发表机构
University of Texas at San Antonio（圣安东尼奥德克萨斯大学）
机构由 AI 辅助整理，请以论文原文为准。AI 中文总结
本研究建立埃及伊蚊中 Medea 基因驱动的连续时间模型，分析其平衡点、稳定性及双稳态释放阈值，并通过敏感性分析和分批释放模拟，为野外种群替换提供策略指导。
AI 中文摘要
蚊媒疾病如登革热、寨卡和黃热病给全球健康带来沉重负担，这促使人们采用遗传控制策略，用对疾病具有抵抗力的野生蚊群替换易感蚊群。母性效应显性胚胎停滞（Medea）是一种基因驱动，携带 Medea 等位基因的母体所产后代除非继承该等位基因，否则会死亡，从而产生偏向性遗传，能够将连锁的抗病性状推向高频率。我们开发并分析了一个埃及伊蚊中 Medea 动态的连续时间分室模型，该模型按生命阶段和基因型追踪蚊子丰度，并推广了驱动机制，允许不完美的 Medea 杀伤和不完美的救援。我们刻画了生物学相关的平衡点并推导了其局部稳定性条件，以及基因型特异的繁殖数和控制低频入侵的基本繁殖数（R0）。分岔分析揭示了双稳态性，因此存在一个必须超过的释放阈值，Medea 才能占据主导，尽管基线时 R0<1。不完美的杀伤和不完美的救援以不同方式重塑了这一分岔结构：杀伤泄漏控制入侵阈值，而救援效率控制所得种群的组成。敏感性分析确定适合度系数和杀伤泄漏是阈值和覆盖结果的主要驱动因素，蚊子种群参数影响绝对丰度但不影响基因型比例。分批释放计划的模拟为有效的野外部署提供信息，并表明逆转已建立的驱动比实现正向入侵成本高得多，尽管同时释放两性加速逆转的程度远大于加速入侵。
英文摘要
Mosquito-borne diseases such as dengue, Zika, and yellow fever impose a substantial global health burden, motivating genetic control strategies that replace wild mosquito populations with disease-refractory ones. Maternal-effect dominant embryonic arrest (Medea) is a gene drive in which the offspring of a Medea-carrying mother die unless they inherit the Medea allele, producing biased inheritance capable of driving a linked refractory trait to high prevalence. We develop and analyze a continuous-time compartmental model of Medea dynamics in Aedes aegypti that tracks mosquito abundance by life stage and genotype, and that generalizes the drive mechanism to allow both imperfect Medea-killing and imperfect rescue. We characterize the biologically relevant equilibria and derive their local stability conditions, together with genotype-specific reproduction numbers and the basic reproduction number (R0) governing invasion from low frequency. Bifurcation analysis reveals bistability, and hence a release threshold that must be exceeded for Medea to take over, even though R0<1 at baseline. Imperfect killing and imperfect rescue reshape this bifurcation structure in distinct ways: killing leakage governs the invasion threshold, while rescue efficiency governs the composition of the resulting population. Sensitivity analysis identifies the fitness coefficient and killing leakage as the dominant drivers of both threshold and coverage outcomes, with mosquito demographic parameters affecting absolute abundances but not genotype proportions. Simulations of batched release programs inform efficient field deployment and show that reversing an established drive is substantially more costly than achieving forward invasion, though co-releasing both sexes accelerates reversal considerably more than it accelerates invasion.
