Davis S, Bax N, Grewe P
School of Mathematics and Statistics, University College, UNSW, Australia.
J Theor Biol. 2001 Sep 7;212(1):83-98. doi: 10.1006/jtbi.2001.2357.
A novel form of underdominance is suggested as a mechanism that is able to drive desired genes into pest populations through the release of transgenic individuals over one or more generations. Such a mechanism is urgently needed by those working to reduce the impact of malaria by releasing strains of Anopheles, the vector of the disease, that are not susceptible to malaria parasites. We use simple population genetics models to quantify the benefits conferred when heterozygous genotypes, arising from matings between introduced and wild individuals, are not viable. In a randomly mating population, underdominant systems accelerate introgression of desired alleles and allow the release of individuals to be discontinued once the frequency of transgenic alleles attains a threshold. A set of two constructs, which together are selectively neutral but lethal when one is carried without the other, are found to produce dynamics that are characteristic of underdominant systems. When these constructs are carried on non-homologous chromosomes, then the ratio of released to natural born individuals need only be greater than 3:100 for introgression to occur. Furthermore, the threshold for the gene frequencies over which the introduced genes are expected to become fixed upon discontinuing the release of transgenic individuals is surprisingly low. The location of the threshold suggests that the introduced genes are expected to spread in space, at least locally. For the first time, the prospect of a practical drive mechanism for the genetic manipulation of pest populations is raised.
一种新形式的杂合劣势被认为是一种机制，它能够通过一代或多代释放转基因个体，将所需基因引入害虫种群。那些致力于通过释放对疟原虫不敏感的疟疾病媒按蚊品系来减少疟疾影响的人迫切需要这样一种机制。我们使用简单的群体遗传学模型来量化当引入个体与野生个体交配产生的杂合基因型不可存活时所带来的益处。在随机交配的种群中，杂合劣势系统加速了所需等位基因的渗入，并且一旦转基因等位基因的频率达到阈值，就可以停止个体的释放。发现一组两个构建体，它们在一起时是选择性中性的，但当一个构建体单独存在而没有另一个时是致死的，会产生杂合劣势系统特有的动态。当这些构建体位于非同源染色体上时，为了发生渗入，释放个体与自然出生个体的比例只需大于3:100。此外，在停止释放转基因个体后，预期引入基因会固定下来的基因频率阈值出奇地低。阈值的位置表明引入基因有望在空间中传播，至少在局部范围内。首次提出了一种用于害虫种群基因操纵的实用驱动机制的前景。
