Evolutionary dynamics of dense, spatially structured, and antagonistic microbial populations

摘要 宿主微生物组、人类感染和自然环境中的微生物通常在空间上生活在 结构化的聚集体，并且彼此对抗地相互作用。毒素介导拮抗 相互作用广泛存在于肠道，皮肤和其他人体微生物组中，并保护这些 反对外来入侵。最近的研究结果表明，空间结构可以强烈地 影响微生物种群的进化动力学，反过来，微生物之间的相互作用可以 空间结构的形成反馈。例如，我们发现机械相互作用 在不断生长的酵母菌落中， 在这些种群中，适应性较低的种群灭绝，适应性较强的种群扩张的速度。 尽管空间结构和微生物相互作用对进化有很大影响， 与人类健康相关的微生物动力学，我们所知道的关于微生物的大部分知识， 进化动力学来自于对混合良好的液体培养物进行的实验， 细胞之间的相互作用。为了填补这一空白，我的团队有兴趣定量地了解 空间结构、力学和生物相互作用如何影响适应性进化 微生物种群的动态。我们通过实验进化来解决这个问题， 合成生物学和数学建模。在初步实验中，我们发现， 选择在琼脂表面上快速扩增的酵母菌落导致细胞中的显著变化， 形状：细胞从椭圆形的祖先进化成细长的，几乎是杆状的。 比如，改变细胞在生长和分裂时的机械相互作用方式。我们假设 细长的细胞形状有利于更快的扩张，因为它减少了细胞 包装，这种适应性变化与基因型聚类方式的变化有关 在空间导致增加的遗传漂变，等位基因频率的时间变化，由于 偶然事件。最近，我们证明了一种产毒微生物只能侵入 如果其接种物大于临界大小，则由较弱的毒素生产者占据，并且适应性 进化可以改变对抗的动力。我们将通过实验研究 关键接种量对相互作用强度的依赖性，我们将研究如何 空间结构控制着突变的命运，这些突变赋予了对毒素的抗性， 无论是入侵者还是常驻菌株。最后，我们将研究如何拮抗相互作用 影响小杆线虫肠道入侵动力学的微生物 elegans：这些实验将帮助我们将在简单的实验室环境中获得的结果转化为 更复杂但更现实的宿主微生物组入侵动力学。

Abstract Microbes in host microbiomes, human infections and the natural environment often live in spatially structured aggregates and interact antagonistically with each other. Toxin-mediated antagonistic interactions are widespread in the gut, skin, and other human microbiomes, and protect these communities against external invasion. Recent results suggest that spatial structure can strongly affect the evolutionary dynamics of microbial populations, and, in turn, microbial interactions can feedback on the formation of spatial structure. For example, we found that mechanical interactions among dividing cells in growing yeast colonies reduce the power of natural selection by reducing the rates at which lower fitness strains go extinct and fitter ones expand in these populations. Despite spatial structure and microbial interactions have a strong impact on the evolutionary dynamics of microbes relevant for human health, most of what we know about microbial evolutionary dynamics comes from experiments with well-mixed liquid cultures with limited interactions among cells. To fill this gap, my group is interested in understanding quantitatively how spatial structure, mechanics and biological interactions impact the adaptive evolutionary dynamics of microbial populations. We approach this question via experimental evolution, synthetic biology, and mathematical modeling. In preliminary experiments, we found that evolving yeast colonies selecting for faster expansion on agar surfaces results in notable changes in cell shape: cells evolved from an ellipsoidally shaped ancestor to being elongated and almost rod- like, changing the way cells interact mechanically when growing and dividing. We hypothesize that an elongated cell shape is advantageous for faster expansion because it reduces cell packing, and that this adaptive change is associated with changes in the way genotypes cluster in space leading to increased genetic drift, the temporal change in allele frequencies due to chance events. Recently, we showed that a toxin-producing microbe can only invade a landscape occupied by a weaker toxin-producer if its inoculum is larger than a critical size, and that adaptive evolution can alter the dynamics of antagonism. We will experimentally investigate the dependence of the critical inoculum size on the strength of the interaction, and we will study how spatial structure controls the fate of mutations that confer resistance to the toxin produced by either the invader or resident strain. Finally, we will investigate how antagonistic interactions among microbes affect the dynamics of invasion in the gut of the nematode Caenorhabditis elegans: these experiments will help us translate results obtained in simple laboratory settings to the more complicated but more realistic dynamics of invasion of a host microbiome.