Suppr超能文献

控制归巢基因驱动的频率动态以实现中间结果。

Controlling the frequency dynamics of homing gene drives for intermediate outcomes.

作者信息

Camm Benjamin J, Fournier-Level Alexandre

机构信息

School of BioSciences, The University of Melbourne, Parkville, VIC 3010, Australia.

出版信息

G3 (Bethesda). 2025 Feb 5;15(2). doi: 10.1093/g3journal/jkae300.

Abstract

Gene drives have enormous potential for solving biological issues by forcing the spread of desired alleles through populations. However, to safeguard from the potentially irreversible consequences on natural populations, gene drives with intermediate outcomes that neither fixate nor get removed from the population are of outstanding interest. To elucidate the conditions leading to intermediate gene drive outcomes, a stochastic, individual allele-focused gene drive model was developed to simulate the diffusion of a homing gene drive in a population. The frequencies of multiple alleles at a locus targeted by a gene drive were tracked under various scenarios. These explored the effect of gene drive conversion efficiency, strength and frequency of resistance alleles, dominance and strength of a fitness cost for the gene drive, and the level of inbreeding. Four outcomes were consistently observed: fixation, loss, temporary, and equilibrium. The latter 2 are defined by the frequency of the gene drive peaking then crashing or plateauing, respectively. No single variable determined the outcome of a drive. The difference between the conversion efficiency and resistance level, modeled quantitatively, differentiated the temporary and equilibrium outcomes. The frequency dynamics of the gene drive within outcomes varied extensively, with different variables driving these dynamics between outcomes. These simulation results highlight the possibility of fine-tuning gene drive outcomes and frequency dynamics. To that end, we provide a web application implementing our model, which will guide the safer design of gene drives able to achieve a range of controllable outcomes tailored to population management needs.

摘要

基因驱动通过促使所需等位基因在种群中传播,在解决生物学问题方面具有巨大潜力。然而,为了防范对自然种群可能产生的不可逆转的后果,具有既不固定也不从种群中消除的中间结果的基因驱动备受关注。为了阐明导致基因驱动产生中间结果的条件,开发了一个随机的、以单个等位基因为重点的基因驱动模型,以模拟归巢基因驱动在种群中的扩散。在各种情况下跟踪基因驱动靶向位点上多个等位基因的频率。这些情况探讨了基因驱动转换效率、抗性等位基因的强度和频率、基因驱动适应度代价的显性和强度以及近亲繁殖水平的影响。一致观察到四种结果:固定、丢失、暂时和平衡。后两种结果分别由基因驱动频率达到峰值后崩溃或趋于平稳来定义。没有单一变量能决定基因驱动的结果。通过定量建模,转换效率和抗性水平之间的差异区分了暂时和平衡结果。基因驱动在结果中的频率动态变化很大,不同变量在不同结果之间驱动这些动态变化。这些模拟结果凸显了微调基因驱动结果和频率动态的可能性。为此,我们提供了一个实现我们模型的网络应用程序,它将指导更安全地设计基因驱动,以实现一系列根据种群管理需求定制的可控结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73be/11797013/8b166378bfc8/jkae300f1.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验