Abstract:
Adenosine-to-inosine (A-to-I) RNA editing recodes the genetic information. Apart from diversifying the proteome, another tempting advantage of RNA recoding is to correct deleterious DNA mutation and restore ancestral allele. Solid evidences for beneficial restorative editing are very rare in animals. By searching for \"convergent recoding\" under a phylogenetic context, we proposed this term for judging the potential restorative functions of particular editing site. For the well-known mammalian Gln>Arg (Q>R) recoding site, its ancestral state in vertebrate genomes was the pre-editing Gln, and all 470 available mammalian genomes strictly avoid other three equivalent ways to achieve Arg in protein. The absence of convergent recoding from His>Arg, or synonymous mutations on Gln codons, could be attributed to the strong maintenance on editing motif and structure, but the absence of direct A-to-G mutation is extremely unexpected. With similar ideas, we found cases of convergent recoding in Drosophila genus, reducing the possibility of their restorative function. In summary, we defined an interesting scenario of convergent recoding, the occurrence of which could be used as preliminary judgements for whether a recoding site has a sole restorative role. Our work provides novel insights to the natural selection and evolution of RNA editing.
摘要:
腺苷到肌苷(A到I)RNA编辑重新编码遗传信息。除了使蛋白质组多样化,RNA重新编码的另一个诱人的优势是纠正有害的DNA突变并恢复祖先等位基因。有益的恢复性编辑的可靠证据在动物中非常罕见。通过在系统发育环境下搜索“收敛重新编码”,我们提出这个术语来判断特定编辑网站的潜在恢复功能。对于众所周知的哺乳动物Gln>Arg(Q>R)重编码位点,它在脊椎动物基因组中的祖先状态是编辑前的Gln,和所有470可用的哺乳动物基因组严格避免其他三种等效方式来实现蛋白质中的Arg。从他的>Arg中没有收敛的重新编码,或者Gln密码子的同义突变,可以归因于对编辑主题和结构的强大维护,但是没有直接的A到G突变是非常出乎意料的。有了类似的想法,我们在果蝇属中发现了会聚重新编码的病例,降低其恢复功能的可能性。总之,我们定义了一个有趣的收敛重新编码场景,其发生可以用作对重新编码网站是否具有唯一恢复作用的初步判断。我们的工作为RNA编辑的自然选择和进化提供了新的见解。