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，在繁殖之前，它们会接连感染多个宿主。这些生命周期令人费解，因为它们似乎存在风险。随着生命周期中连续主机数量的增加，无法到达下一台主机从而无法完成周期的风险也会增加。此外，这种寄生虫必须适应不同的宿主生理、免疫系统，并经常适应热环境(例如，从冷血宿主迁移到温血宿主时)。解释多个寄生虫类群中复杂生命周期的进化和持久性的抵消好处是什么？是什么基因变化使这种生活方式成为可能呢？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。我编制了一个全面的寄生虫生命周期数据库，其中包括近1000个物种。我将使用这个数据库来测试有关生命周期进化的假设，例如复杂的生命周期寄生虫是否会变大或感染更多种类的宿主。这些分析将确定简单周期寄生虫和复杂周期寄生虫之间的关键区别。然后，我提议探索这种差异是如何在寄生虫基因组中表现出来的。我将使用现有的数据集，在独立的谱系中寻找共享的基因组特征，比如基因家族的扩张或选择性剪接的增加，这些特征将表明复杂生命周期带来的问题的一般解决方案。我还描述了转录学实验，评估不同宿主中的寄生虫阶段何时以及在多大程度上在基因上“脱钩”，即影响一个宿主中某一阶段的基因变化是否对其他宿主中的阶段产生了相关影响。通过结合表型、基因组和转录组方法，我希望揭示为什么(成本和收益)和如何(适应的遗传机制)复杂的生命周期进化。

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.