Evading resistance to gene drives.
Evading resistance to gene drives.
复制标题
DOI：
10.1093/genetics/iyaa040
复制
发表时间：
2021-02-09
期刊：
影响因子：
3.3
通讯作者：
Bull JJ
中科院分区：
文献类型：
--
作者：
Gomulkiewicz R;Thies ML;Bull JJ
基因驱动提供了改变甚至抑制无数动植物野生种群的可能性，而CRISPR技术现在提供了改造它们的技术可行性。然而，种群抑制基因驱动倾向于选择抗性，如果它出现。在这里，我们开发了数学和计算模型来确定抑制驱动将逃避阻力的条件，即使阻力最初存在。以前的模型假设阻力是等位基因驱动。我们放宽了这一假设，并表明阻力和驱动位点之间的连锁对抗性的进化至关重要，并且抗性的进化需要两个位点之间的（负）连锁不平衡。当两个基因座不连接或部分不连接时，导致有限不生存的抑制驱动可以进化为固定，同时只引起抗性频率的轻微增加。一旦固定，驱动等位基因不再选择抗性。我们的分析表明，在引起中度抑制的基因驱动中，毒素解毒剂系统比归巢驱动更不容易选择抗性。中等效果的单一驱动可能只会导致适度的种群抑制，但多个驱动（可能依次传递）将允许任意程度的抑制。阻力进化最有利的情况似乎是抑制归巢驱动，其中阻力占主导地位，并完全抑制传输失真；抗性杂合子或隐性抗性的部分抑制不容易产生抗性进化。鉴于现在有可能设计出能够绕过等位基因抗性的基于crispr的基因驱动，这种设计可能允许设计出有效抵抗抗性的抑制基因驱动。
Gene drives offer the possibility of altering and even suppressing wild populations of countless plant and animal species, and CRISPR technology now provides the technical feasibility of engineering them. However, population-suppression gene drives are prone to select resistance, should it arise. Here, we develop mathematical and computational models to identify conditions under which suppression drives will evade resistance, even if resistance is present initially. Previous models assumed resistance is allelic to the drive. We relax this assumption and show that linkage between the resistance and drive loci is critical to the evolution of resistance and that evolution of resistance requires (negative) linkage disequilibrium between the two loci. When the two loci are unlinked or only partially so, a suppression drive that causes limited inviability can evolve to fixation while causing only a minor increase in resistance frequency. Once fixed, the drive allele no longer selects resistance. Our analyses suggest that among gene drives that cause moderate suppression, toxin-antidote systems are less apt to select for resistance than homing drives. Single drives of moderate effect might cause only moderate population suppression, but multiple drives (perhaps delivered sequentially) would allow arbitrary levels of suppression. The most favorable case for evolution of resistance appears to be with suppression homing drives in which resistance is dominant and fully suppresses transmission distortion; partial suppression by resistance heterozygotes or recessive resistance are less prone to resistance evolution. Given that it is now possible to engineer CRISPR-based gene drives capable of circumventing allelic resistance, this design may allow for the engineering of suppression gene drives that are effectively resistance-proof.
登录
查看更多内容
DOI：
10.1126/science.aaa5945
发表时间：
2015-04-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gantz VM;Bier E
通讯作者：
Bier E
影响因子：
--
作者：
Gould, F;Magori, K;Huang, YX
通讯作者：
Huang, YX
DOI：
10.1098/rspb.2008.0846
发表时间：
2008-12-22
影响因子：
4.7
作者：
Gould, Fred;Huang, Yunxin;Lloyd, Alun L.
通讯作者：
Lloyd, Alun L.
影响因子：
1.4
作者：
Beaghton, Andrea;Beaghton, Pantelis John;Burt, Austin
通讯作者：
Burt, Austin
影响因子：
3.3
作者：
Gould, Fred
通讯作者：
Gould, Fred