Department of Life Sciences, Imperial College London, Silwood Park, Ascot, Berks SL5 7PY, United Kingdom.
Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):E874-80. doi: 10.1073/pnas.1110717108. Epub 2011 Oct 5.
Malaria continues to impose a substantial burden on human health. We have previously proposed that biological approaches to control the mosquito vector of disease could be developed using homing endonuclease genes (HEGs), a class of selfish or parasitic gene that exists naturally in many microbes. Recent lab studies have demonstrated that HEGs can function in mosquitoes. We constructed and analyzed a model of mosquito population genetics and malaria epidemiology to determine how well HEGs need to function in order to have a significant effect on the burden of disease. Our model, combined with currently available data, indicates that populations of Anopheles gambiae could be eliminated by releasing 2-3 HEGs targeting female fertility genes, or a driving-Y chromosome that is transmitted to 75-96% of progeny. Combinations of fertility-targeting HEGs and Y drive may also be effective. It is possible to eliminate the disease without eliminating the vector, but the parameter space producing this outcome appears to be small. HEGs causing a quantitative reduction in adult survival can be more effective than those targeting female fertility, but the selection coefficients that need to be imposed are still large, unless many HEGs are to be released. Simulations show that HEG-based strategies can be effective over socially relevant time frames. Important limiting assumptions of the models are that there is only a single vector species, and we model a homogeneous population, not a landscape. Nevertheless, we conclude that HEG-based approaches could have a transformational effect on malaria control efforts.
疟疾仍然对人类健康造成重大负担。我们之前曾提出，可以利用归巢内切酶基因（HEGs）开发控制疾病蚊媒的生物学方法，HEGs 是一类自然存在于许多微生物中的自私或寄生基因。最近的实验室研究表明，HEGs 可以在蚊子中发挥作用。我们构建并分析了一种蚊子种群遗传学和疟疾流行病学模型，以确定 HEGs 需要发挥多大作用才能对疾病负担产生重大影响。我们的模型结合目前可用的数据表明，通过释放 2-3 种针对雌性生育基因的 HEGs 或传递给 75-96%后代的驱动 Y 染色体，可以消除冈比亚按蚊种群。针对生育基因的 HEG 与 Y 驱动的组合也可能有效。虽然有可能在不消灭媒介的情况下消除疾病，但产生这种结果的参数空间似乎很小。导致成年存活率定量减少的 HEG 可能比针对雌性生育的 HEG 更有效，但需要施加的选择系数仍然很大，除非要释放许多 HEG。模拟表明，基于 HEG 的策略可以在具有社会相关性的时间范围内有效。模型的重要限制假设是只有一种媒介物种，并且我们模型是同质种群，而不是景观。尽管如此，我们得出的结论是，基于 HEG 的方法可能会对疟疾控制工作产生变革性影响。
