The life cycles of parasitic worms, from macroevolutionary patterns to the genetics of adaptation

许多寄生虫有复杂的生命周期，它们在繁殖之前会连续感染多个宿主。这些生命周期令人困惑，因为它们看起来很危险。随着生命周期中连续主机数量的增加，无法到达下一个主机从而无法完成周期的风险也会增加。此外，这些寄生虫必须适应不同的宿主生理、免疫系统和通常的热状态（例如，从冷血宿主转移到温血宿主时）。在多种寄生虫分类群中，复杂生命周期的进化和持续存在的抵消效益是什么？又是什么基因变化造就了这样的生活方式？为了解决这些问题，我提出了两种互补的项目：(I)跨物种比较分析和（ii）基因组和转录组比较。我编制了一个寄生虫生命周期的综合数据库，其中包括近1000种寄生虫。我将使用这个数据库来检验关于生命周期进化的假设，例如复杂的生命周期寄生虫是否会长得更大或感染更多种类的宿主。这些分析将确定简单周期和复杂周期寄生虫之间的关键区别。然后，我建议探索这些差异如何在寄生虫基因组中表现出来。我将使用现有的数据集来寻找独立谱系中共享的基因组特征，如基因家族扩展或选择性剪接的增加，这将表明复杂生命周期所带来的问题的一般解决方案。我还描述了转录组学实验，评估不同宿主的寄生虫阶段在何时以及在多大程度上是遗传“解耦”的，即影响一个宿主的一个阶段的遗传变化是否对其他宿主的阶段产生相关影响。通过结合表型、基因组和转录组学方法，我希望揭示复杂生命周期进化的原因（成本和收益）和方式（适应的遗传机制）。

Many parasites have complex life cycles in which they infect multiple hosts in succession before reproducing. These life cycles are perplexing, because they seem risky. As the number of consecutive hosts in a life cycle increases, so does the risk of not making it to the next host and thus not completing the cycle. Additionally, such parasites must adapt to different host physiologies, immune systems, and often thermal regimes (e.g. when moving from cold- to warm-blooded hosts). What are the offsetting benefits that explain the evolution and persistence of complex life cycles in multiple parasite taxa? And what genetic changes enable such a life style? To address these questions, I propose two complementary kinds of projects: (i) cross-species comparative analyses and (ii) genomic and transcriptomic comparisons. I have compiled a comprehensive database of parasitic worm life cycles that includes nearly 1000 species. I will use this database to test hypotheses about life cycle evolution, such as whether complex life cycle parasites grow larger or infect a wider variety of hosts. These analyses will identify key differences between simple- and complex-cycle parasites. I then propose exploring how such differences are manifested in parasite genomes. I will use existing datasets to look for shared genomic features in independent lineages, like gene family expansions or increases in alternative splicing, that would be indicative of general solutions to the problems posed by complex life cycles. I also describe transcriptomic experiments assessing when and to what extent parasite stages in different hosts are genetically ‘decoupled’, i.e. whether genetic changes affecting a stage in one host have correlated effects on stages in other hosts. By combining phenotypic, genomic, and transcriptomic approaches, I hope to reveal both why (the costs and benefits) and how (the genetic mechanisms of adaptation) complex life cycles have evolved.