Towards Understanding Fine-Scale Microbial Diversity

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.