About

Benjamin Good is an assistant professor of applied physics at Stanford University. He is a theoretical biophysicist with a background in experimental evolution and population genetics. His research group focuses on the short-term evolutionary dynamics that emerge in rapidly evolving microbial populations, such as the gut microbiome. They utilize tools from statistical physics, population genetics, and computational biology to understand how microscopic growth processes and genome dynamics at the single-cell level give rise to collective behaviors observed at the population level. His projects range from basic theoretical investigations of non-equilibrium processes in microbial evolution and ecology to the development of new computational tools for measuring these processes in natural and experimental microbial communities. Through these efforts, he aims to uncover unifying theoretical principles that can help understand, forecast, and eventually control the ecological and evolutionary dynamics in diverse microbial scenarios.

Research topics

• Biology
• Ecology
• Genetics
• Evolutionary biology
• Computer Science
• Microbiology

Selected publications

• Genotype-fitness mapping of adaptive mutants reveals shifting low-dimensional structure across divergent environments

  PLoS Biology · 2026-03-26 · 1 citations

  articleOpen access

  A central goal in evolutionary biology is to predict the effect of a genetic mutation on fitness. This is a major challenge because it requires knowledge of both the phenotypic effects of a mutation and their importance in an arbitrary environment, which are high-dimensional quantities and difficult to guess a priori. Here, we address this problem by taking a top-down, data-driven approach to infer the mapping between genotypes, latent phenotypes, and fitness. We measure the fitness effects of a large collection of adaptive yeast mutants in many lab environments, from which we build low-dimensional, linear fitness landscapes. We find that these models are highly predictive of fitness variation for thousands of adaptive mutants, both in environments similar to where they evolved and also in divergent environments. This implies that the underlying genotype-phenotype-fitness maps for these adaptive mutants tend to be broadly low-dimensional. We further demonstrate that these maps only partially overlap across divergent environments, suggesting that the phenotypic determinants of fitness shift with the environment but remain low-dimensional. These results combine to emphasize the importance of environmental context in evolution, and suggest that top-down, low-dimensional fitness landscapes pave the way for evolutionary prediction.

  PublisherDOI

• Path-dependent recovery of the gut microbiome after antibiotics emerges from coupled ecological and evolutionary dynamics

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-23

  article

  Recovery of the gut microbiome after antibiotic exposure is often incomplete and variable, and the processes underlying this variation remain unclear. We performed longitudinal shotgun metagenomic sequencing of 2876 daily fecal samples from replicated humanized and conventional mouse cohorts exposed to controlled antibiotic perturbations. Metagenomic profiling recapitulated ecological trajectories previously observed by 16S sequencing, while revealing extensive strain-level dynamics, including reproducible sweeps of standing variants and de novo mutations in antibiotic target sites and regulatory loci. We also identified genetic changes whose effects depended on community composition, competitive release, and perturbation history. Cross-housing experiments revealed bidirectional strain transfer, with antibiotic-induced niche clearance enabling replacement of resident strains. In parallel, phage dynamics were heterogeneous and clustered by cage. Together, these findings show that post-antibiotic microbiome recovery is a path-dependent process shaped by selection, transmission, and phage activity, producing divergent outcomes even among closely matched communities exposed to the same perturbations.

  PublisherDOI

• Genome-scale resources in the infant gut symbiont Bifidobacterium breve reveal genetic determinants of colonization and host-microbe interactions

  Cell · 2025-03-10 · 19 citations

  article
  PublisherDOI

• Low-dimensional genotype-fitness mapping across divergent environments suggests a limiting functions model of fitness

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-09 · 4 citations

  preprintOpen access

  A central goal in evolutionary biology is to be able to predict the effect of a genetic mutation on fitness. This is a major challenge because fitness depends both on phenotypic changes due to the mutation, and how these phenotypes map onto fitness in a particular environment. Genotype, phenotype, and environment spaces are extremely large and complex, rendering bottom-up prediction difficult. Here we show, using a large collection of adaptive yeast mutants, that fitness across a set of lab environments can be well-captured by low-dimensional linear models of abstract genotype-phenotype-fitness maps. We find that these maps are low-dimensional not only in the environment where the adaptive mutants evolved, but also in divergent environments. We further find that the genotype-phenotype-fitness spaces implied by these maps overlap only partially across environments. We argue that these patterns are consistent with a "limiting functions" model of fitness, whereby only a small number of limiting functions can be modified to affect fitness in any given environment. The pleiotropic side-effects on non-limiting functions are effectively hidden from natural selection locally, but can be revealed globally. These results combine to emphasize the importance of environmental context in genotype-phenotype-fitness mapping, and have implications for the predictability and trajectory of evolution in complex environments.

  PublisherOA PDFDOI

• Competition for shared resources increases dependence on initial population size during coalescence of gut microbial communities

  Proceedings of the National Academy of Sciences · 2025-03-10 · 23 citations

  articleOpen access

  The long-term success of introduced populations depends on both their initial size and ability to compete against existing residents, but it remains unclear how these factors collectively shape colonization dynamics. Here, we investigate how initial population (propagule) size shapes the outcome of community coalescence by systematically mixing eight pairs of in vitro microbial communities at ratios that vary over six orders of magnitude, and we compare our results to neutral ecological theory. Although the composition of the resulting cocultures deviated substantially from neutral expectations, each coculture contained species whose relative abundance depended on propagule size even after ~40 generations of growth. Using a consumer-resource model, we show that this dose-dependent colonization can arise when resident and introduced species have high niche overlap and consume shared resources at similar rates. Strain isolates displayed longer-lasting dose dependence when introduced into diverse communities than in pairwise cocultures, consistent with our model's prediction that propagule size should have larger, more persistent effects in diverse communities. Our model also successfully predicted that species with similar resource-utilization profiles, as inferred from growth in spent media and untargeted metabolomics, would show stronger dose dependence in pairwise coculture. This work demonstrates that transient, dose-dependent colonization dynamics can emerge from resource competition and exert long-term effects on the outcomes of community coalescence.

  PublisherOA PDFDOI

• Dynamics of dN/dS within recombining bacterial populations

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-12

  preprintOpen accessSenior authorCorresponding

  The ratio of nonsynonymous to synonymous substitutions (dN/dS) encodes important information about the selection pressures acting on protein-coding genes. In bacterial populations, dN/dS often declines with the sequence divergence between strains, but the mechanisms responsible for this broad empirical trend are still debated. Existing models have primarily focused on de novo mutations, overlooking the older genetic variants that are continually introduced through horizontal gene transfer and recombination. Here we introduce a phenomenological model of dN/dS in recombining populations of bacteria, which allows us to disentangle the effects of recombination among pairs of closely related strains. We find that clonally inherited regions of the genome exhibit consistently higher dN/dS ratios, and that the accumulation of recombined segments can quantitatively explain the majority of the decline in dN/dS. We use these observations to re-examine models of purifying selection and adaptive reversion in human gut bacteria, and uncover evidence for widespread weak selection at a large fraction of protein coding sites. Our findings show that horizontal gene transfer can be an important factor in shaping genome-wide patterns of selective constraint, and raise new questions about the effectiveness of natural selection in complex bacterial populations.

  PublisherOA PDFDOI

• Community coalescence reveals strong selection and coexistence within species in complex microbial communities

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-07 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Complex microbial ecosystems harbor extensive intra-species diversity, but the fitness consequences of this genetic variation are poorly understood in community settings. Here we address this question by competing in vitro gut communities derived from different human donors, revealing the emergent fitness differences between conspecific strains as they competed within larger communities. Most pairs of strains experienced strong and context-dependent selection, even when their parent communities were originally selected in the same nutrient environment. However, these fitness differences typically attenuated over time due to biotic interactions within the community, leading to extended coexistence within many species, and competitive exclusion in others. These results support the view that conspecific strains can fulfill distinct ecological roles when competing within a diverse community, even when their genomic diversity exhibits the hallmarks of a single biological species.

  PublisherOA PDFDOI

• Modeling the Synergetic Dynamics of B cells and TFH cells in Germinal Center Reactions

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-01

  preprintOpen access

  Abstract B cells producing high-affinity antibodies arise through affinity maturation within germinal centers (GCs), where selection is driven by T follicular helper (T FH ) cells. Recent studies have shown that, like GC B cells, T FH cells also undergo antigen-dependent selection, with competition among T FH clones dictated by their ability to recognize and stimulate B cells. This sensitivity-dependent selection process leads to dynamic remodeling of the T FH repertoire over time. Despite the essential role of T FH cells in B cell selection, the functional consequences of the time evolution of the T FH cell population remains poorly understood. To address this gap, we developed a population dynamics model that explicitly incorporates key T FH cell properties and dynamics. Our analysis predicts that dynamic feedback between B and T FH cell populations provides robust homeostatic regulation of their numbers in the GC, yielding a stable lymphocyte ratio that we verify experimentally. Moreover, our model predicts that T FH clone sensitivity dictates distinct evolutionary strategies during affinity maturation, with low-sensitivity T FH cells accelerating affinity gain at the expense of B cell diversity, while high-sensitivity T FH cells slow affinity maturation but preserve a broader B cell repertoire. These findings highlight the importance of co-regulation between T FH and B cells and suggest that reciprocal stimulation allows the immune system to tune the tradeoff between the speed of affinity gain and the breadth of B cell diversity—a principle that may extend to other adaptive systems. Significance Statement Effector B cells that secrete high-affinity antibodies and form immunological memory are essential for humoral immunity and arise from germinal center (GC) reactions. Within GCs, B cells undergo an accelerated version of Darwinian evolution to enhance antibody affinity. This process is orchestrated by T follicular helper (T FH ) cells which provide stimulatory signals to selected B cells and undergo their own antigen-driven selection. To investigate this co-evolutionary process, we developed a tractable population-level model of the GC reaction. Our analysis reveals that the reciprocal stimulation of B and T FH cells provides a robust mechanism for regulating the B:T FH ratio and tuning the tradeoff between the speed of affinity maturation and the diversity of the antibody response.

  PublisherOA PDFDOI

• Abundance measurements reveal the balance between lysis and lysogeny in the human gut microbiome

  Current Biology · 2025-04-28 · 15 citations

  articleSenior author
  PublisherDOI

• Dynamics of local B cell migration during affinity maturation in the human tonsil

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-03

  preprintOpen accessCorresponding

  Affinity maturation enhances B cell binding within germinal centers, where spatial structure preserves sequence diversity by restricting cell movement. While recent studies show that some B cell lineages span multiple germinal centers, the sources, rates and consequences of this spreading process remain unknown. Here, we show that the spatial arrangement of B cells in the human tonsil is driven by local migration during affinity maturation. Through an evolutionary re-analysis of spatial transcriptomics data, we demonstrate that these local migrations follow a clock-like process, in which cells migrate at an average rate of ~1/50 cell divisions that is consistent across lineages and time. Migrating cells continue to evolve and diversify in their new germinal centers at similar rates, such that the largest lineages in each germinal center often originate from another. These results suggest that affinity maturation operates in a regime of pervasive but intermediate migration, balancing diversity and selection.

  PublisherDOI

Recent grants

• Quantitative approaches for mapping the real-time evolution of the gut microbiota

  NIH · $1.6M · 2022–2027

Frequent coauthors

• Michael M. Desai

  Quantitative BioSciences

  68 shared

• Kerwyn Casey Huang

  Stanford Medicine

  31 shared

• Katherine S. Pollard

  University of California, San Francisco

  23 shared

• Oskar Hallatschek

  University of California, Berkeley

  17 shared

• Ivana Cvijović

  Stanford University

  16 shared

• Justin L. Sonnenburg

  Chan Zuckerberg Initiative (United States)

  11 shared

• Stephen R. Quake

  Stanford University

  10 shared

• Dmitri A. Petrov

  Stanford University

  8 shared

Labs

• Benjamin Good LabPI

  Benjamin Good lab at Stanford University

Education

• Ph.D., Applied Physics

  Stanford University

  2005

• B.S., Physics

  University of California, Berkeley

  1999