NMD and the evolution of eukaryotic gene structure
NMD and the evolution of eukaryotic gene structure
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NMD与真核基因结构的进化
DOI：
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
Douglas G. Scofield
中科院分区：
文献类型：
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作者：
M. Lynch;Xin Hong;Douglas G. Scofield
所有细胞都面临着来自突变等位基因的不良转录物，但从其他正常DNA产生异常转录物可能是一个更大的挑战。含有提前终止密码子（PTC）的有问题的转录本的相当大一部分通过无义介导的mRNA衰变（NMD）途径被消除。系统发育分析表明，NMD和它在哺乳动物中依赖的外显子连接复合体（EJC）是古老的，这增加了NMD与内含子早期关联的可能性。这可能有助于解释为什么内含子能够在茎真核生物中增殖到明显相当大的程度，尽管内含子对其宿主基因施加了突变负担。NMD和内含子之间的长期进化阿索也为多细胞物种基因中内含子的非随机空间分布和现代物种中内含子定殖的明显减缓（和可能的稳定）提供了可能的解释。几个谱系，所有这些都几乎没有祖先内含子，似乎已经失去了NMD和EJC，这些分类群具有非常简单的基因组特征，最大限度地减少了产生错误转录本的机会。这些想法的验证将需要经验的工作之间的协调程度NMD，EJC，和内含子的位置分布在不同的系统发育谱系的广泛的基因阵列。
All cells are confronted with undesirable transcripts derived from mutant alleles, but the production of aberrant transcripts from otherwise normal DNA may be an even greater challenge. The substantial fraction of problematical transcripts containing premature termination codons (PTCs) are subject to elimination by the nonsense-mediated mRNA decay (NMD) pathway. Phylogenetic analysis suggests that NMD and the exon junction complex (EJC) upon which it depends in mammals (see chapter by Maquat) are ancient, raising the possibility of an early association of NMD with introns. This may help explain why introns were able to proliferate to an apparently considerable degree in the stem eukaryote, despite the mutational burden that introns impose upon their host genes. A long-term evolutionary asso- ciation between NMD and introns also provides a possible explanation for the nonrandom spatial distribution of introns in the genes of multicellular species and for an apparent slow- down (and possible stabilization) of intron colonization in modern species. Several lineages, all of which are nearly devoid of ancestral introns, appear to have lost NMD and the EJC, and these taxa have exceptionally simple genomic features that minimize the chances of producing erroneous transcripts. Validation of these ideas will require empirical work on the degree of coordination between NMD, the EJC, and the locations of introns in a wide array of genes distributed across diverse phylogenetic lineages.