Eukaryotic RNA-guided endonucleases evolved from a unique clade of bacterial enzymes.

Eukaryotic RNA-guided endonucleases evolved from a unique clade of bacterial enzymes.
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DOI:
10.1093/nar/gkad1053
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发表时间:
2023-12-11
影响因子:
14.9
通讯作者:
Doudna JA
Doudna JA
中科院分区:
生物学2区
文献类型:
--
作者:
Yoon PH;Skopintsev P;Shi H;Chen L;Adler BA;Al-Shimary M;Craig RJ;Loi KJ;DeTurk EC;Li Z;Amerasekera J;Trinidad M;Nisonoff H;Chen K;Lahiri A;Boger R;Jacobsen S;Banfield JF;Doudna JA

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RNA引导的核酸内切酶构成了包括适应性免疫、转座和基因组编辑在内的各种生物学过程和技术的关键。其中一些酶是IS200/IS605和IS607转座子家族的插入序列(IS)的组成部分。这两个IS家族都编码TnpA转座酶和TnpB核酸酶,TnpB核酸酶是CRISPR-Cas12s的祖先,由RNA引导。在真核生物中,TnpB同源物以两种不同的类型出现,Fanzor1s和Fanzor2s。我们分析了原核生物TnpB和真核生物Fanzors之间的进化关系,发现Fanzor1和Fanzor2都来自IS607 TnpB的单一谱系,具有异常的活性位点排列。Fanzors的广泛存在意味着IS607 TnpB这一特殊谱系的特性特别适合于真核生物的适应。对IS607TnpB和Fanzor1s的生化分析揭示了TnpB和Fanzor1s与其同源转座酶共同进化的共同策略。总之,我们的结果提供了一个新的序列进化模型,从IS607TnpB到Fanzor2s,再从Fanzor2s到Fanzor1s,详细说明了原核起源的基因是如何进化的,从而在真核生物中产生新的蛋白质家族。
RNA-guided endonucleases form the crux of diverse biological processes and technologies, including adaptive immunity, transposition, and genome editing. Some of these enzymes are components of insertion sequences (IS) in the IS200/IS605 and IS607 transposon families. Both IS families encode a TnpA transposase and a TnpB nuclease, an RNA-guided enzyme ancestral to CRISPR-Cas12s. In eukaryotes, TnpB homologs occur as two distinct types, Fanzor1s and Fanzor2s. We analyzed the evolutionary relationships between prokaryotic TnpBs and eukaryotic Fanzors, which revealed that both Fanzor1s and Fanzor2s stem from a single lineage of IS607 TnpBs with unusual active site arrangement. The widespread nature of Fanzors implies that the properties of this particular lineage of IS607 TnpBs were particularly suited to adaptation in eukaryotes. Biochemical analysis of an IS607 TnpB and Fanzor1s revealed common strategies employed by TnpBs and Fanzors to co-evolve with their cognate transposases. Collectively, our results provide a new model of sequential evolution from IS607 TnpBs to Fanzor2s, and Fanzor2s to Fanzor1s that details how genes of prokaryotic origin evolve to give rise to new protein families in eukaryotes.
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