An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons.
An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons.
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DOI：
10.1038/nature13760
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发表时间：
2014-12-11
期刊：
影响因子：
64.8
通讯作者：
Haussler, David
中科院分区：
文献类型：
--
作者：
Jacobs, Frank M. J.;Greenberg, David;Ngan Nguyen;Haeussler, Maximilian;Ewing, Adam D.;Katzman, Sol;Paten, Benedict;Salama, Sofie R.;Haussler, David
在整个进化过程中，灵长类动物的基因组已经被反转录转座子插入波修改。对于每一波，宿主最终都会找到一种方法来抑制反转录转座子转录，并阻止进一步的插入。在小鼠胚胎干细胞（mESC）中，逆转录转座子的转录沉默需要TRIM 28（KAP 1）及其抑制复合物，其可以被KRAB锌指蛋白（如鼠特异性ZFP 809）募集到靶位点，ZFP 809结合整合的鼠白血病病毒DNA元件并募集KAP 1来抑制它们。KZNF基因是灵长类中增长最快的基因家族之一，这种扩展被假设为使灵长类能够对新出现的逆转录转座子做出反应。然而，KZNF基因的身份目前在人类基因组中活跃的反转录转座子，如SINE-VNTR-Alu（SVA）和长分散核元件-1（L1），是未知的。我们发现，两个灵长类特异性KZNF基因迅速进化，以抑制这两个不同的逆转录转座子家族后不久，他们开始在我们的祖先基因组中传播。ZNF 91在8-12 MYA经历了一系列结构变化，使其能够抑制SVA元素。ZNF 93更早地进化以抑制灵长类动物L1谱系，直到约12.5 MYA，当L1 PA 3-亚家族通过清除ZNF 93结合位点而逃脱ZNF 93的限制时。我们的数据支持一个模型，其中KZNF基因扩增限制了新出现的逆转录转座子类的活性，随后这些逆转录转座子发生突变以逃避阻遏，这是一个可以解释谱系特异性KZNF基因快速扩增的事件循环。
Throughout evolution, primate genomes have been modified by waves of retrotransposon insertions. For each wave, the host eventually finds a way to repress retrotransposon transcription and prevent further insertions. In mouse embryonic stem cells (mESCs), transcriptional silencing of retrotransposons requires TRIM28 (KAP1) and it’s repressive complex, which can be recruited to target sites by KRAB zinc finger proteins such as murine-specific ZFP809 which binds to integrated murine leukemia virus DNA elements and recruits KAP1 to repress them. KZNF genes are one of the fastest growing gene families in primates and this expansion is hypothesized to enable primates to respond to newly emerged retrotransposons. However, the identity of KZNF genes battling retrotransposons currently active in the human genome, such as SINE-VNTR-Alu (SVA) and Long Interspersed Nuclear Element-1 (L1), is unknown. We find that two primate-specific KZNF genes rapidly evolved to repress these two distinct retrotransposon families shortly after they began to spread in our ancestral genome. ZNF91 underwent a series of structural changes 8-12 MYA that enabled it to repress SVA elements. ZNF93 evolved earlier to repress the primate L1 lineage until ~12.5 MYA when the L1PA3-subfamily escaped ZNF93’s restriction through purge of the ZNF93 binding site. Our data support a model where KZNF gene expansion limits the activity of newly emerged retrotransposon classes, and this is followed by mutations in these retrotransposons to evade repression, a cycle of events that could explain the rapid expansion of lineage-specific KZNF genes.
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