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

无性蛭形轮虫适应剧毒病原体的基因组基础

• 批准号: NE/S010866/1
• 负责人: Timothy Barraclough
• 金额: $ 66.71万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FS010866%2F1
• 关键词: genomic; basis; adaptation; virulent; pathogens

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.

对于科学家来说，性是一件令人尴尬的事情，因为它是一种如此低效的繁衍后代的方式，以至于简单的理论认为它根本不应该存在。从理论上讲，雌性动物可以通过产卵孵化成相同的克隆体来传递它们的基因，而不是让雄性贡献50%的DNA。一个全是女性的“无性”种群的增长速度可能是现在的两倍。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放在身边，或者花那么多的时间和精力在性上。这是自达尔文以来一直困扰生物学家的大问题之一。一个主要观点是克隆种群是由疾病导致灭绝的。如果个体在基因上是相同的，一种病原体进化后感染一个个体，就可以杀死所有个体。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抗不断变化的病原体。这个想法被称为“红皇后”假说（RQH），以爱丽丝梦游仙境中的一个角色命名，她必须一直跑来跑去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在不久之后消失，但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似乎打破所有规则的奇怪动物来回答这个问题。蛭形轮虫是一种微小的水生无脊椎动物，似乎在5000万年前就放弃了性生活，但在世界各地非常成功，有500多个物种。他们被称为“进化的丑闻”，因为性被认为是必不可少的。他们的成功对RQH来说是一个问题，因为他们受到讨厌的真菌病原体的攻击，这些病原体可以在短短几周内消灭种群。为什么它们没有灭绝？如果RQH是正确的，那么蛭类动物一定有不同寻常的替代策略来科普疾病。我们将研究两种可能性：（1）蛭形类可能使用以前未知的遗传技巧来改组它们的免疫防御。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是由特殊的过程驱动的，比如奇怪的性行为，或者是一种奇怪的机制，让它们从其他生物体中获得DNA。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“跑”，以在遗传上跟上病原体。如果我们找不到这样的机制，即使是免疫基因，这将证实蛭形动物缺乏遗传改组。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，甚至可能找到可能对真菌有用的抗菌剂。(2)蛭形轮虫的生态和生活方式可能会让它们逃离病原体。蛭形轮虫在苔藓和雨水的临时补丁中茁壮成长，并具有完全干燥的生存能力。它们形成灰尘状的颗粒，可以被风带到几英里外，但真菌无法在这个过程中生存。也许轮虫在苔藓斑块中分散的频率太高，以至于病原体无法跟上，所以蛭形轮虫通过分散而不是遗传洗牌“逃跑”。为了验证这一假设，我们将跟踪苔藓中轮虫基因型随时间的变化，看看外来动物是否更善于抵抗疾病。如果蛭形动物与病原体玩生态学上的“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通过显示蛭形动物如何逃避疾病和灭绝来支持RQH。这将解决一个“进化丑闻”，并有助于解释为什么性是如此普遍。但是，如果我们发现蛭形类动物在没有奇怪的遗传或生态技巧的情况下蓬勃发展，这将意味着疾病对长期克隆谱系的威胁被夸大了，这将导致对性别尴尬问题的重大反思。

项目成果

Comparative genomics of Alexander Fleming's original Penicillium isolate (IMI 15378) reveals sequence divergence of penicillin synthesis genes

亚历山大·弗莱明 (Alexander Fleming) 的原始青霉菌分离株 (IMI 15378) 的比较基因组学揭示了青霉素合成基因的序列差异

• DOI: 10.3929/ethz-b-000478567
• 发表时间: 2020
• 作者: Pathak, Ayush

Historical genomics reveals the evolutionary mechanisms behind multiple outbreaks of the host-specific coffee wilt pathogen Fusarium xylarioides.

• DOI: 10.1186/s12864-021-07700-4
• 发表时间: 2021-06-04
• 期刊: BMC genomics
• 影响因子: 4.4
• 作者: Peck LD;Nowell RW;Flood J;Ryan MJ;Barraclough TG
• 通讯作者: Barraclough TG

Comparative genomics of Alexander Fleming's original Penicillium isolate (IMI 15378) reveals sequence divergence of penicillin synthesis genes.

• DOI: 10.1038/s41598-020-72584-5
• 发表时间: 2020-09-24
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Pathak A;Nowell RW;Wilson CG;Ryan MJ;Barraclough TG
• 通讯作者: Barraclough TG

Evolutionary dynamics of transposable elements in bdelloid rotifers.

• DOI: 10.7554/elife.63194
• 发表时间: 2021-02-05
• 期刊: eLife
• 影响因子: 7.7
• 作者: Nowell RW;Wilson CG;Almeida P;Schiffer PH;Fontaneto D;Becks L;Rodriguez F;Arkhipova IR;Barraclough TG
• 通讯作者: Barraclough TG

Whole-genome analyses converge to support the Hemirotifera hypothesis within Syndermata (Gnathifera)

• DOI: 10.1007/s10750-023-05451-9
• 发表时间: 2024-01-18
• 期刊: HYDROBIOLOGIA
• 影响因子: 2.6
• 作者: Vasilikopoulos，Alexandros;Herlyn，Holger;Van Doninck，Karine
• 通讯作者: Van Doninck，Karine