The artiodactyl APOBEC3 innate immune repertoire shows evidence for a multi-functional domain organization that existed in the ancestor of placental mammals.
The artiodactyl APOBEC3 innate immune repertoire shows evidence for a multi-functional domain organization that existed in the ancestor of placental mammals.
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DOI：
10.1186/1471-2199-9-104
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发表时间：
2008-11-18
影响因子：
--
通讯作者：
Harris RS
中科院分区：
文献类型：
--
作者：
LaRue RS;Jónsson SR;Silverstein KA;Lajoie M;Bertrand D;El-Mabrouk N;Hötzel I;Andrésdóttir V;Smith TP;Harris RS
APOBEC3(A3)蛋白使DNA胞嘧啶脱氨基，阻止逆转录病毒和逆转录转座子的复制。每个A3基因编码一个含有一个或两个保守的锌配位基序(Z1、Z2或Z3)的蛋白质。在小鼠(Z2-Z3)中存在一个A3基因，在人类中存在七个A3A-H基因(Z1a、Z2a-Z1b、Z2b、Z2c-Z2d、Z2e-Z2f、Z2g-Z1c、Z3)，这表明进化具有非凡的灵活性。为了深入了解A3基因扩展的机制和时机，以及这些基因的功能模块，我们分析了绵羊、牛和猪三个偶趾龙血统的A3全套基因的基因组序列、表达cDNA和活性。羊和牛有三个A3基因，A3Z1，A3Z2和A3Z3，而猪只有两个，A3Z2和A3Z3。家猪和野猪的比较表明，A3Z1在猪的谱系中缺失。在这三个物种中，通读转录和选择性剪接也产生了具有催化活性的双结构域A3Z2-Z3蛋白，具有明显的细胞质定位。因此，羊和牛的三个A3基因编码四个保守的活性蛋白。这些数据和系统发育分析一起表明，在偶蹄目和灵长类动物的共同祖先(即胎盘哺乳动物的祖先)中存在一个相似的、功能模块化的A3谱系。因此，这个哺乳动物的祖先拥有最小的A3基因组，Z1-Z2-Z3，需要通过一系列引人注目的8次重组事件进化成今天的11个Z结构域的人类谱系。哺乳动物A3基因的动态重组填充历史与该基因座的模块化性质以及其中大多数事件(特别是扩增)是由古代致病逆转录病毒感染选择的模型一致。
APOBEC3 (A3) proteins deaminate DNA cytosines and block the replication of retroviruses and retrotransposons. Each A3 gene encodes a protein with one or two conserved zinc-coordinating motifs (Z1, Z2 or Z3). The presence of one A3 gene in mice (Z2–Z3) and seven in humans, A3A-H (Z1a, Z2a-Z1b, Z2b, Z2c-Z2d, Z2e-Z2f, Z2g-Z1c, Z3), suggests extraordinary evolutionary flexibility. To gain insights into the mechanism and timing of A3 gene expansion and into the functional modularity of these genes, we analyzed the genomic sequences, expressed cDNAs and activities of the full A3 repertoire of three artiodactyl lineages: sheep, cattle and pigs. Sheep and cattle have three A3 genes, A3Z1, A3Z2 and A3Z3, whereas pigs only have two, A3Z2 and A3Z3. A comparison between domestic and wild pigs indicated that A3Z1 was deleted in the pig lineage. In all three species, read-through transcription and alternative splicing also produced a catalytically active double domain A3Z2-Z3 protein that had a distinct cytoplasmic localization. Thus, the three A3 genes of sheep and cattle encode four conserved and active proteins. These data, together with phylogenetic analyses, indicated that a similar, functionally modular A3 repertoire existed in the common ancestor of artiodactyls and primates (i.e., the ancestor of placental mammals). This mammalian ancestor therefore possessed the minimal A3 gene set, Z1-Z2-Z3, required to evolve through a remarkable series of eight recombination events into the present day eleven Z domain human repertoire. The dynamic recombination-filled history of the mammalian A3 genes is consistent with the modular nature of the locus and a model in which most of these events (especially the expansions) were selected by ancient pathogenic retrovirus infections.
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影响因子：
1.7
作者：
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通讯作者：
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影响因子：
3.7
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
Zwieg, Ann S.