Biology subjects

Bollback, J. P.

Publications and source records attributed to Bollback, J. P..

5 recordsLinked to original sources

bioRxiv2025

CRISPR herd immunity against a transducing phage underlies adaptive homologous recombination in resting bacteria

Homologous recombination (HR) is ubiquitous across evolution, driving adaptation by reshuffling standing genetic variation. Although bacteria lack meiotic recombination, HR extensively shapes their genomes. However, the mechanisms and ecological conditions sustaining frequent HR in bacteria remain unclear. Using Escherichia coli, we reveal how frequent recombination emerges from herd immunity to a generalized transducing phage. Herd immunity-established here via CRISPR immunity-maintains genetic polymorphism and enables stable host-phage coexistence, thereby promoting genome-wide gene flow and accelerating adaptation through recombination up to two orders of magnitude relative to de novo mutations. Notably, we show that recombination occurs in stationary phase and is mediated by RecG, which has been previously reported to be regulated by the stringent response - a bacterial reaction to nutrient deprivation and other stress conditions. Bacterial herd immunity thus fulfills an unexpected role of promoting adaptation by HR. This mechanism helps explain the enigmatic high rates of HR across bacterial populations, clarifies how bacteria adapt as resources wane, and suggests a broader evolutionary role for bacterial immune systems beyond individual defense.

evolutionary biology↗

bioRxiv2022

Environment and the Evolutionary Trajectory of Horizontal Gene Transfer.

Horizontal gene transfer (HGT) is a powerful evolutionary force facilitating bacterial adaptation and emergence of novel phenotypes. Several factors, including environmental ones, are predicted to restrict HGT, but we lack systematic and experimental data supporting these predictions. Here, we address this gap by measuring the relative fitness of genes horizontally transferred from E. coli to S. enterica in infection relevant environments. We estimated the distribution of fitness effects in each environment and identified dosage-dependent effects across different environments are a significant barrier to HGT. The majority of genes were found to be deleterious. We also found longer genes had stronger negative fitness consequences than shorter ones, showing that gene length can significantly hinder HGT. Furthermore, fitness effects of transferred genes were found to be environmentally dependent. In summary, a substantial fraction of transferred genes had a significant fitness cost on the recipient, with both gene characteristics and the environment acting as evolutionary barriers to HGT.

microbiology↗

bioRxiv2020

Structure and Evolution of Constitutive Bacterial Promoters

Predicting gene expression levels from any DNA sequence is a major challenge in biology. Using libraries with >25,000 random mutants, we developed a biophysical model that accounts for major features of {sigma}70-binding bacterial promoters to accurately predict constitutive gene expression levels of any sequence. We experimentally and theoretically estimated that 10-20% of random sequences lead to expression and 82% of non-expressing sequences are one point mutation away from a functional promoter. Generating expression from random sequences is pervasive, such that selection acts against {sigma}70-RNA polymerase binding sites even within inter-genic, promoter-containing regions. The pervasiveness of {sigma}70- binding sites, which arises from the structural features of promoters captured by our biophysical model, implies that their emergence is unlikely the limiting step in gene regulatory evolution.

evolutionary biology↗

bioRxiv2019

Experimental Determination of Evolutionary Barriers to Horizontal Gene Transfer

Horizontal gene transfer, the acquisition of genes across species boundaries, is a major source of novel phenotypes. Several barriers have been suggested to impede the likelihood of horizontal transmission; however experimental evidence is scarce. We measured the fitness effects of genes transferred from Salmonella enterica serovar Typhimurium to Escherichia coli, and found that most result in strong fitness costs. Previously identified evolutionary barriers -- gene function and the number of protein-protein interactions -- did not predict the fitness effects of transferred genes. In contrast, dosage sensitivity, gene length, and the intrinsic protein disorder significantly impact the likelihood of a successful horizontal transfer. While computational approaches have been successful in describing long-term barriers to horizontal gene transfer, our experimental results identified previously underappreciated barriers that determine the fitness effects of newly transferred genes, and hence their short-term eco-evolutionary dynamics.

microbiology↗

bioRxiv2017

CRISPR-based Herd Immunity Limits Phage Epidemics in Bacterial Populations

Pathogens are a driving force in evolution, giving rise to a diversity of host immune defenses. In order for a pathogen to spread in a population a sufficient number of its members must be susceptible to infection, as resistant individuals can prevent the spread of a pathogen among susceptible hosts in a process known as herd immunity. While herd immunity has been extensively studied in vertebrate populations, little is known about its role, if any, in the dynamics between bacteria and their phage pathogens. Here we explore the dynamics of T7 phage epidemics in structured and unstructured Escherichia coli populations consisting of differing mixtures of susceptible and resistant individuals harboring CRISPR immunity to the phage. Using both experiments and mathematical modelling we describe the conditions under which herd immunity arises in bacterial populations. Notably, the effects of herd immunity depend strongly on the presence of spatial structure in the population, the bacterial growth rate, and phage replication rate. The results of our model can apply to other host-pathogen systems to determine the herd immunity threshold from the relative speed of an epidemic wave in partially resistant populations. In addition, our findings suggest that herd immunity plays an important role in bacterial communities, as seen in other host-pathogen systems, allowing for stable coexistence of bacteria and their phages and the maintenance of polymorphism in bacterial immunity.

evolutionary biology↗