Pfefferkorn E R, Kasper L H
Exp Parasitol. 1983 Apr;55(2):207-18. doi: 10.1016/0014-4894(83)90015-2.
Mutants resistant to sinefungin (SF) and hydroxyurea (HU) were isolated from an oocyst-producing strain of Toxoplasma gondii with the aid of mutagenesis with ethylnitrosourea. These mutants were used with previously described mutants resistant to adenine arabinoside (araA) and fluorodeoxyuridine (FUDR) in genetic crosses in cats. In order to interpret the data from crosses in which all four mutants were used to infect the same cat, it was necessary to devise a mathematical expression to predict the recombination frequency for unlinked markers. This frequency was shown in theory to be half of the product of the two parental phenotype frequencies. A series of crosses in which the parental frequencies were systematically varied yielded frequencies of recombination that were in accord with this calculation. The four-way crosses in the same cat showed unlinked recombination between all markers except HU and FUDR. This pair of markers yielded no doubly resistant recombinants, suggesting complete linkage. However, linkage was excluded when a binary cross between the HU- and FUDR-resistant mutants resulted in the normal number of doubly sensitive recombinants. The lack of doubly resistant recombinants was shown to be a consequence of phenotypic suppression of HU resistance by FUDR resistance. This suppression was first demonstrated by showing that an FUDR-resistant mutant selected from an HU-resistant parasite lost the HU resistance. The phenotypically suppressed HU-resistant gene was revealed by genetic crosses with wild type T. gondii. Although both parental stains were sensitive to HU, some of the progeny parasites were resistant.
借助乙基亚硝基脲诱变，从一株产生卵囊的刚地弓形虫中分离出对杀稻瘟菌素（SF）和羟基脲（HU）具有抗性的突变体。这些突变体与先前描述的对阿糖腺苷（araA）和氟脱氧尿苷（FUDR）具有抗性的突变体一起用于猫的遗传杂交实验。为了解释使用所有四个突变体感染同一只猫的杂交实验数据，有必要设计一个数学表达式来预测不连锁标记的重组频率。理论上，该频率为两个亲本表型频率乘积的一半。一系列系统改变亲本频率的杂交实验产生的重组频率与该计算结果一致。在同一只猫中进行的四向杂交实验表明，除HU和FUDR外，所有标记之间均存在不连锁重组。这一对标记未产生双抗性重组体，表明它们完全连锁。然而，当HU抗性和FUDR抗性突变体之间的二元杂交产生正常数量的双敏感重组体时，排除了连锁关系。结果表明，缺乏双抗性重组体是由于FUDR抗性对HU抗性的表型抑制所致。通过显示从HU抗性寄生虫中选出的FUDR抗性突变体失去了HU抗性，首次证明了这种抑制作用。通过与野生型刚地弓形虫进行遗传杂交，揭示了表型受抑制的HU抗性基因。虽然两个亲本菌株对HU均敏感，但一些子代寄生虫具有抗性。
