Molecular Evolvability In Theory And In A Bacterial Drug-Resistence Gene

基因突变是生物体基因组中的随机变化。它们几乎总是对个体有害，但确实会发生罕见的有益突变。后者的常见例子包括细菌的抗生素抗药性突变、流感病毒的疫苗抗药性和昆虫的杀虫剂抗药性。尽管它们在医学和农业上具有重要的意义，但有益的突变还没有被很好地理解，因为它们是如此罕见。一个关键问题是，两个或更多有益的突变是否相互作用，产生比预期的单独影响更大的影响。Weinreich博士和Hartl博士将在大肠杆菌中研究这一问题，他们使用了一种对广泛使用的抗生素头孢噻肟产生抗药性的基因。该基因的五种不同突变与耐药性有关。为了研究它们的相互作用，研究人员将对这些突变进行所有可能的组合，并研究它们对头孢噻肟耐药性的影响。这项拟议的研究可能会带来更广泛的好处。许多传染病是由病毒或微生物引起的，这些病毒或微生物在临床使用药物治疗时，进化得如此之快，以至于即使是最新的药物在更新的药物可以开发之前也会变得无效。对抗药性的研究将有助于更好地了解这些“超级细菌”的来源，以及艾滋病病毒等病毒的抗药性。这项研究还解决了进化论的几个一般性问题。

Genetic mutations are random changes in an organism's genome. They are almost always harmful to the individual, but rare beneficial mutations do occur. Familiar examples of the latter include mutations for antibiotic resistance in bacteria, vaccine resistance in influenza viruses, and insecticide resistance in insects. In spite of their great medical and agricultural importance, beneficial mutations are not well understood because they are so rare. One critical issue is whether two or more beneficial mutations interact to produce greater effects than would be expected from their individual effects. Drs. Weinreich and Hartl will study this issue in the bacterium Escherichia coli, using a gene for resistance to the widely used antibiotic cefotaxime. Five different mutations in that gene have been associated with resistance. To investigate their interactions, the researchers will make all possible combinations of those mutations and study their effects on cefotaxime resistance.Broad benefits are likely to flow from the proposed research. Many infectious diseases are caused by viruses or microorganisms that, in response to clinical use of drug therapy, evolve beneficial mutations so rapidly that even the newest drugs become ineffective before still newer drugs can be developed. Research on drug resistance will lead to a better understanding of the origin of these "super bugs" and of drug resistance in viruses such as HIV. The study also addresses several general questions of evolutionary theory.