Vector control with driving Y chromosomes: modelling the evolution of resistance
Vector control with driving Y chromosomes: modelling the evolution of resistance
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DOI：
10.1186/s12936-017-1932-7
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发表时间：
2017-07-14
期刊：
影响因子：
3
通讯作者：
Burt, Austin
中科院分区：
文献类型：
--
作者：
Beaghton, Andrea;Beaghton, Pantelis John;Burt, Austin
背景资料：采用新的疟疾控制干预措施往往导致寄生虫对新药和蚊媒对新杀虫剂产生抗药性，从而损害干预措施的效力。分子和种群生物学的最新进展提高了新的基于遗传的干预措施的可能性，应该考虑对这些措施的抗性演变的可能性。在这里，群体模型被用来确定影响对合成的、基于核酸酶的驱动Y染色体的抗性进化的可能性的主要因素，该Y染色体产生男性偏向的性别比例。结合确定性微分方程模型和随机分析，包括分支过程和吉莱斯皮模拟，用于评估阻力对驱动Y演变的概率，否则就足够强消灭目标人群该模型认为，由于在靶位点的变化，使它们不再被切割的核酸酶，并由于反式作用的常染色体抑制等位基因。结果：抗性进化的概率增加的突变率和人口的内在增长率，并减少与驱动器的强度和任何多效性的健身成本的抗性等位基因。在季节性变化的环境中，释放时间也会影响抗性进化的概率。反式作用的抑制等位基因更有可能遭受随机损失，在低频率比靶位点耐药allelease.Conclusions：与任何其他干预措施，有一个风险，抗性将演变成新的遗传方法，以载体控制，并应采取措施，尽量减少这种可能性。在这方面有两个设计特征应该有所帮助，一是降低耐药突变出现的速度，二是靶向序列，如果它们确实出现，它们会给蚊子带来显著的适应性成本。
Background: The introduction of new malaria control interventions has often led to the evolution of resistance, both of the parasite to new drugs and of the mosquito vector to new insecticides, compromising the efficacy of the interventions. Recent progress in molecular and population biology raises the possibility of new genetic-based interventions, and the potential for resistance to evolve against these should be considered. Here, population modelling is used to determine the main factors affecting the likelihood that resistance will evolve against a synthetic, nuclease-based driving Y chromosome that produces a male-biased sex ratio.Methods: A combination of deterministic differential equation models and stochastic analyses involving branching processes and Gillespie simulations is utilized to assess the probability that resistance evolves against a driving Y that otherwise is strong enough to eliminate the target population. The model considers resistance due to changes at the target site such that they are no longer cleaved by the nuclease, and due to trans-acting autosomal suppressor alleles.Results: The probability that resistance evolves increases with the mutation rate and the intrinsic rate of increase of the population, and decreases with the strength of drive and any pleiotropic fitness costs of the resistant allele. In seasonally varying environments, the time of release can also affect the probability of resistance evolving. Trans-acting suppressor alleles are more likely to suffer stochastic loss at low frequencies than target site resistant alleles.Conclusions: As with any other intervention, there is a risk that resistance will evolve to new genetic approaches to vector control, and steps should be taken to minimize this probability. Two design features that should help in this regard are to reduce the rate at which resistant mutations arise, and to target sequences such that if they do arise, they impose a significant fitness cost on the mosquito.