Evolution of parasite reproductive strategies in natural infections

预测寄生虫如何适应环境变得越来越重要。例如，气候、宿主-寄生虫-病媒群落组成和生境的变化与野生动物、作物物种、牲畜和人类出现新的传染病有关。更广泛地说，寄生虫所经历的宿主内环境也变化迅速而广泛。了解寄生虫如何应对宿主内多变的环境是理解疾病和传染性的核心，也为预测寄生虫对其生态环境的其他变化的进化提供了一个框架。我们将使用进化理论来提出进化生物学和传染病研究中的基本问题：原生动物寄生虫的繁殖（传播）策略是如何进化的？这类寄生虫包括疟疾（疟原虫）寄生虫，是家畜、伴侣动物、野生动物和人类的一些最严重病原体。尽管了解疟疾寄生虫的传播策略在经济、医学和兽医方面具有重要意义，但一个多世纪的研究对它们的基本生殖生物学知之甚少。然而，近年来取得了快速进展：新的分子工具已经开发出来，并在进化框架中应用，以询问有关寄生虫传播的问题。从寄生虫的流行病学到它们在感染期间的行为，这种新方法的数据正在颠覆传统的智慧。例如，我们发现寄生虫以非常复杂的方式微调传播阶段的产量和性别比例；根据它们在宿主内的密度，与其他寄生虫菌株的竞争，以及它们的宿主是否贫血，是否产生免疫反应，或是否接受药物治疗。这些“塑料计划生育策略”使寄生虫能够通过使它们的行为与它们在感染期间面临的不断变化的条件相匹配，从而最大限度地传播。然而，这些研究集中在实验室实验中的模式寄生虫上——这些“复杂”策略是否发生在自然感染中是有争议的。我们将通过开发敏感的方法来量化人类疟疾（恶性疟原虫）寄生虫在野外传播（繁殖）阶段的产量和性别比例，并测试进化理论是否可以解释它们的策略来解决这个问题。我们已经为一种相关的疟疾寄生虫开发了这些方法，并为将这种方法转化为人类寄生虫奠定了基础。进化理论预测，寄生虫的繁殖策略将由它们在感染期间遇到的宿主环境的变化而形成。大多数关于寄生虫传播的研究都集中在传播阶段的数量或性别比例上，但是进化理论预测这些特征是同时优化的——因此它们需要一起研究，而且只能在彼此的背景下才能理解。解释个体表现出的生活史特征的变异是进化生物学的一个主要目标。人们对使用进化方法来了解寄生虫生活史特征如何在感染动力学中形成并促进毒力和传播也越来越感兴趣。鉴于最近在实验室实验中观察到的复杂的寄生虫策略，研究寄生虫在自然感染中的行为是及时和重要的。了解寄生虫繁殖策略的可塑性对于预测它们对生态变化的短期和长期反应也至关重要，例如栖息地的变化、宿主的转移或控制措施如何影响疾病的传播。

Predicting how parasites adapt to their environment is becoming increasingly important. For example, changes to: the climate, composition of host-parasite-vector communities, and habitat, are implicated in the emergence of new infectious diseases of wildlife, crop species, livestock, and humans. More broadly, the in-host environment experienced by parasites also varies rapidly and extensively. Understanding how parasites cope with a variable in-host environment is central to understanding disease and infectiousness, as well as providing a framework for predicting parasite evolution in response to other changes in their ecology. We will use evolutionary theory to ask fundamental questions in evolutionary biology and infectious disease research: how do reproductive (transmission) strategies of protozoan parasites evolve? This group includes malaria (Plasmodium) parasites and cause some of the most serious pathogens of livestock, companion animals, wildlife, and humans. Despite the economic, medical, and veterinary importance of understanding the transmission strategies of malaria parasites, over a century of research has yielded remarkably little understanding of their basic reproductive biology. However, rapid progress has been made in recent years: new molecular tools have been developed and applied in an evolutionary framework to ask questions about parasite transmission. Data from this new approach are overturning the conventional wisdom: from the epidemiology of parasites to their behaviour during infections. For example, we have discovered that parasites fine-tune the production and sex ratio of transmission stages in remarkably sophisticated ways; according to their density within hosts, competition with other parasite strains, and whether their hosts are anaemic, mounting an immune response, or receiving drug treatment. These 'plastic family planning strategies' enable parasites to maximise transmission by matching their behaviour to the changing conditions they face during infections. However, these studies have focused on model parasites in laboratory experiments - whether these 'sophisticated' strategies occur in natural infections is controversial. We will address this by developing sensitive methods to quantify the production and sex ratio of transmission (reproductive) stages of human malaria (P. falciparum) parasites in the wild and testing whether evolutionary theory can explain their strategies. We have already developed these methods for a related species of malaria parasite and laid the groundwork for translating this assay to human parasites. Evolutionary theory predicts that parasite reproductive strategies will be shaped by the variation in their in-host environment that they encounter during infections. Most studies on parasite transmission have focused on either the number or sex ratio of transmission stages but evolutionary theory predicts these traits are simultaneously optimised - therefore they need to be investigated together and can only be understood in the context of each other. Explaining variation in the life-history traits exhibited by individuals is a major aim in evolutionary biology. There is also increasing interest in using an evolutionary approach to understand how parasite life-history traits shape within-infection dynamics and contribute to virulence and transmission. Given the sophisticated parasite strategies recently observed in lab experiments, investigating the behaviour of parasites in natural infections is timely and important. Understanding plasticity in the reproductive strategies of parasites is also central to predicting their short- and long-term responses to changes in their ecology: such as how habitat change, host shifts, or control measures influence the spread of disease.