Long-range regulatory polymorphisms affecting a GABA receptor constitute a quantitative trait locus (QTL) for social behavior in Caenorhabditis elegans.
Long-range regulatory polymorphisms affecting a GABA receptor constitute a quantitative trait locus (QTL) for social behavior in Caenorhabditis elegans.
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DOI：
10.1371/journal.pgen.1003157
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Bargmann CI
中科院分区：
文献类型：
--
作者：
Bendesky A;Pitts J;Rockman MV;Chen WC;Tan MW;Kruglyak L;Bargmann CI
聚集是一种在物种之间和物种内部存在差异的社会行为，为研究行为多样性的遗传基础提供了模型。在线虫秀丽隐杆线虫中，聚集受到环境背景和两种神经调节途径的调节，一种依赖于神经肽受体 NPR-1，另一种依赖于 TGF-β 家族蛋白 DAF-7。为了进一步了解聚集的遗传调控，我们描述了两种野生型线虫菌株 N2 和 CB4856 之间行为差异背后的自然变异。利用定量遗传技术，包括对染色体替换株的调查和重组自交系的 QTL 分析，除了 npr-1 和 glb-5 中两个已知的 N2 突变之外，我们还确定了三个影响聚集的新 QTL。近等基因系的精细作图定位了一个 QTL，占 N2 和 CB4856（GABA 神经递质受体基因 exp-1 转录本的 3'）之间行为差异的 5%–8%。定量互补测试表明该 QTL 影响 exp-1，将 exp-1 和 GABA 信号确定为新的聚集调节因子。 exp-1 与 daf-7 TGF-β 途径存在遗传相互作用，该途径整合了食物供应和人口密度，并且 exp-1 突变会影响 daf-7 的表达水平。我们的研究结果进一步证明，影响神经递质受体基因的遗传变异是自然行为变异的一个来源。无论是动物还是人类，正常个体在同一环境中都会表现出不同的行为。行为的自然变化部分是由于个体之间的遗传差异，部分是由于经验。绘图研究表明，自然行为变异的遗传成分很复杂，有许多基因，每个基因对观察到的行为都有少量贡献。这种复杂性使得识别个体差异的致病基因变得困难。在这里，我们使用线虫线虫来剖析一种社会行为特征，即在食物存在的情况下与其他动物聚集的倾向。我们发现两种野生型蠕虫菌株之间的行为差异是由菌株之间至少五种遗传差异造成的，其中两种差异是先前已知的。三个新基因座之一影响神经递质 GABA 的受体，该受体调节大脑的兴奋性。在之前的工作中，我们认为产生行为变异的大量基因编码神经递质受体。这种对模型动物的分析可能通过建议需要仔细检查的基因类别来帮助指导影响人类常见行为特征的遗传变异的发现。
Aggregation is a social behavior that varies between and within species, providing a model to study the genetic basis of behavioral diversity. In the nematode Caenorhabditis elegans, aggregation is regulated by environmental context and by two neuromodulatory pathways, one dependent on the neuropeptide receptor NPR-1 and one dependent on the TGF-β family protein DAF-7. To gain further insight into the genetic regulation of aggregation, we characterize natural variation underlying behavioral differences between two wild-type C. elegans strains, N2 and CB4856. Using quantitative genetic techniques, including a survey of chromosome substitution strains and QTL analysis of recombinant inbred lines, we identify three new QTLs affecting aggregation in addition to the two known N2 mutations in npr-1 and glb-5. Fine-mapping with near-isogenic lines localized one QTL, accounting for 5%–8% of the behavioral variance between N2 and CB4856, 3′ to the transcript of the GABA neurotransmitter receptor gene exp-1. Quantitative complementation tests demonstrated that this QTL affects exp-1, identifying exp-1 and GABA signaling as new regulators of aggregation. exp-1 interacts genetically with the daf-7 TGF-β pathway, which integrates food availability and population density, and exp-1 mutations affect the level of daf-7 expression. Our results add to growing evidence that genetic variation affecting neurotransmitter receptor genes is a source of natural behavioral variation. In both animals and humans, normal individuals can behave differently in the same environment. Natural variation in behavior is partly due to genetic differences between individuals and partly due to experience. Mapping studies have demonstrated that the genetic component of natural behavioral variation is complex, with many genes that each contribute a small amount to the observed behavior. This complexity has made it difficult to identify the causative genes for individual differences. Here we use the nematode worm C. elegans to dissect a social behavioral trait, the propensity to aggregate with other animals in the presence of food. We find that the behavioral differences between two wild-type worm strains result from at least five genetic differences between the strains, two of which were previously known. One of the three new loci affects a receptor for the neurotransmitter GABA, which regulates excitability in the brain. In the context of previous work, we suggest that a significant number of genes that generate behavioral variation encode neurotransmitter receptors. This analysis in a model animal may help guide discoveries of the genetic variants that affect common human behavioral traits by suggesting classes of genes to examine closely.
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影响因子：
30.8
作者：
Andersen, Erik C.;Gerke, Justin P.;Shapiro, Joshua A.;Crissman, Jonathan R.;Ghosh, Rajarshi;Bloom, Joshua S.;Felix, Marie-Anne;Kruglyak, Leonid
通讯作者：
Kruglyak, Leonid
影响因子：
29
作者：
Greer, Elisabeth R.;Perez, Carissa L.;Van Gilst, Marc R.;Lee, Brian H.;Ashrafi, Kaveh
通讯作者：
Ashrafi, Kaveh
影响因子：
3.3
作者：
Glauser, Dominique A.;Chen, Will C.;Goodman, Miriam B.
通讯作者：
Goodman, Miriam B.
影响因子：
25
作者：
Beg, AA;Jorgensen, EM
通讯作者：
Jorgensen, EM
影响因子：
30.8
作者：
Enattah, NS;Sahi, T;Järvelä, I
通讯作者：
Järvelä, I