Prusiner Stanley B, McCarty Maclyn
Institute for Neurodegenerative Diseases, Department of Neurology, University of California, San Francisco, California 94143, USA.
Annu Rev Genet. 2006;40:25-45. doi: 10.1146/annurev.genet.40.121505.133522.
The resemblance between the discoveries that DNA is the basis of heredity and that prions are infectious proteins is remarkable. Though four decades separated these two discoveries, the biochemical methodologies and scientific philosophies that were employed are surprisingly similar. In both cases, bioassays available at the time that the projects were initiated proved to be inadequate to support purification studies. Improved bioassays allowed the transforming principle (TP) to be purified from pneumococci and prions from scrapie-infected hamster brains. Publications describing TP as composed of DNA prompted some scientists to contend that undetected proteins must contaminate TP enriched fractions. The simplicity of DNA was thought to prevent it from encoding genetic information. By the time prions were discovered, the genomes of all infectious pathogens including viruses, bacteria, fungi and parasites had been shown to be comprised of nucleic acids and so an antithetical refrain became widely echoed: DNA or RNA molecules must be hiding among the proteins of prions. Finding the unexpected and being asked to demonstrate unequivocally the absence of a possible contaminant represent uncanny parallels between the discoveries that DNA encodes the genotype and that prions are infectious proteins.
DNA是遗传基础的发现与朊病毒是感染性蛋白质的发现之间的相似之处非常显著。尽管这两个发现相隔了四十年,但所采用的生化方法和科学理念却惊人地相似。在这两个案例中,项目启动时可用的生物测定法都被证明不足以支持纯化研究。改进后的生物测定法使得转化因子(TP)能够从肺炎球菌中纯化出来,朊病毒能够从感染瘙痒病的仓鼠脑中纯化出来。将TP描述为由DNA组成的出版物促使一些科学家争辩说,未检测到的蛋白质一定污染了富含TP的组分。DNA的简单性被认为使其无法编码遗传信息。到发现朊病毒的时候,所有传染性病原体(包括病毒、细菌、真菌和寄生虫)的基因组都已被证明由核酸组成,因此一种相反的论调广泛流传:DNA或RNA分子一定隐藏在朊病毒的蛋白质之中。发现意外情况并被要求明确证明不存在可能的污染物,这在DNA编码基因型的发现和朊病毒是感染性蛋白质的发现之间呈现出不可思议的相似之处。