Abstract：
BACKGROUND: Some rodent species living in arid areas show elevated physiological tolerance to anti-vitamin K rodenticides (AVKs), which seems to be due to some unknown selective pressures that rodents may experience in desert habitats. Genes involved in the ϒ-carboxylation of blood coagulation, including vitamin K epoxide reductase complex, subunit 1 (Vkorc1), ϒ-glutamyl-carboxylase (Ggcx) and NAD(P)H quinone one dehydrogenase (Nqo1) are associated with anticoagulant resistance, or some levels of elevated tolerance, in rodents. To detect whether the DNA sequences of the three genes are also under natural selection in the desert rodent species, we analyzed the Vkorc1, Ggcx and Nqo1 genes of the desert rodents and compared them with other rodent species.
RESULTS: We found an accelerated evolutionary rate in Vkorc1 of desert rodents, especially in Mus spretus, Nannospalax galili and Psammomys obesus. By contrast, signals of positive selection were absent for Ggcx and Nqo1 in all species. Mapping the amino acid variations on the VKORC1 protein three-dimensional model suggested most interspecific amino acid variations occur on the outer surface of the VKORC1 pocket, whereas most intraspecific amino acid changes and known AVK resistance mutations occurred on the inner surface and endoplasmic reticulum luminal loop regions. Some desert-species-specific amino acid variations were found on the positions where known resistance mutations occurred, indicating these variations might be related to the elevated physical tolerance to AVKs in desert rodents.
CONCLUSIONS: The evolution of Vkorc1 has been accelerated in some desert rodent species, indicating genetic preadaptation to anticoagulant rodenticides. Positive selection and relaxed selection have been detected in Psammomys obesus and Nannospalax galili, indicating the two rodent species might also show tolerance to AVKs, which needs further verification. © 2022 Society of Chemical Industry.
RESULTS: We found an accelerated evolutionary rate in Vkorc1 of desert rodents, especially in Mus spretus, Nannospalax galili and Psammomys obesus. By contrast, signals of positive selection were absent for Ggcx and Nqo1 in all species. Mapping the amino acid variations on the VKORC1 protein three-dimensional model suggested most interspecific amino acid variations occur on the outer surface of the VKORC1 pocket, whereas most intraspecific amino acid changes and known AVK resistance mutations occurred on the inner surface and endoplasmic reticulum luminal loop regions. Some desert-species-specific amino acid variations were found on the positions where known resistance mutations occurred, indicating these variations might be related to the elevated physical tolerance to AVKs in desert rodents.
CONCLUSIONS: The evolution of Vkorc1 has been accelerated in some desert rodent species, indicating genetic preadaptation to anticoagulant rodenticides. Positive selection and relaxed selection have been detected in Psammomys obesus and Nannospalax galili, indicating the two rodent species might also show tolerance to AVKs, which needs further verification. © 2022 Society of Chemical Industry.
摘要：
背景：一些生活在干旱地区的啮齿动物对维生素K杀鼠剂（AVK）的生理耐受性提高，这似乎是由于啮齿动物可能在沙漠栖息地经历的一些未知的选择压力。参与血液凝固的羧基化的基因，包括维生素K环氧化物还原酶复合物，亚基1(Vkorc1)，γ-谷氨酰-羧化酶（Ggcx）和NAD（P）H醌一脱氢酶（Nqo1）与抗凝血抗性有关，或某些水平的提高的耐受性，在啮齿动物中。为了检测这三个基因的DNA序列是否也在沙漠啮齿动物物种中处于自然选择之下，我们分析了沙漠啮齿动物的Vkorc1，Ggcx和Nqo1基因，并将其与其他啮齿动物进行了比较。
结果：我们发现沙漠啮齿动物的Vkorc1进化速度加快，尤其是在spretus中，Nannospalaxgalili和Psammomysobesus。相比之下,在所有物种中，Ggcx和Nqo1均不存在阳性选择信号。在VKORC1蛋白三维模型上绘制氨基酸变异，表明大多数种间氨基酸变异发生在VKORC1口袋的外表面上。而大多数种内氨基酸变化和已知的AVK抗性突变发生在内表面和内质网腔环区.在发生已知抗性突变的位置上发现了一些沙漠物种特异性氨基酸变异，表明这些变化可能与沙漠啮齿动物对AVK的物理耐受性升高有关。
结论：在一些沙漠啮齿动物中，Vkorc1的进化加速，表明抗凝血杀鼠剂的遗传预适应。在Psammomysobesus和Nannospalaxgalili中检测到阳性选择和放松选择，表明这两种啮齿动物也可能对AVK表现出耐受性，这需要进一步核实。©2022化学工业学会。
结果：我们发现沙漠啮齿动物的Vkorc1进化速度加快，尤其是在spretus中，Nannospalaxgalili和Psammomysobesus。相比之下,在所有物种中，Ggcx和Nqo1均不存在阳性选择信号。在VKORC1蛋白三维模型上绘制氨基酸变异，表明大多数种间氨基酸变异发生在VKORC1口袋的外表面上。而大多数种内氨基酸变化和已知的AVK抗性突变发生在内表面和内质网腔环区.在发生已知抗性突变的位置上发现了一些沙漠物种特异性氨基酸变异，表明这些变化可能与沙漠啮齿动物对AVK的物理耐受性升高有关。
结论：在一些沙漠啮齿动物中，Vkorc1的进化加速，表明抗凝血杀鼠剂的遗传预适应。在Psammomysobesus和Nannospalaxgalili中检测到阳性选择和放松选择，表明这两种啮齿动物也可能对AVK表现出耐受性，这需要进一步核实。©2022化学工业学会。
