolution.
Repeated recruitment of LTR retrotransposons as promoters by the anti-apoptotic locus NAIP during mammalian evolution.
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DOI：
10.1371/journal.pgen.0030010
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发表时间：
2007-01-12
期刊：
影响因子：
4.5
通讯作者：
Mager DL
中科院分区：
文献类型：
--
作者：
Romanish MT;Lock WM;van de Lagemaat LN;Dunn CA;Mager DL
神经元凋亡抑制蛋白（NAIP，也称为BIRC 1）是保守的凋亡抑制蛋白（IAP）家族的成员。该基因座的谱系特异性重排和扩增在灵长类动物和啮齿类动物中产生了不同的拷贝数，人类保留了单个功能拷贝，而小鼠拥有多个拷贝，这取决于菌株。该基因在疾病中的作用已被记录，但对NAIP的转录调控知之甚少。我们在这里表明，NAIP有多个启动子共享人类和啮齿动物之间没有相似性。此外，我们证明，多个，驯化的长末端重复序列（LTRs）的内源性逆转录病毒元件提供NAIP启动子在人类，小鼠和大鼠的功能。在人类中，LTR充当组织特异性启动子，主要在睾丸中有活性。然而，在啮齿动物中，我们的证据表明，所有啮齿动物基因共同的祖先LTR是这些基因的主要组成型启动子，并且在两个小鼠基因中发现的第二个LTR是次要启动子。因此，独立获得的LTRs承担了调节作用的orthopathic基因，一个显着的进化情景。我们还证明，IAP家族基因的5′侧翼区作为一个群体，在人类和小鼠中富集LTR插入相比，平均基因。我们对这些发现提出了几种可能的解释，包括一种假设，即NAIP或其他IAP基因附近的LTR的募集可能代表了宿主细胞调节凋亡反应的适应。当逆转录病毒感染细胞时，病毒DNA插入细胞基因组。如果这种情况发生在配子（卵子或精子）中，病毒DNA将从父母传给后代，就像所有染色体DNA一样。在进化过程中，这种配子感染非常普遍，以至于现在正常人类和小鼠基因组的8%-10%由古老的病毒DNA组成，称为内源性逆转录病毒（ERV）。在人类中，这些ERV是突变的或“死亡的”，但是已经显示ERV调节区可以被宿主用来帮助控制细胞基因的表达。在这里，我们报告了这种现象的一个显著例子。我们证明了人类和啮齿动物的神经元凋亡抑制蛋白（NAIP）基因，参与防止细胞死亡，使用不同的ERV序列来驱动基因表达。此外，在灵长类动物和啮齿类动物谱系中，两个独立的ERV有助于NAIP基因表达。在整个进化过程中，NAIP基因对ERV的重复招募不太可能是偶然发生的。我们提供了一些潜在的解释，包括有趣的可能性，它可能是有利的抗细胞死亡基因，如NAIP使用ERVs来控制它们的表达。这些结果支持了这样一种观点，即并非我们基因组中所有的逆转录病毒残留物都只是垃圾DNA。
Neuronal apoptosis inhibitory protein (NAIP, also known as BIRC1) is a member of the conserved inhibitor of apoptosis protein (IAP) family. Lineage-specific rearrangements and expansions of this locus have yielded different copy numbers among primates and rodents, with human retaining a single functional copy and mouse possessing several copies, depending on the strain. Roles for this gene in disease have been documented, but little is known about transcriptional regulation of NAIP. We show here that NAIP has multiple promoters sharing no similarity between human and rodents. Moreover, we demonstrate that multiple, domesticated long terminal repeats (LTRs) of endogenous retroviral elements provide NAIP promoter function in human, mouse, and rat. In human, an LTR serves as a tissue-specific promoter, active primarily in testis. However, in rodents, our evidence indicates that an ancestral LTR common to all rodent genes is the major, constitutive promoter for these genes, and that a second LTR found in two of the mouse genes is a minor promoter. Thus, independently acquired LTRs have assumed regulatory roles for orthologous genes, a remarkable evolutionary scenario. We also demonstrate that 5′ flanking regions of IAP family genes as a group, in both human and mouse are enriched for LTR insertions compared to average genes. We propose several potential explanations for these findings, including a hypothesis that recruitment of LTRs near NAIP or other IAP genes may represent a host-cell adaptation to modulate apoptotic responses. When retroviruses infect cells, the viral DNA inserts into the cellular genome. If this happens in gametes (egg or sperm), the viral DNA will be transmitted from parent to offspring, like all chromosomal DNA. Through evolutionary time, such infections of gametes have been so prevalent that 8%–10% of the normal human and mouse genomes are now composed of ancient viral DNA, termed endogenous retroviruses (ERVs). In human, these ERVs are mutated or “dead” but it has been shown that ERV regulatory regions can be employed by the host to help control expression of cellular genes. Here, we report on a remarkable example of this phenomenon. We demonstrate that both the human and rodent neuronal apoptosis inhibitory protein (NAIP) genes, involved in preventing cell death, use different ERV sequences to drive gene expression. Moreover, in each of the primate and rodent lineages, two separate ERVs contribute to NAIP gene expression. This repeated ERV recruitment by NAIP genes throughout evolution is very unlikely to have occurred by chance. We offer a number of potential explanations, including the intriguing possibility that it may be advantageous for anti-cell death genes like NAIP to use ERVs to control their expression. These results support the view that not all retroviral remnants in our genome are simply junk DNA.
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影响因子：
1.5
作者：
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通讯作者：
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影响因子：
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作者：
Jurka, J;Kapitonov, VV;Walichiewicz, J
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影响因子：
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作者：
Frith, Martin C.;Ponjavic, Jasmina;Sandelin, Albin
通讯作者：
Sandelin, Albin
DOI：
10.1073/pnas.73.2.646
发表时间：
1976-01-01
影响因子：
11.1
作者：
HAMPAR, B;AARONSON, SA;DUNN, CY
通讯作者：
DUNN, CY