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Natural variation in the sequestosome-related gene, sqst-5, underlies zinc homeostasis in Caenorhabditis elegans
PLOS Genetics ( IF 4.5 ) Pub Date : 2020-11-11 , DOI: 10.1371/journal.pgen.1008986
Kathryn S. Evans , Stefan Zdraljevic , Lewis Stevens , Kimberly Collins , Robyn E. Tanny , Erik C. Andersen

Zinc is an essential trace element that acts as a co-factor for many enzymes and transcription factors required for cellular growth and development. Altering intracellular zinc levels can produce dramatic effects ranging from cell proliferation to cell death. To avoid such fates, cells have evolved mechanisms to handle both an excess and a deficiency of zinc. Zinc homeostasis is largely maintained via zinc transporters, permeable channels, and other zinc-binding proteins. Variation in these proteins might affect their ability to interact with zinc, leading to either increased sensitivity or resistance to natural zinc fluctuations in the environment. We can leverage the power of the roundworm nematode Caenorhabditis elegans as a tractable metazoan model for quantitative genetics to identify genes that could underlie variation in responses to zinc. We found that the laboratory-adapted strain (N2) is resistant and a natural isolate from Hawaii (CB4856) is sensitive to micromolar amounts of exogenous zinc supplementation. Using a panel of recombinant inbred lines, we identified two large-effect quantitative trait loci (QTL) on the left arm of chromosome III and the center of chromosome V that are associated with zinc responses. We validated and refined both QTL using near-isogenic lines (NILs) and identified a naturally occurring deletion in sqst-5, a sequestosome-related gene, that is associated with resistance to high exogenous zinc. We found that this deletion is relatively common across strains within the species and that variation in sqst-5 is associated with zinc resistance. Our results offer a possible mechanism for how organisms can respond to naturally high levels of zinc in the environment and how zinc homeostasis varies among individuals.



中文翻译:

隔离脂质体相关基因sqst-5的自然变异是秀丽隐杆线虫锌稳态的基础

锌是必需的微量元素,可作为细胞生长发育所需的许多酶和转录因子的辅助因子。改变细胞内锌水平可以产生从细胞增殖到细胞死亡的巨大作用。为了避免这种命运,细胞已经进化出可以处理锌过多和锌缺乏的机制。锌稳态主要通过锌转运蛋白,可渗透通道和其他锌结合蛋白来维持。这些蛋白质的变异可能会影响它们与锌相互作用的能力,从而导致敏感性增加或对环境中自然锌波动的抵抗力。我们可以利用the虫线虫秀丽隐杆线虫的力量作为定量遗传学的易于处理的后生动物模型,以鉴定可能是锌反应变异的基础的基因。我们发现实验室适应的菌株(N2)具有抗药性,而来自夏威夷的天然分离株(CB4856)对微摩尔量的外源锌补充剂敏感。使用一组重组自交系,我们在染色体III的左臂和染色体V的中心确定了两个与锌反应相关的大效应数量性状基因座(QTL)。我们使用近等基因系(NIL)验证并完善了两个QTL,并确定了sqst-5中自然存在的缺失是一种与脂质体相关的基因,与对高外源锌的抗性有关。我们发现,这种缺失在物种内的各个菌株之间相对普遍,并且sqst-5的变异与锌抗性相关。我们的结果为生物体如何对环境中自然高水平的锌作出反应以及个体之间锌稳态的变化提供了一种可能的机制。

更新日期:2020-11-12
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