Bull James J
Department of Integrative Biology, University of Texas, Austin, TX, USA
Institute of Cellular and Molecular Biology, University of Texas, Austin, TX, USA.
Evol Med Public Health. 2016 Dec;2017(1):1-16. doi: 10.1093/emph/eow030. Epub 2016 Nov 8.
The use of 'selfish' gene drive systems to suppress or even extinguish populations has been proposed on theoretical grounds for almost half a century. Creating these genes has recently become possible with CRISPR technology. One seemingly feasible approach, originally proposed by Burt, is to create a homing endonuclease gene (HEG) that inserts into an essential gene, enabling heterozygote viability but causing homozygote lethality. With 100% segregation distortion in gametes, such genes can cause profound population suppression if resistance does not evolve. Here, population genetic models are used to consider the evolution of inbreeding (specifically selfing) as a possible response to a recessively lethal HEG with complete segregation distortion. Numerical analyses indicate a rich set of outcomes, but selfing often evolves in response to the HEG, with a corresponding partial restoration of mean fitness. Whether selfing does indeed evolve and its effect in restoring fitness depends heavily on the magnitude of inbreeding depression. Overall, these results point toward an underappreciated evolutionary response to block the harmful effects of a selfish gene. They raise the possibility that extreme population suppression may be resisted by mechanisms that are independent of the molecular basis of gene drive. At the same time, the evolution of inbreeding is not assured even if the genetic basis for inbreeding is present. As the models here strictly apply to hermaphrodites (plants), an important next step is to consider inbreeding in populations with separate sexes.
基于理论依据，利用“自私”基因驱动系统抑制甚至消灭种群的提议已存在了近半个世纪。借助CRISPR技术，如今已能够创造出这类基因。一种最初由伯特提出的看似可行的方法，是创造一种归巢内切酶基因（HEG），该基因插入一个必需基因中，使杂合子具有生存能力，但导致纯合子致死。由于配子中100%的分离畸变，若抗性不进化，此类基因可导致种群受到严重抑制。在此，种群遗传模型被用于研究近亲繁殖（具体为自交）的进化，作为对具有完全分离畸变的隐性致死HEG的一种可能反应。数值分析表明存在一系列丰富的结果，但自交往往会因HEG而进化，同时平均适合度会相应部分恢复。自交是否真的会进化及其对适合度恢复的影响在很大程度上取决于近亲繁殖衰退的程度。总体而言，这些结果指向一种未得到充分认识的进化反应，以阻止自私基因的有害影响。它们提出了一种可能性，即极端的种群抑制可能会被独立于基因驱动分子基础的机制所抵抗。与此同时，即使存在近亲繁殖的遗传基础，近亲繁殖的进化也并非必然。由于这里的模型严格适用于雌雄同体（植物），下一步重要的是考虑在雌雄异体的种群中的近亲繁殖情况。
