Coevolution of retroelements and tandem zinc finger genes
Coevolution of retroelements and tandem zinc finger genes
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DOI：
10.1101/gr.121749.111
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发表时间：
2011-11-01
期刊：
影响因子：
7
通讯作者：
Schneider, Sean
中科院分区：
文献类型：
--
作者：
Thomas, James H.;Schneider, Sean
脊椎动物基因组编码大量和高度可变数量的串联C2 H2锌指（串联ZF）转录因子蛋白。在哺乳动物中，大多数串联ZF基因也编码KRAB结构域（KZNF蛋白）。关于是什么力量驱动了串联ZF基因的数量和多样性，我们知之甚少。最近的研究表明，KZNF蛋白的作用之一是结合和抑制外源性逆转录病毒及其内源性对应物LTR逆转录元件的转录。我们报告了脊椎动物基因组之间的LTR逆转录元件的数量和宿主串联ZF基因的数量惊人的相关性。这种相关性是特定的LTR逆转录元件和ZF基因，并没有解释在其他基因组特征的协变。我们进一步表明，最近活跃的LTR逆转录元件与脊椎动物中最近的串联ZF基因重复相关。在灵长类动物遗传学的分支上，我们发现内源性逆转录病毒新家族的出现强烈地预示着新的重复KZNF基因的出现。我们假设逆转录病毒和LTR逆转录因子负荷驱动宿主串联ZF基因的进化。这一假说与先前描述的整个脊椎动物中重复ZF基因的分子进化模式是一致的。为了进一步探索这些模式，我们研究了34个重复的人KZNF基因对，所有这些基因对在其ZF结构域的主要核苷酸接触残基中经历了早期的分歧爆发，然后在两个重复中进行纯化选择。我们的研究结果支持了串联ZF基因进化的宿主-病原体模型，其中新的LTR逆转录元件挑战驱动宿主串联ZF基因的复制和分歧。
Vertebrate genomes encode large and highly variable numbers of tandem C2H2 zinc finger (tandem ZF) transcription factor proteins. In mammals, most tandem ZF genes also encode a KRAB domain (KZNF proteins). Very little is known about what forces have driven the number and diversity of tandem ZF genes. Recent studies suggest that one role of KZNF proteins is to bind and repress transcription of exogenous retroviruses and their endogenous counterpart LTR retroelements. We report a striking correlation across vertebrate genomes between the number of LTR retroelements and the number of host tandem ZF genes. This correlation is specific to LTR retroelements and ZF genes and was not explained by covariation in other genomic features. We further show that recently active LTR retroelements are correlated with recent tandem ZF gene duplicates across vertebrates. On branches of the primate phylogeny, we find that the appearance of new families of endogenous retroviruses is strongly predictive of the appearance of new duplicate KZNF genes. We hypothesize that retroviral and LTR retroelement burden drives evolution of host tandem ZF genes. This hypothesis is consistent with previously described molecular evolutionary patterns in duplicate ZF genes throughout vertebrates. To further explore these patterns, we investigated 34 duplicate human KZNF gene pairs, all of which underwent an early burst of divergence in the major nucleotide contact residues of their ZF domains, followed by purifying selection in both duplicates. Our results support a host-pathogen model for tandem ZF gene evolution, in which new LTR retroelement challenges drive duplication and divergence of host tandem ZF genes.