The genomic basis of adaptation to virulent pathogens in asexual bdelloid rotifers

性行为让科学家们感到尴尬，因为它是一种低效的繁殖后代的方式，简单的理论认为它根本不应该存在。从理论上讲，雌性动物通过产卵孵化出完全相同的克隆体，而不是让雄性贡献50%的DNA，从而将自己的基因传递下去，其效率是雌性动物的两倍。全雌性“无性”种群的增长速度是其两倍。有了这个巨大的优势，很难理解为什么几乎所有的植物和动物都把雄性留在身边，或者花那么多时间和精力进行交配。这是自达尔文以来一直困扰生物学家的大问题之一。一种主流观点认为，无性繁殖种群是由疾病导致灭绝的。如果个体在基因上是相同的，一种病原体进化到感染一个人就能杀死他们所有人。性不断地打乱DNA，并将遗传多样性引入免疫系统。这有助于每一代人抵御不断变化的病原体。这个想法被称为“红皇后”假说（RQH），来自《爱丽丝梦游仙境》中的一个角色，她必须一直奔跑才能呆在同一个地方。完全放弃性行为的动物群体几乎总是很快消失，但尚不清楚这是由于疾病还是其他原因。我们计划通过调查一群奇怪的动物来回答这个问题，它们似乎打破了所有的规则。蛭形轮虫是一种微小的水生无脊椎动物，它们似乎在5000万年前就放弃了性生活，但在世界各地都非常成功，有500多种。它们被称为“进化丑闻”，因为性被认为是不可或缺的。它们的成功对RQH来说是一个问题，因为它们受到令人讨厌的真菌病原体的攻击，这些病原体可以在几周内消灭种群。为什么它们还没有灭绝？如果RQH是正确的，那么蛭状细胞一定有不同寻常的替代策略来应对疾病。我们将研究两种可能性：(1)蛭形虫可能使用以前未知的遗传技巧来洗牌它们的免疫防御。利用基因组测序技术，我们将确定保护轮虫免受真菌攻击的基因和蛋白质。我们会问，这些免疫基因的变异是否受到特殊过程的驱动，比如奇怪的性行为形式，或者是一种让它们从其他生物体中获取DNA的奇怪机制。这两种观点的证据都支持RQH的预测，即即使是蛭形轮虫也需要尽可能快地“奔跑”，以跟上病原体的基因。如果我们没有发现这样的机制，即使是免疫基因，它将证实蛭形蛋白缺乏遗传洗牌。无论哪种情况，我们都将获得关于动物如何抵抗疾病的新见解，甚至可能发现可能对真菌有用的抗菌剂。(2)蛭形虫的生态环境和生活方式可能使其逃避病原体。蛭形虫在苔藓和雨水的临时斑块中茁壮成长，并且具有完全干燥的生存能力。它们形成类似尘埃的颗粒，可以被风带到几英里外，但真菌无法在这个过程中存活下来。也许轮虫经常分散在苔藓斑块中，以至于病原体无法在物理上跟上，因此轮虫通过分散而不是基因重组来“逃跑”。为了测试这种情况，我们将跟踪苔藓中轮虫基因型随时间的变化，并观察进入的动物是否更能抵抗疾病。如果蛭形虫正在与病原体玩生态“捉迷藏”，这将再次表明，需要特殊的机制来取代性。一种或两种可能性的证据将支持RQH，表明蛭形体如何逃脱疾病和灭绝。这将解决“进化丑闻”，并有助于解释为什么性行为如此普遍。但是，如果我们发现蛭形虫在没有奇怪的遗传或生态技巧的情况下茁壮成长，这将意味着疾病对长期克隆谱系的威胁被夸大了，这将导致人们对令人尴尬的性问题进行实质性的反思。

Sex is embarrassing for scientists, because it is such an inefficient way to make offspring that simple theory says it should not exist at all. In theory, female animals could pass on their genes twice as effectively by making eggs that hatch into identical clones, rather than letting males contribute 50% of the DNA. An all-female 'asexual' population could grow twice as quickly. With this huge advantage, it is hard to see why nearly all plants and animals keep males around, or spend so much time and energy on sex. This is one of the Big Questions that has puzzled biologists since Darwin. One leading idea is that clonal populations are driven extinct by diseases. If individuals are genetically identical, a pathogen that evolves to infect one can kill them all. Sex continually shuffles DNA and introduces genetic diversity to the immune system. This helps each new generation to resist the ever-changing pathogens. This idea is called the 'Red Queen' hypothesis (RQH), after a character from Alice in Wonderland who had to run all the time to stay in the same place. Animal groups that completely abandon sex almost always vanish soon afterwards, but it is not clear if this is due to diseases or something else. We plan to answer this by investigating a strange group of animals that seem to break all the rules. Bdelloid rotifers are tiny aquatic invertebrates that seemingly abandoned sex over 50 million years ago, but are highly successful all over the world, with more than 500 species. They have been called 'an evolutionary scandal' because sex is supposed to be indispensable. Their success is a problem for the RQH, as they are attacked by nasty fungal pathogens that can exterminate populations in just a few weeks. Why haven't they gone extinct? If the RQH is right, bdelloids must have unusual alternative strategies to cope with diseases. We will investigate two possibilities: (1) Bdelloids might use previously unknown genetic tricks to shuffle their immune defences. Using genome sequencing technology, we will identify the genes and proteins that protect rotifers from fungal attack. We will ask whether variation in these immunity genes is driven by special processes, like odd forms of sex, or a weird mechanism that lets them pick up DNA from other organisms. Evidence for either idea would support the RQH's prediction that even bdelloid rotifers need to 'run' as fast as they can to keep up with pathogens genetically. If we find no such mechanisms, even for immune genes, it would confirm that bdelloids lack genetic shuffling. In either case, we will gain new insights about how animals resist diseases, and perhaps even find antimicrobials that might be useful against fungi. (2) Bdelloids' ecology and lifestyle might let them escape from pathogens. Bdelloids thrive in temporary patches of moss and rainwater, and have the unusual ability to survive complete desiccation. They form dust-like particles that can be carried by wind for miles, but the fungi cannot survive this process. Perhaps the rotifers disperse among moss patches so often that the pathogens cannot physically keep up, so that the bdelloids 'run away' by dispersal instead of genetic shuffling. To test this scenario we will track changes in rotifer genotypes in moss over time, and see whether incoming animals are better at resisting diseases. If bdelloids are playing ecological "hide-and-seek" with pathogens, it would again show that special mechanisms are needed to replace sex. Evidence for one or both possibilities would support the RQH by showing how bdelloids escape disease and extinction. It would solve an 'evolutionary scandal' and help explain why sex is so common. But, if we find that bdelloids are thriving without odd genetic or ecological tricks, it would imply that the threat of disease to long-term clonal lineages has been overstated, which would lead to a substantial rethink about the embarrassing problem of sex.