Nature:真核生物基因组中大量的内含子从哪来?
2016/11/01
发表在10月27日的Nature的一篇文章回答了真核生物体的基因组中内含子是怎么来的机制。通过研究含有很多新内含子的藻类基因组,研究人员认为DNA转座子可以充当内含子序列来源。


在真核生物体的基因组中,基因区域通常被称为内含子的片段所打断。内含子是序列中断的基因,作为信使RNA的一部分必须被删除。生物学家在四十年前发现这些中断的片段。从那时起,内含子的起源变得越来越神秘,作为一个不规则的历史积累的证据,在进化过程中,很少有引入大量新的内含子的时间点。但奇怪的是现代基因组中内含子却无处不在。

这么多的内含子是怎么来的?为什么内含子积累如此不平衡?发表在10月27日的Nature上,由CNR的研究人员Jason Huff和Daniel Zilberman以及三藩州立大学的Scott Roy合作,开始回答这些问题。

要找出内含子是怎么来的机制,作者们研究了两个亲缘关系较远、有相当多新引入的内含子的藻类Micromonas pusilla和Aureococcus anophagefferens。M. pusillad有上千高度相似的剪接体内含子,还是个未解决的机制。这些内含子的单元有特别的长度和序列。他们发现新的内含子主要来自于被称为DNA转座子的遗传单元,转座子可以跳入基因组进入基因,如果它们正确地移走的话不影响蛋白质的生产。这种方式会带来新的内含子。

在它们的基因组中,短的、非自主的转座子产生成千上万的内含子。每一个转座子携带一个剪切位点。其它的剪切位点是在转座子插入时增加的,这让RNA能实现完美的拼接。序列的分布会根据密码子偏好性而增加,转座子产生的内含子也呈现同样的偏好性。


图片来自于加州大学伯克利分校网站该文章新闻报道

这些转座子插入预先存在的核小体之间,这样多个核小体附近的插入产生核小体大小的中间段。所以转座子的插入和序列的选择也许可以解释内含子的偏好以及在真核生物中盛行的核小体大小的外显子。

由于DNA转座子能在基因组中快速增值然后停止,这能解释为什么内含子戏剧性般突然出现在真核生物的进化中。这两种藻类和转座子之间的进化距离显示,这两个例子是独立产生的,提示了作者概括的机制可以对内含子是怎样产生的做常规性的解释。

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  • Mechanism for DNA transposons to generate introns on genomic scales

    The discovery of introns four decades ago was one of the most unexpected findings in molecular biology. Introns are sequences interrupting genes that must be removed as part of messenger RNA production. Genome sequencing projects have shown that most eukaryotic genes contain at least one intron, and frequently many. Comparison of these genomes reveals a history of long evolutionary periods during which few introns were gained, punctuated by episodes of rapid, extensive gain. However, although several detailed mechanisms for such episodic intron generation have been proposed, none has been empirically supported on a genomic scale. Here we show how short, non-autonomous DNA transposons independently generated hundreds to thousands of introns in the prasinophyte Micromonas pusilla and the pelagophyte Aureococcus anophagefferens. Each transposon carries one splice site. The other splice site is co-opted from the gene sequence that is duplicated upon transposon insertion, allowing perfect splicing out of the RNA. The distributions of sequences that can be co-opted are biased with respect to codons, and phasing of transposon-generated introns is similarly biased. These transposons insert between pre-existing nucleosomes, so that multiple nearby insertions generate nucleosome-sized intervening segments. Thus, transposon insertion and sequence co-option may explain the intron phase biases and prevalence of nucleosome-sized exons observed in eukaryotes. Overall, the two independent examples of proliferating elements illustrate a general DNA transposon mechanism that can plausibly account for episodes of rapid, extensive intron gain during eukaryotic evolution.

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