Negative selection pressure against premature protein truncation is reduced by alternative splicing and diploidy.
Negative selection pressure against premature protein truncation is reduced by alternative splicing and diploidy.
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通过选择性剪接和二倍体减少了针对过早蛋白质截断的负选择压力。
DOI：
10.1016/j.tig.2004.07.009
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Lee,ChristopherJ
中科院分区：
文献类型：
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作者：
Xing,Yi;Lee,ChristopherJ
选择性剪接在许多基因组中的重要性引发了关于其在进化中的作用的有趣问题。我们分析了13384全长转录异构体从人类和2227异构体从小鼠，以确定序列包含提前终止密码子（PTC），可能是mRNA无义介导的衰变的目标。 我们发现，选择性剪接异构体有一个更高的频率PTC（11.1%）相比，每个基因的主要转录形式（3.7%）。在通常以单拷贝形式表达的X染色体上，总体PTC率要低得多（3.5%，二倍体常染色体上为8.9%），并且选择性剪接的作用增强。因此，二倍体和选择性剪接每个增加约三倍的耐PTC，作为近似加性效应。这些数据表明，无义介导的衰变本身可能会减少负选择压力在进化过程中，通过快速降解的异常转录，可能会产生显性负表型。
The importance of alternative splicing in many genomes has raised interesting questions about its role in evolution. We analyzed 13 384 full-length transcript isoforms from human and 2227 isoforms from mouse to identify sequences containing premature termination codons (PTCs) that are likely targets of mRNA nonsense-mediated decay. We found that alternatively spliced isoforms have a much higher frequency of PTCs (11.1%) compared with the major transcript form of each gene (3.7%). On the X chromosome, which is generally expressed as a single copy, the overall PTC rate was much lower (3.5%, versus 8.9% on diploid autosomes), and the effect of alternative splicing was enhanced. Thus, diploidy and alternative splicing each increased tolerance for PTC by about threefold, as approximately additive effects. These data suggest that nonsense mediated decay might itself reduce negative selection pressure during evolution, via rapid degradation of aberrant transcripts that might yield dominant negative phenotypes.