Marsh J L, Wright T R
Genetics. 1986 Feb;112(2):249-65. doi: 10.1093/genetics/112.2.249.
We have analyzed two variants of Drosophila melanogaster (RS and RE) which lead to the dual phenotype of elevated DDC activity and increased resistance to dietary alpha-methyldopa relative to Oregon-R controls. Both phenotypes show tight genetic linkage to the dopa decarboxylase, Ddc, and l(2)amd genes (i.e., less than 0.05 cM distant). We find that low (Oregon-R), medium (RS) and high (RE and Canton-S) levels of DDC activity seen at both pupariation and eclosion in these strains are completely accounted for by differences in accumulation of DDC protein as measured by immunoprecipitation. Genetic reconstruction experiments in which Ddc+ and amd+ gene doses are varied show that increasing DDC activity does not lead to a measurable increase in resistance to dietary alpha-methyldopa. This suggests that the increased resistance to dietary alpha-methyldopa is not the result of increased DDC activity but, rather, results from increased l(2)amd+ activity. Both cytogenetic and molecular analyses indicate that these overproduction variants are not the result of small duplications of the Ddc and amd genes, nor are they associated with small (greater than or equal to 100 bp) insertions or deletions. Measurements of DDC activity in wild-type strains of Drosophila reveal a unimodal distribution of activity levels with the Canton-S and RE strains at the high end of the scale, the Oregon-R control at the low end and RS near the modal value. We conclude that accumulated changes in a genetic element (or elements) in close proximity to the Ddc+ and amd+ genes lead to the coordinated changes in the expression of the Ddc and amd genes in these strains.
我们分析了黑腹果蝇的两种变体（RS和RE），相对于俄勒冈-R对照，它们导致了DDC活性升高和对饮食中α-甲基多巴抗性增加的双重表型。这两种表型都与多巴脱羧酶Ddc和l(2)amd基因紧密连锁（即距离小于0.05 cM）。我们发现，在这些品系的化蛹和羽化时观察到的低（俄勒冈-R）、中（RS）和高（RE和广东-S）水平的DDC活性，完全可以通过免疫沉淀法测量的DDC蛋白积累差异来解释。改变Ddc+和amd+基因剂量的遗传重建实验表明，增加DDC活性并不会导致对饮食中α-甲基多巴的抗性有可测量的增加。这表明对饮食中α-甲基多巴抗性的增加不是DDC活性增加的结果，而是l(2)amd+活性增加的结果。细胞遗传学和分子分析均表明，这些过量生产变体不是Ddc和amd基因小重复的结果，也与小（大于或等于100 bp）插入或缺失无关。对果蝇野生型品系中DDC活性的测量揭示了活性水平的单峰分布，广东-S和RE品系处于高端，俄勒冈-R对照处于低端，RS接近峰值。我们得出结论，与Ddc+和amd+基因紧密相邻的一个或多个遗传元件的累积变化导致了这些品系中Ddc和amd基因表达的协调变化。
