Recent research shows that genetic selection has high potential to reduce the prevalence of infectious diseases in livestock. However, like all interventions that target infectious diseases, genetic selection of livestock can exert selection pressure on pathogen populations. Such selection on the pathogen may lead to escape strategies and reduce the effect of selection of livestock for disease resistance. Thus, to successfully breed livestock for lower disease prevalence, it is essential to develop strategies that prevent the invasion of pathogen mutants that escape host resistance. Here we investigate the conditions under which such “escape mutants” can replace wild-type pathogens in a closed livestock population using a mathematical model of disease transmission. Assuming a single gene that confers sufficient resistance, results show that genetic selection for resistance in livestock typically leads to an “invasion window” within which an escape mutant of the pathogen can invade. The bounds of the invasion window are determined by the frequency of resistant hosts in the population. The lower bound occurs when the escape mutant has an advantage over the wild-type pathogen in the population. The upper bound occurs when local eradication of the pathogen is expected. The invasion window is smallest when host resistance is strong and when infection with the wild-type pathogen provides cross immunity to infection with the escape mutant. To minimise opportunities for pathogens to adapt, under the assumptions of our model, the aim of disease control through genetic selection should be to achieve herd-level eradication of the infection faster than the rate of emergence of escape mutants of the pathogen. Especially for microparasitic infections, this could be achieved by placing animals into herds according to their genetic resistance, such that these herds stay completely out of the invasion window. In contrast to classical breeding theory, our model suggests that multi-trait selection with gradual improvement of each trait of the breeding goal might not be the best strategy when resistance to infectious disease is part of the breeding goal. Temporally, combining genetic selection with other interventions helps to make the invasion window smaller, and thereby reduces the risk of invasion of escape mutants.

中文翻译：

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育种者在选择增加对传染病的抵抗力时能否阻止病原体适应？

最近的研究表明，遗传选择在降低牲畜传染病流行方面具有很大潜力。然而，与所有针对传染病的干预措施一样，家畜的遗传选择会对病原体种群施加选择压力。这种对病原体的选择可能会导致逃避策略，并降低牲畜抗病性选择的效果。因此，为了成功培育牲畜以降低疾病流行率，必须制定策略来防止逃避宿主抵抗力的病原体突变体入侵。在这里，我们使用疾病传播的数学模型研究这种“逃逸突变体”可以在封闭的牲畜种群中取代野生型病原体的条件。假设单个基因具有足够的抗性，结果表明，针对家畜抗性的遗传选择通常会导致一个“入侵窗口”，病原体的逃逸突变体可以在该窗口内入侵。入侵窗口的界限由种群中耐药宿主的频率决定。当逃逸突变体比种群中的野生型病原体具有优势时，就会出现下限。当预期局部根除病原体时出现上限。当宿主抵抗力强并且野生型病原体感染提供对逃逸突变体感染的交叉免疫时，入侵窗口最小。为了尽量减少病原体适应的机会，在我们模型的假设下，通过基因选择控制疾病的目的应该是在畜群层面根除感染，速度要快于病原体逃逸突变体出现的速度。特别是对于微寄生虫感染，这可以通过根据动物的遗传抗性将动物分入畜群来实现，这样这些畜群就可以完全远离入侵窗口。与经典育种理论相反，我们的模型表明，当抗传染病是育种目标的一部分时，逐步改进育种目标的每个性状的多性状选择可能不是最佳策略。在时间上，将遗传选择与其他干预相结合有助于使入侵窗口更小，从而降低逃逸突变体入侵的风险。特别是对于微寄生虫感染，这可以通过根据动物的遗传抗性将动物分入畜群来实现，这样这些畜群就可以完全远离入侵窗口。与经典育种理论相反，我们的模型表明，当抗传染病是育种目标的一部分时，逐步改进育种目标的每个性状的多性状选择可能不是最佳策略。在时间上，将遗传选择与其他干预相结合有助于使入侵窗口更小，从而降低逃逸突变体入侵的风险。特别是对于微寄生虫感染，这可以通过根据动物的遗传抗性将动物分入畜群来实现，这样这些畜群就可以完全远离入侵窗口。与经典育种理论相反，我们的模型表明，当抗传染病是育种目标的一部分时，逐步改进育种目标的每个性状的多性状选择可能不是最佳策略。在时间上，将遗传选择与其他干预相结合有助于使入侵窗口更小，从而降低逃逸突变体入侵的风险。我们的模型表明，当抗传染病是育种目标的一部分时，通过逐步改进育种目标的每个性状进行多性状选择可能不是最佳策略。在时间上，将遗传选择与其他干预相结合有助于使入侵窗口更小，从而降低逃逸突变体入侵的风险。我们的模型表明，当抗传染病是育种目标的一部分时，通过逐步改进育种目标的每个性状进行多性状选择可能不是最佳策略。在时间上，将遗传选择与其他干预相结合有助于使入侵窗口更小，从而降低逃逸突变体入侵的风险。