Towards Understanding Fine-Scale Microbial Diversity

DNA测序革命的一个重大发现是细菌种类的巨大数量。值得注意的是，这种细菌的生物多样性远远低于物种水平，一直延伸到最细微的遗传差异。对于常见的人类肠道细菌，地球两端的人可能有非常密切相关的菌株，而同一家庭的人可能有非常不同的菌株，个体可能有多种菌株，这些菌株不断竞争和进化。原绿球藻是一种在热带海洋中主导光合作用的微小而数量巨大的细菌，它固定的碳比所有农田加起来还多。对于原绿球藻来说，一桶海水中包含了许多菌株，有些是近亲，有些是远亲。对物种多样性的传统解释是，每个物种都有自己的生态位，或者生活在不同的地方，因此它们不会竞争。但对于相对简单的细菌来说，由于人类的运动和相互作用或洋流而混合在一起，每种菌株都有自己的生态位是不太可能的。为什么适者生存并没有导致几乎所有的物种灭绝？这个项目的目标就是开始解开这个谜团。这个项目将采用一系列的方法。一个主要部分将是开发和探索在微生物物种中创造和维持广泛多样性的潜在方案。为了理解情景是否以及如何起作用，我们将从理论上研究描绘最重要特征的简单模型。模型的简单性至关重要。另一种方法是制作尽可能逼真的模型，并在计算机上模拟它们，这是非常有问题的：人们如何才能了解哪些特征和预测可能适用于其他物种？但简单的模型并不意味着容易理解：该项目将涉及开发新的理论方法，结合生态学、进化论和统计物理学的方法。其中一个将被探索的场景来自细菌和噬菌体之间的永恒战斗——攻击细菌的病毒。如果一种噬菌体菌株有效地攻击一种丰富的细菌菌株，它可以杀死该菌株的大部分，为其他菌株留下繁殖空间，然后刺激其他噬菌体菌株进化以攻击它们，同时使能够抵抗最丰富的噬菌体的突变细菌产生和繁殖。这种“红皇后”式的动态——每个人都在努力保持原地不动——可能导致生态和进化的混乱状态，而这种状态可能会推动和维持广泛的多样性。该项目的一个关键部分是，从探索的每个场景中收集可能在《自然》中获得的预测，并找到测试这些预测的方法，特别是通过广泛的DNA测序。在理论发展的同时，该项目将涉及与微生物生态学家和实验人员合作，通过从自然环境或人类中提取的大量单细胞和大量类似细菌（和噬菌体）的DNA测序，深入探索几种细菌物种。要将多种类型的数据结合起来，并从中获得最重要的理解，就需要找到新的统计数量和测量方法，并对可能产生这些数据的过程进行数学分析。其中一个重要的问题是，细菌的进化在多大程度上是由它们之间的DNA交换决定的，甚至是由它们之间的DNA交换决定的。细菌长期以来被认为主要是无性的。了解生活在人身上或人体内或在环境中发挥关键作用的细菌物种的多样性和进化，对于人类健康和了解气候变化将如何影响塑造海洋和大气的基本过程非常重要。从科学的角度来看，物种内部的多样性是更高层次多样性发展的基础：加深对物种内部多样性的理解将更广泛地促进对进化和生物多样性的理解。该项目将汇集来自不同背景的学生和博士后，包括学术、物理、生物、计算机科学或统计学。对他们进行所有所需学科方面的培训对于项目的成功以及科学和科学家的更广泛发展都是重要的。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

A major discovery of the DNA sequencing revolution is the huge number of bacterial species. Remarkably, this bacterial biodiversity extends far below species level down to the finest scales of genetic differences. For common human gut bacteria, people on opposite sides of the Earth may have very closely related strains, while people in the same household may have very different strains, and individuals can have multiple strains that are continually competing and evolving. For Prochlorococcus, a tiny, enormously abundant bacterium that dominates photosynthesis in the tropical oceans and fixes more carbon than all croplands combined, a bucketful of seawater includes a multitude of strains, some closely related, some very distant. The traditional explanation for the diversity of species is that each has its own ecological niche, or live in different locations so they do not compete. But for relatively simple bacteria that are mixed together by human motion and their interactions or by ocean currents, it is implausible that each strain has its own ecological niche. Why doesn't survival of the fittest drive almost all the strains extinct? The goal of the Project is to begin to unravel this puzzle. This Project will bring a spectrum of approaches to bear. A major part will be developing and exploring potential scenarios for creating and sustaining extensive diversity within microbial species. To understand whether and how scenarios might work, simple models that caricature the most important features will be studied theoretically. The simplicity of models is essential. The alternate approach of making as-realistic-as-possible models and simulating them on computers is highly problematic: how could one learn which features and predictions might apply to other species? But simple models do not mean they are simple to understand: the Project will involve developing new theoretical methods combining approaches from ecology, evolution, and statistical physics. One of the scenarios that will be explored arises from the perpetual battle between bacteria and phages -- viruses that attack bacteria. If a phage strain effectively attacks an abundant bacterial strain, it can kill off much of that strain, leaving room for other strains to bloom, which then stimulate other phage strains to evolve to attack them, as well as enabling mutant bacteria that resist the most abundant phages to arise and prosper. This "Red Queen" dynamics -- everyone running hard just to stay in place -- can cause an ecological and evolutionary chaotic state that could potentially drive and sustain extensive diversity. A key part of this Project is, from each scenario explored, to glean predictions that might obtain in Nature and find ways of testing these, especially by extensive DNA sequencing. In parallel with the theoretical developments, the Project will involve collaborations with microbial ecologists and experimenters to explore several bacterial species in depth via DNA sequencing from large numbers of single cells and from large populations of similar bacteria (and phages) extracted from natural environments or humans. To combine data of multiple types, and to extract the most significant understanding, will involve finding new statistical quantities and methods to measure them, together with mathematical analyses of the processes that might produce them. One of the important questions is to what extent the evolution of bacteria -- long thought to be primarily asexual -- is shaped or even dominated by exchange of DNA between them. Understanding the diversity and evolution within bacterial species that live on or in humans, or play crucial roles in the environment, is important for human health and for understanding how climate change will affect the fundamental processes that shape the oceans and atmosphere. And scientifically, diversity within a species is the root from which higher level diversity develops: advancing understanding of it will advance understanding of evolution and bio-diversity more broadly. This Project will bring together students and postdocs from a spectrum of backgrounds, including, academically, physics, biology, and computer science or statistics. Training them in all the needed disciplines is important for the Project's success and for the broader development of science and scientists.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.