活的有机体适应他们的环境,这种对环境变化的适应性反应受到基因组和表观基因组成分的影响。由于适应支撑着对压力源的容忍度,在评估环境化学品的不利后果时,考虑生物适应性至关重要,比如杀生物剂。Daphnid研究揭示了特定种群或克隆对环境化学物质的敏感性存在差异,以及物种之间。这项研究旨在确定对化学物质的敏感性是否受到种内变异的影响,以及这种敏感性是否取决于水蚤种群的遗传和表观遗传背景。我们使用一种综合方法来评估5-氯-2-甲基-4-异噻唑啉-3-酮和2-甲基-4-异噻唑啉-3-酮(CMIT/MIT)混合物的比较毒性,一种常用的异噻唑啉酮杀生物剂,通过测量死亡率,繁殖,生理特征,全局DNA甲基化,以及物种和菌株水平的蛋白质组表达。结果表明,同种品系之间对CMIT/MIT的敏感性变化(Daphniapulex;DPRvs.DPA菌株)可能超过同类物种之间观察到的(D.麦格纳vs.D.pulexDPR菌株)。在控制条件下,DPR(对CMIT/MIT最敏感的菌株)的特点是体型较大,更高的心率,与对应的DNA甲基化(DPA)相比,全球DNA甲基化水平更高,和蛋白质组谱在两个菌株之间有所不同。特别是,该研究确定了CMIT/MIT对LC20的菌株特异性表观遗传和蛋白质组学反应,证明与观察到的表型差异和对CMIT/MIT的敏感性相关的推定关键蛋白质和生物学途径。某些蛋白质的下调(例如,SAM合成酶,GSTs,血红蛋白,和角质层蛋白)和DNA低甲基化可作为异噻唑啉酮毒性的不良结局途径(AOP)的关键事件(KE)。我们的发现表明,遗传变异和表观遗传修饰都可以导致对化学物质敏感性的种内变异。这种变化应该在化学物质的生态风险评估框架中考虑。我们建议对甲基化基因区域进行进一步分析,并观察跨代效应,以验证遗传和表观遗传因素之间的串扰在表型和蛋白质表达中的作用。数据可用性:蛋白质组数据可在补充材料中获得。
Living organisms adapt to their environment, and this adaptive response to environmental changes is influenced by both genomic and epigenomic components. As adaptation underpins tolerance to stressors, it is crucial to consider biological adaptation in evaluating the adverse outcomes of environmental chemicals, such as biocides. Daphnid studies have revealed differences in sensitivity to environmental chemicals between conspecific populations or clones, as well as between species. This
study aimed to identify whether sensitivity to chemicals is subject to intraspecific variation, and whether this sensitivity depends on the genetic and epigenetic backgrounds of the daphnid population. We used an integrative approach to assess the comparative toxicity of a mixture of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), a commonly used isothiazolinone biocide, by measuring mortality, reproduction, physiological traits, global DNA methylation, and proteomic expression at the species and strain levels. The results showed that the variation in sensitivity to CMIT/MIT between conspecific strains (Daphnia pulex; DPR vs. DPA strains) could exceed that observed between congeneric species (D. magna vs. D. pulex DPR strain). Under the control conditions, DPR (the strain most sensitive to CMIT/MIT) was characterized by a larger body size, a higher heart rate, and a higher level of global DNA methylation compared to its counterpart (DPA), and proteome profiles differed between the two strains. Particularly, the
study identified strain-specific epigenetic and proteomic responses to LC20 of CMIT/MIT, demonstrating putative critical proteins and biological pathways associated with the observed differences in phenotype and sensitivity to CMIT/MIT. Downregulation of certain proteins (e.g., SAM synthase, GSTs, hemoglobin, and cuticle proteins) and DNA hypomethylation can be proposed as key events (KEs) of adverse outcome pathway (AOP) for isothiazolinone toxicity. Our findings indicate that both genetic variations and epigenetic modifications can lead to intraspecific variation in sensitivity to chemicals, and this variation should be considered in the ecological risk assessment framework for chemical substances. We suggest conducting further analysis on methylated gene regions and observing transgenerational effects to verify the role of crosstalk between genetic and epigenetic factors in phenotypic and protein expressions. DATA AVAILABILITY: Proteomic data is available in supplementary materials.