The dynamics of transposable elements in genetically modified mosquito vectors.

摘要

The possibility of using genetically modified mosquitoes (GMMs) to control malaria has been discussed for several decades. Concrete proposals for using such methods are under development and empirical measurements permit some evaluation. Using the most recent experimental data, we model the use of transposable elements (TEs) to drive refractory genes into mosquito populations. Our models recommend a transgenic release at the beginning of the seasonal population growth phase and a transposition rate of 0.1 per TE per generation to satisfy public health goals. Concern is raised regarding the loss of linkage between the TE and refractory gene, and is heightened by the observation that TEs such as Himar1 transpose significantly more frequently once free of exogenous DNA. This has the potential to significantly diminish the success of the disease control strategy. Concerns are also raised regarding the possibility that a few transgenic mosquitoes will escape from field cages during the course of preliminary studies to test their efficacy. If TEs are used as the drive mechanism, modeling suggests that fewer than ten escapees are sufficient to establish the transgene in the population. We also analyze loss probabilities for other gene drive systems following an accidental release. Our models suggest that homing endonuclease genes and TEs are among the most invasive of the gene drive systems currently being considered. For meiotic drive strategies consisting of a drive gene and response allele, the drive gene is very capable of spreading; however the response allele requires a fitness benefit in order to spread. Drive strategies that rely on decreasing the number of wild-type mosquitoes in order to increase their own prevalence---such as Medea, Wolbachia and engineered underdominance---require either a fitness benefit or minimum release size in order to spread. Research into other drive strategies is encouraged; however all drive strategies are ultimately confronted by the economic infeasibility of transforming at least five different vectors of human malaria in order to achieve some semblance of control. Parallels are suggested between GMMs and the ill-fated Concorde supersonic airplane.