Genome evolution and radical lifestyle changes in eukaryotic microbes

进化轨迹的变化导致生物生物学的深刻改变，通常是在基因组组织的水平上。一个关键的例子是获得细胞内寄生生活方式后的基因组减少，这一现象已在细菌内共生体中进行了研究。真核生物的基因组比细菌的基因组更大、更复杂，生活方式改变对其基因组的影响尚不清楚。我的研究项目的长期目标是提高我们对真核生物基因组进化的理解，重点是生活史（如共生、寄生）和基因组形式/功能之间的关系。为此，我将研究重点放在ALVEOLATA的成员上，这是一组由顶复合体、鞭毛原虫和纤毛原虫组成的真核微生物。这个谱系特别适合研究这些问题。一方面，顶复合体从自由生活的单细胞藻类进化为高度特化的专性细胞内寄生虫，其中一些是非常危险的人类病原体，如疟疾和弓形虫病的病原体。顶复合体的近亲是鞭毛藻，它们共同表现出一系列令人眼花缭乱的不寻常的基因组特征，这些特征似乎在这些生物的进化中发挥了重要作用。本研究基于我们之前的工作，通过以下具体主题推进我们的目标：1)我们正在探索甲藻模式物种Oxyrrhis marina的基因组结构，其基因组比人类大8倍。我们的分析侧重于描述和分析基因组元素，这些元素被假设参与了这些基因组的大小扩展和其他不寻常的特征。我们也将使用生物化学和分子生物学的方法来解开他们的染色体的独特组织的秘密。我们的第二个重点是顶复合体。到目前为止，我们一直致力于阐明各种顶复合体谱系之间的关系，以便有一个坚实的系统发育框架来探索从自由生活的掠食性生物向高度特化的细胞内寄生虫过渡的细胞和基因组相关性。作为这一目标的一部分，我们将研究一种叫做肾霉菌的生物，它的生命周期独特地偏离了标准的顶端复合体的生活方式：肾霉菌不是在细胞内生长，而是侵入动物宿主的一个特殊器官，在那里它完成了它的生命周期，其中包括许多共存的细胞类型。与其他顶复合体形成鲜明对比的是，没有证据表明它对宿主致病，一些证据表明宿主与共生体之间存在代谢交换。我们期望这种独特的微生物将对寄生的起源及其后果提供实质性的启示。

Changes in evolutionary trajectories entail deep alterations in the biology of organisms, often at the level of genomic organization. A key example is genomic reduction after acquisition of an intracellular parasitic lifestyle, a phenomenon that has been investigated in bacterial endosymbionts. Eukaryotic genomes are larger and more complex than their bacterial counterparts, and the consequences of lifestyle changes on their genomes are poorly known. My research program has the long-term goal of improving our understanding of the evolution of eukaryotic genomes, with emphasis on the relationships between life history (e.g. symbiosis, parasitism) and genome form/function. To this aim, I focus my study on members of ALVEOLATA, a diverse group of eukaryotic microbes composed by apicomplexan, dinoflagellate and ciliate protozoa. This lineage is particularly well suited to investigate these questions. On one side, the apicomplexans evolved from free-living unicellular algae into highly specialized obligate intracellular parasites, some of which are very dangerous human pathogens such as the agents of malaria and toxoplasmosis. The closest relatives of apicomplexans are dinoflagellates, which collectively exhibit a bewildering array of unusual genomic features that appear to have played a major role in the evolution of these organisms. This proposal builds on our previous work advancing on our goals through the following specific topics: 1) we are exploring the genomic architecture of the dinoflagellate model species Oxyrrhis marina, whose genome is 8 times larger than human’s. Our analysis focuses on describing and analyzing genomic elements that are hypothetically involved in the size expansion and other unusual features of these genomes. We will also use biochemical and molecular biology approaches to unravel the secrets of the unique organization of their chromosomes. 2) Our second focus is on apicomplexans. So far we have been working on elucidating the relationships among the various apicomplexans lineages in order to have a solid phylogenetic framework to explore the cellular and genomic correlates of the transition from free-living and predatory organisms to highly specialized intracellular parasites. As part of this goal, we will investigate an organism called Nephromyces, whose life cycle uniquely deviates from the standard apicomplexan lifestyle: instead of growing intracellularly, Nephromyces invades a peculiar organ in their animal host where it completes its life cycle, which includes many coexisting cell types. In stark contrast to other apicomplexans, there is no evidence that it is pathogenic for its host, and some evidence points to metabolic exchanges between host and symbiont. We expect this unique microbe will shed substantial light on the origins of parasitism and its consequences.