An Indel Polymorphism in the MtnA 3' Untranslated Region Is Associated with Gene Expression Variation and Local Adaptation in Drosophila melanogaster.
An Indel Polymorphism in the MtnA 3' Untranslated Region Is Associated with Gene Expression Variation and Local Adaptation in Drosophila melanogaster.
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DOI：
10.1371/journal.pgen.1005987
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发表时间：
2016-04
期刊：
影响因子：
4.5
通讯作者：
Parsch J
中科院分区：
文献类型：
--
作者：
Catalán A;Glaser-Schmitt A;Argyridou E;Duchen P;Parsch J
插入和缺失（indels）是物种内遗传变异的主要来源，并可能导致编码或调控序列的功能变化。在这项研究中，我们报告的indel多态性在3'非翻译区（UTR）的金属硫蛋白基因MtnA与基因表达变异的自然种群的果蝇。在3' UTR中具有49-bp缺失的MtnA的衍生等位基因在撒哈拉以南非洲以外的人群中以高频率分离。在多个大陆，缺失的频率随着纬度的增加而增加，在北方欧洲接近100%。具有缺失的果蝇比具有祖先序列的果蝇具有高4倍以上的MtnA表达。在转基因果蝇中使用报告基因构建体，我们表明3' UTR缺失显著有助于观察到的表达差异。群体遗传学分析揭示了来自北方欧洲的群体内MtnA区域的选择性扫描的特征。我们还发现3' UTR缺失与增加的氧化应激耐受性相关。这些结果表明，3' UTR缺失是选择的目标，因为它能够在北方欧洲人群中赋予增加的MtnA表达水平，这可能是由于增加的氧化应激耐受性的局部适应性优势。虽然分子变异是丰富的自然种群，了解这种变化如何影响生物体的表型，是受自然选择仍然是一个重大的挑战，在进化遗传学领域。在这里，我们表明，在果蝇金属硫蛋白A基因的非编码区的缺失突变导致基因表达显着增加，并增加在氧化应激下的生存。该缺失在三个不同的地理区域中频率很高：在北方欧洲人群中，在沿着北美东海岸的北方人群中，以及在沿沿着澳大利亚东海岸的南方人群中。在北方欧洲人群中，该缺失显示了最近正选择的群体遗传特征。因此，我们提供的证据，监管多态性，在自然种群的地方适应的基础。
Insertions and deletions (indels) are a major source of genetic variation within species and may result in functional changes to coding or regulatory sequences. In this study we report that an indel polymorphism in the 3’ untranslated region (UTR) of the metallothionein gene MtnA is associated with gene expression variation in natural populations of Drosophila melanogaster. A derived allele of MtnA with a 49-bp deletion in the 3' UTR segregates at high frequency in populations outside of sub-Saharan Africa. The frequency of the deletion increases with latitude across multiple continents and approaches 100% in northern Europe. Flies with the deletion have more than 4-fold higher MtnA expression than flies with the ancestral sequence. Using reporter gene constructs in transgenic flies, we show that the 3' UTR deletion significantly contributes to the observed expression difference. Population genetic analyses uncovered signatures of a selective sweep in the MtnA region within populations from northern Europe. We also find that the 3’ UTR deletion is associated with increased oxidative stress tolerance. These results suggest that the 3' UTR deletion has been a target of selection for its ability to confer increased levels of MtnA expression in northern European populations, likely due to a local adaptive advantage of increased oxidative stress tolerance. Although molecular variation is abundant in natural populations, understanding how this variation affects organismal phenotypes that are subject to natural selection remains a major challenge in the field of evolutionary genetics. Here we show that a deletion mutation in a noncoding region of the Drosophila melanogaster Metallothionein A gene leads to a significant increase in gene expression and increases survival under oxidative stress. The deletion is in high frequency in three distinct geographic regions: in northern European populations, in northern populations along the east coast of North America, and in southern populations along the east coast of Australia. In northern European populations the deletion shows population genetic signatures of recent positive selection. Thus, we provide evidence for a regulatory polymorphism that underlies local adaptation in natural populations.
影响因子：
3.7
作者：
Werzner A;Pavlidis P;Ometto L;Stephan W;Laurent S
通讯作者：
Laurent S