Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK.
Department of Life Sciences, Imperial College London, Silwood Park, Ascot, Berkshire, SL5 7PY, UK.
BMC Biol. 2017 Sep 11;15(1):81. doi: 10.1186/s12915-017-0420-4.
Driving endonuclease genes (DEGs) spread through a population by a non-Mendelian mechanism. In a heterozygote, the protein encoded by a DEG causes a double-strand break in the homologous chromosome opposite to where its gene is inserted and when the break is repaired using the homologue as a template the DEG heterozygote is converted to a homozygote. Some DEGs occur naturally while several classes of endonucleases can be engineered to spread in this way, with CRISPR-Cas9 based systems being particularly flexible. There is great interest in using driving endonuclease genes to impose a genetic load on insects that vector diseases or are economic pests to reduce their population density, or to introduce a beneficial gene such as one that might interrupt disease transmission. This paper reviews both the population genetics and population dynamics of DEGs. It summarises the theory that guides the design of DEG constructs intended to perform different functions. It also reviews the studies that have explored the likelihood of resistance to DEG phenotypes arising, and how this risk may be reduced. The review is intended for a general audience and mathematical details are kept to a minimum.
驱动核酸内切酶基因（DEGs）通过非孟德尔机制在种群中传播。在杂合子中，由 DEG 编码的蛋白质会在与其基因插入位置相对的同源染色体上造成双链断裂，当使用同源物作为模板修复断裂时，DEG 杂合子就会转化为纯合子。一些 DEGs 是自然发生的，而几类内切核酸酶可以通过这种方式进行工程设计，基于 CRISPR-Cas9 的系统尤其灵活。人们对利用驱动核酸内切酶基因对传播疾病或对经济有害的昆虫施加遗传负荷以降低其种群密度，或引入有益基因（如可能中断疾病传播的基因）非常感兴趣。本文综述了 DEGs 的群体遗传学和种群动态。它总结了指导旨在发挥不同功能的 DEG 构建体设计的理论。它还回顾了探索对 DEG 表型产生抗性的可能性的研究，以及如何降低这种风险。本文面向一般读者，尽量减少数学细节。
