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功能性A-to-I mRNA编辑的一个终极问题:为什么不是基因组中的G?

An Ultimate Question for Functional A-to-I mRNA Editing: Why Not a Genomic G?

作者信息

Xie Qiuhua, Duan Yuange

机构信息

Department of Entomology and State Key Laboratory of Agricultural and Forestry Biosecurity, MOA Key Lab of Pest Monitoring and Green Management, College of Plant Protection, China Agricultural University, Beijing, 100193, China.

出版信息

J Mol Evol. 2025 Apr;93(2):185-192. doi: 10.1007/s00239-025-10238-8. Epub 2025 Feb 18.

DOI:10.1007/s00239-025-10238-8
PMID:39964487
Abstract

A-to-I mRNA editing resembles A-to-G mutations. Functional mRNA editing, representing only a corner of total editing events, can be inferred from the experimental removal of editing. However, it is intuitive to ask why evolution chose RNA editing rather than directly (and simply) changing the genomic sequence to G? If G is better than A, then drift or constructive neutral evolution (CNE) theory can explain the emergence of such editing, but it is still unclear why the exemplified conserved editing is perfectly maintained without observing any subsequent A-to-G DNA mutations? Virtually every functional and conserved mRNA editing site faces this ultimate question until one justifies that being editable is better than a hardwired genomic allele. While the advantage of editability has been validated in fungi, this ultimate question has not been answered for any functional editing sites in animals. By providing several conceptual arguments and specific examples, we propose that proving the evolutionary adaptiveness of an editing site is far more difficult than revealing its function.

摘要

A-to-I mRNA编辑类似于A-to-G突变。功能性mRNA编辑只是总编辑事件的一角,可通过实验性去除编辑来推断。然而,很自然会问,为什么进化选择了RNA编辑而不是直接(且简单地)将基因组序列改变为G呢?如果G比A更好,那么漂变或建设性中性进化(CNE)理论可以解释这种编辑的出现,但仍不清楚为什么例证性的保守编辑能完美维持,却未观察到任何后续的A-to-G DNA突变?几乎每个功能性且保守的mRNA编辑位点都面临这个终极问题,除非有人能证明可编辑性比固定的基因组等位基因更具优势。虽然可编辑性的优势已在真菌中得到验证,但动物中任何功能性编辑位点的这个终极问题都尚未得到解答。通过提供几个概念性论据和具体例子,我们提出,证明一个编辑位点的进化适应性远比揭示其功能困难得多。

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本文引用的文献

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An orthology-based methodology as a complementary approach to retrieve evolutionarily conserved A-to-I RNA editing sites.基于同源性的方法作为一种补充方法,以检索进化上保守的 A-to-I RNA 编辑位点。
RNA Biol. 2024 Jan;21(1):29-45. doi: 10.1080/15476286.2024.2397757. Epub 2024 Sep 10.
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Narrowing down the candidates of beneficial A-to-I RNA editing by comparing the recoding sites with uneditable counterparts.通过比较编辑和非编辑的靶点,缩小有益的 A-to-I RNA 编辑的候选范围。
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