Abstract：
Synthetic gene drive constructs are being developed to control disease vectors, invasive species, and other pest species. In a well-mixed random mating population a sufficiently strong gene drive is expected to eliminate a target population, but it is not clear whether the same is true when spatial processes play a role. In species with an appropriate biology it is possible that drive-induced reductions in density might lead to increased inbreeding, reducing the efficacy of drive, eventually leading to suppression rather than elimination, regardless of how strong the drive is. To investigate this question we analyse a series of explicitly solvable stochastic models considering a range of scenarios for the relative timing of mating, reproduction, and dispersal and analyse the impact of two different types of gene drive, a Driving Y chromosome and a homing construct targeting an essential gene. We find in all cases a sufficiently strong Driving Y will go to fixation and the population will be eliminated, except in the one life history scenario (reproduction and mating in patches followed by dispersal) where low density leads to increased inbreeding, in which case the population persists indefinitely, tending to either a stable equilibrium or a limit cycle. These dynamics arise because Driving Y males have reduced mating success, particularly at low densities, due to having fewer sisters to mate with. Increased inbreeding at low densities can also prevent a homing construct from eliminating a population. For both types of drive, if there is strong inbreeding depression, then the population cannot be rescued by inbreeding and it is eliminated. These results highlight the potentially critical role that low-density-induced inbreeding and inbreeding depression (and, by extension, other sources of Allee effects) can have on the eventual impact of a gene drive on a target population.
摘要：
正在开发合成基因驱动构建体来控制疾病载体，入侵物种,和其他害虫物种。在混合良好的随机交配种群中，预期足够强的基因驱动会消除目标种群，但是当空间过程发挥作用时，这是否也是不清楚的。在具有适当生物学特性的物种中，驱动引起的密度降低可能导致近亲繁殖增加，降低驱动的功效，最终导致镇压而不是消除，不管动力有多强。为了研究这个问题，我们分析了一系列明确可解的随机模型，考虑了一系列交配的相对时间，繁殖，并传播和分析两种不同类型的基因驱动的影响，驱动Y染色体和靶向必需基因的归巢构建体。我们发现，在所有情况下，足够强的驱动Y都会去固定，人口将被淘汰，除了在一个生活史场景中（繁殖和交配在补丁中，然后扩散），低密度导致近亲繁殖增加，在这种情况下，人口无限期地持续存在，倾向于稳定平衡或极限循环。这些动态的出现是因为驱动Y雄性降低了交配成功率，特别是在低密度的情况下，因为有更少的姐妹交配。在低密度下增加的近亲繁殖也可以防止归巢结构消除种群。对于这两种类型的驱动器，如果有强烈的近亲繁殖抑郁症，那么人口就不能通过近亲繁殖来拯救，就会被消灭。这些结果突出了低密度诱导的近亲繁殖和近亲繁殖抑郁症的潜在关键作用(和，通过延伸,Allee效应的其他来源）可能会影响基因驱动对目标人群的最终影响。
