Everman Elizabeth R, Macdonald Stuart J
1200 Sunnyside Ave, University of Kansas, Molecular Biosciences, Lawrence, KS 66045, USA.
730 Van Vleet Oval, University of Oklahoma, Biology, Norman, OK 73019, USA.
bioRxiv. 2023 Jul 18:2023.07.12.548746. doi: 10.1101/2023.07.12.548746.
Copper is one of a handful of biologically necessary heavy metals that is also a common environmental pollutant. Under normal conditions, copper ions are required for many key physiological processes. However, in excess, copper quickly results in cell and tissue damage that can range in severity from temporary injury to permanent neurological damage. Because of its biological relevance, and because many conserved copper-responsive genes also respond to other non-essential heavy metal pollutants, copper resistance in is a useful model system with which to investigate the genetic control of the response to heavy metal stress. Because heavy metal toxicity has the potential to differently impact specific tissues, we genetically characterized the control of the gene expression response to copper stress in a tissue-specific manner in this study. We assessed the copper stress response in head and gut tissue of 96 inbred strains from the Synthetic Population Resource (DSPR) using a combination of differential expression analysis and expression quantitative trait locus (eQTL) mapping. Differential expression analysis revealed clear patterns of tissue-specific expression, primarily driven by a more pronounced gene expression response in gut tissue. eQTL mapping of gene expression under control and copper conditions as well as for the change in gene expression following copper exposure (copper response eQTL) revealed hundreds of genes with tissue-specific local -eQTL and many distant -eQTL. eQTL associated with , , , and exhibited genotype by environment effects on gene expression under copper stress, illuminating several tissue- and treatment-specific patterns of gene expression control. Together, our data build a nuanced description of the roles and interactions between allelic and expression variation in copper-responsive genes, provide valuable insight into the genomic architecture of susceptibility to metal toxicity, and highlight many candidate genes for future functional characterization.
铜是少数几种对生物必需的重金属之一，同时也是一种常见的环境污染物。在正常情况下，许多关键的生理过程都需要铜离子。然而，过量的铜会迅速导致细胞和组织损伤，其严重程度从暂时损伤到永久性神经损伤不等。由于其生物学相关性，并且许多保守的铜响应基因也对其他非必需重金属污染物有反应，因此铜抗性是一个有用的模型系统，可用于研究对重金属胁迫反应的遗传控制。由于重金属毒性可能对特定组织产生不同影响，我们在本研究中以组织特异性方式对铜胁迫下基因表达反应的控制进行了遗传特征分析。我们使用差异表达分析和表达数量性状位点（eQTL）定位相结合的方法，评估了来自果蝇合成群体资源（DSPR）的96个近交系的头部和肠道组织中的铜胁迫反应。差异表达分析揭示了组织特异性表达的清晰模式，主要是由肠道组织中更明显的基因表达反应驱动的。在对照和铜处理条件下基因表达的eQTL定位以及铜暴露后基因表达的变化（铜反应eQTL）揭示了数百个具有组织特异性局部eQTL和许多远距离eQTL的基因。与铜胁迫下基因表达的基因型×环境效应相关的eQTL，阐明了几种组织和处理特异性的基因表达控制模式。总之，我们的数据对铜响应基因中等位基因变异和表达变异之间的作用及相互作用进行了细致入微的描述，为金属毒性易感性的基因组结构提供了有价值的见解，并突出了许多未来功能表征的候选基因。
