Tandem duplications lead to novel expression patterns through exon shuffling in Drosophila yakuba.
Tandem duplications lead to novel expression patterns through exon shuffling in Drosophila yakuba.
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DOI：
10.1371/journal.pgen.1006795
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发表时间：
2017-05
期刊：
影响因子：
4.5
通讯作者：
Thornton KR
中科院分区：
文献类型：
--
作者：
Rogers RL;Shao L;Thornton KR
解释串联复制影响的一个常见假设是，由于拷贝数的变化，整个基因复制通常会导致基因表达的加性变化。在这里，我们使用来自果蝇雅库巴种群样本的全基因组RNA-seq数据来验证这一‘基因剂量’假说。我们观察到几乎没有证据表明，对捕获5‘和3’UTRs的完整转录复制做出反应时，表达发生了变化。在全基因复制中，我们观察到有证据表明，跨拷贝的剂量共享很可能是常见的。整个基因复制后缺乏表达变化，这表明大多数基因受到严格的调控，因此对基因拷贝数的变化不敏感。相反，我们观察到由于调控元件的改组和通过串联复制创建嵌合结构而导致的表达水平的变化。此外，我们观察到来自串联复制的30个从头基因结构，其中23个形成并在睾丸中表达。因此，串联复制的价值可能比基因剂量的简单变化更复杂。串联复制后嵌合基因形成的共同调控效应可能解释了它们对基因组进化的贡献。所附工作表明，整个基因复制很少影响基因表达，而不是普遍认为重复基因的适应价值与基因拷贝数导致的基因表达的加性变化有关。我们进一步解释了产生改组基因结构的串联复制如何能够迫使基因序列上调、从头基因产生和转录水平的多重变化。这些结果表明，串联复制可以产生新的基因，这些基因是与先前理论所建议的更极端的表达变化相关的即刻新颖性的来源。此外，这些基因表达变化是有益和致病突变的潜在来源，与人类和其他后生动物的临床和医学遗传学直接相关。
One common hypothesis to explain the impacts of tandem duplications is that whole gene duplications commonly produce additive changes in gene expression due to copy number changes. Here, we use genome wide RNA-seq data from a population sample of Drosophila yakuba to test this ‘gene dosage’ hypothesis. We observe little evidence of expression changes in response to whole transcript duplication capturing 5′ and 3′ UTRs. Among whole gene duplications, we observe evidence that dosage sharing across copies is likely to be common. The lack of expression changes after whole gene duplication suggests that the majority of genes are subject to tight regulatory control and therefore not sensitive to changes in gene copy number. Rather, we observe changes in expression level due to both shuffling of regulatory elements and the creation of chimeric structures via tandem duplication. Additionally, we observe 30 de novo gene structures arising from tandem duplications, 23 of which form with expression in the testes. Thus, the value of tandem duplications is likely to be more intricate than simple changes in gene dosage. The common regulatory effects from chimeric gene formation after tandem duplication may explain their contribution to genome evolution. The enclosed work shows that whole gene duplications rarely affect gene expression, in contrast to widely held views that the adaptive value of duplicate genes is related to additive changes in gene expression due to gene copy number. We further explain how tandem duplications that create shuffled gene structures can force upregulation of gene sequences, de novo gene creation, and multifold changes in transcript levels. These results show that tandem duplications can produce new genes that are a source of immediate novelty associated with more extreme expression changes than previously suggested by theory. Further, these gene expression changes are a potential source of both beneficial and pathogenic mutations, immediately relevant to clinical and medical genetics in humans and other metazoans.