Modeling the mutation and reversal of engineered underdominance gene drives
Modeling the mutation and reversal of engineered underdominance gene drives
复制标题
DOI：
10.1016/j.jtbi.2019.06.024
复制
发表时间：
2019-10-21
影响因子：
2
通讯作者：
Alphey, Luke S.
中科院分区：
文献类型：
--
作者：
Edgington, Matthew P.;Alphey, Luke S.
已经提出了一系列的基因驱动系统，预计将增加其频率和相关的期望的遗传物质，即使他们赋予携带它们的个人的健身成本。工程化的欠显性（UD）是这样的系统，并且在一个版本中，是基于引入两个独立分离的转基因构建体，每个构建体携带致死基因、在另一个基因座处的致死基因的抑制子和期望的遗传“货物”。在该系统下，携带每种构建体的至少一个拷贝（或没有拷贝）的个体是有活力的，而仅具有一种转基因构建体的个体是无活力的。以前的理论工作已经探索了这些系统的各种特性，得出的结论是，它们应该在没有抗性或突变的情况下无限期地存在。在这里，我们研究了UD基因驱动的群体遗传学模型，该模型通过允许每个引入基因中的功能丧失突变来放松过去的假设。我们证明，突变很可能导致UD系统崩溃，最终导致消除引入的转基因。然后，我们继续研究释放携带“游离抑制因子”的个体作为逆转UD基因驱动的新方法的潜力，并将其与野生型的释放进行比较;这是先前唯一提出的UD逆转策略。这表明，虽然携带游离抑制子的个体可能代表一种廉价的逆转策略，但由于释放要求极小，它们不能像释放野生型那样迅速地返回完全野生型群体。(C)2019年，任作家。由爱思唯尔有限公司发布
A range of gene drive systems have been proposed that are predicted to increase their frequency and that of associated desirable genetic material even if they confer a fitness cost on individuals carrying them. Engineered underdominance (UD) is such a system and, in one version, is based on the introduction of two independently segregating transgenic constructs each carrying a lethal gene, a suppressor for the lethal at the other locus and a desirable genetic "cargo". Under this system individuals carrying at least one copy of each construct (or no copies of either) are viable whilst those that possess just one of the transgenic constructs are non-viable. Previous theoretical work has explored various properties of these systems, concluding that they should persist indefinitely in absence of resistance or mutation. Here we study a population genetics model of UD gene drive that relaxes past assumptions by allowing for loss-of-function mutations in each introduced gene. We demonstrate that mutations are likely to cause UD systems to break down, eventually resulting in the elimination of introduced transgenes. We then go on to investigate the potential of releasing "free suppressor" carrying individuals as a new method for reversing UD gene drives and compare this to the release of wild-types; the only previously proposed reversal strategy for UD. This reveals that while free suppressor carrying individuals may represent an inexpensive reversal strategy due to extremely small release requirements, they are not able to return a fully wild-type population as rapidly as the release of wild-types. (C) 2019 The Authors. Published by Elsevier Ltd.