Towards Understanding Fine-Scale Microbial Diversity

DNA测序革命的一个重大发现是大量的细菌物种。值得注意的是，这种细菌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相似的菌株，而同一家庭的人可能有非常不同的菌株，个人可能有多种不断竞争和进化的菌株。原氯球菌是一种微小的、极其丰富的细菌，它在热带海洋的光合作用中占据主导地位，固定的碳比所有农田的总和还要多。对于原氯球菌来说，一桶海水中含有大量菌株，其中一些关系密切，有些非常遥远。对物种多样性的传统解释是，每个物种都有自己的生态位，或者生活在不同的位置，所以它们不会竞争。但对于通过人类活动及其相互作用或洋流混合在一起的相对简单的细菌来说，每个菌株都有自己的生态位是不可能的。为什么适者生存不会导致几乎所有的品系灭绝？该项目的目标是开始解开这个谜团。这个项目将带来一系列可行的方法。一个主要部分将是开发和探索创造和维持微生物物种内广泛多样性的潜在方案。为了了解情景是否以及如何发挥作用，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真实的模型并在计算机上模拟它们，这是一个非常有问题的方法：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它们很容易理解：该项目将涉及开发新的理论方法，将生态学、进化论和统计物理学的方法结合起来。将探索的场景之一来自细菌和噬菌体之间的无休止的战斗--攻击细菌的病毒。如果一种噬菌体菌株有效地攻击了一种丰富的细菌菌株，它可以杀死该菌株的大部分，为其他菌株的繁殖留下空间，从而刺激其他噬菌体菌株进化攻击它们，并使抵抗最丰富的噬菌体的突变细菌能够出现并繁荣。这种“红皇后”的动态--每个人都在努力奔跑，只是为了留在原地--可能会导致生态和进化的混乱状态，这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，从探索的每一种情景中，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者的合作，通过从大量单细胞和从自然环境或人类中提取的大量类似细菌(和噬菌体)的DNA测序来深入探索几个细菌物种。要组合多种类型的数据，并提取最有意义的理解，将涉及找到新的统计量和方法来衡量它们，以及对可能产生这些统计量的过程进行数学分析。一个重要的问题是，细菌的进化--长期以来被认为主要是无性繁殖--在多大程度上受到它们之间DNA交换的影响，甚至是主导。了解生活在人类身上或在人类体内或在环境中扮演关键角色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至关重要。从科学上讲，物种内部的多样性是更高层次多样性发展的根源：推进对物种多样性的理解将促进对进化和更广泛的生物多样性的理解。这个项目将汇集来自不同背景的学生和博士后，包括学术上的物理、生物学、计算机科学或统计学。对他们进行所有所需学科的培训对项目的成功以及科学和科学家的更广泛发展都很重要。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.