Hybridization breaks species barriers in long-term coevolution of a cyanobacterial population.

Bacterial species often undergo rampant recombination yet maintain cohesive genomic identity. Ecological differences can generate recombination barriers between species and sustain genomic clusters in the short term. But can these forces prevent genomic mixing during long-term coevolution? Cyanobacteria in Yellowstone hot springs comprise several diverse species that have coevolved for hundreds of thousands of years, providing a rare natural experiment.

Spatiotemporal ecological chaos enables gradual evolutionary diversification without niches or tradeoffs.

Ecological and evolutionary dynamics are intrinsically entwined. On short timescales, ecological interactions determine the fate and impact of new mutants, while on longer timescales evolution shapes the entire community. Here, we study the evolution of large numbers of closely related strains with generalized Lotka Volterra interactions but no niche structure.

Population genetics of polymorphism and divergence in rapidly evolving populations.

In rapidly evolving populations, numerous beneficial and deleterious mutations can arise and segregate within a population at the same time. In this regime, evolutionary dynamics cannot be analyzed using traditional population genetic approaches that assume that sites evolve independently. Instead, the dynamics of many loci must be analyzed simultaneously.

Synonymous mutations reveal genome-wide levels of positive selection in healthy tissues.

Genetic alterations under positive selection in healthy tissues have implications for cancer risk. However, total levels of positive selection across the genome remain unknown. Passenger mutations are influenced by all driver mutations, regardless of type or location in the genome.

Fundamental limits on the rate of bacterial growth and their influence on proteomic composition.

Despite abundant measurements of bacterial growth rate, cell size, and protein content, we lack a rigorous understanding of what sets the scale of these quantities and when protein abundances should (or should not) depend on growth rate. Here, we estimate the basic requirements and physical constraints on steady-state growth by considering key processes in cellular physiology across a collection of Escherichia coli proteomic data covering ≈4,000 proteins and 36 growth rates. Our analysis suggests that cells are predominantly tuned for the task of cell doubling across a continuum of growth rates; specific processes do not limit growth rate or dictate cell size.

Stabilization of extensive fine-scale diversity by ecologically driven spatiotemporal chaos.

It has recently become apparent that the diversity of microbial life extends far below the species level to the finest scales of genetic differences. Remarkably, extensive fine-scale diversity can coexist spatially. How is this diversity stable on long timescales, despite selective or ecological differences and other evolutionary processes? Most work has focused on stable coexistence or assumed ecological neutrality.

A model for the interplay between plastic tradeoffs and evolution in changing environments.

Performance tradeoffs are ubiquitous in both ecological and evolutionary modeling, yet they are usually postulated and built into fitness and ecological landscapes. However, tradeoffs depend on genetic background and evolutionary history and can themselves evolve. We present a simple model capable of capturing the key feedback loop: evolutionary history shapes tradeoff strength, which, in turn, shapes evolutionary future.

The evolutionary dynamics and fitness landscape of clonal hematopoiesis.

Somatic mutations acquired in healthy tissues as we age are major determinants of cancer risk. Whether variants confer a fitness advantage or rise to detectable frequencies by chance remains largely unknown. Blood sequencing data from ~50,000 individuals reveal how mutation, genetic drift, and fitness shape the genetic diversity of healthy blood (clonal hematopoiesis).

Adaptive walks on high-dimensional fitness landscapes and seascapes with distance-dependent statistics.

The dynamics of evolution is intimately shaped by epistasis - interactions between genetic elements which cause the fitness-effect of combinations of mutations to be non-additive. Analyzing evolutionary dynamics that involves large numbers of epistatic mutations is intrinsically difficult. A crucial feature is that the fitness landscape in the vicinity of the current genome depends on the evolutionary history.

The dynamics of adaptive genetic diversity during the early stages of clonal evolution.

The dynamics of genetic diversity in large clonally evolving cell populations are poorly understood, despite having implications for the treatment of cancer and microbial infections. Here, we combine barcode lineage tracking, sequencing of adaptive clones and mathematical modelling of mutational dynamics to understand adaptive diversity changes during experimental evolution of Saccharomyces cerevisiae under nitrogen and carbon limitation. We find that, despite differences in beneficial mutational mechanisms and fitness effects, early adaptive genetic diversity increases predictably, driven by the expansion of many single-mutant lineages.

Probing the ecological and evolutionary history of a thermophilic cyanobacterial population via statistical properties of its microdiversity.

Despite extensive DNA sequencing data derived from natural microbial communities, it remains a major challenge to identify the key evolutionary and ecological forces that shape microbial populations. We have focused on the extensive microdiversity of the cyanobacterium Synechococcus sp., which is a dominant member of the dense phototrophic biofilms in the hot springs of Yellowstone National Park.

Hidden Complexity of Yeast Adaptation under Simple Evolutionary Conditions.

Few studies have "quantitatively" probed how adaptive mutations result in increased fitness. Even in simple microbial evolution experiments, with full knowledge of the underlying mutations and specific growth conditions, it is challenging to determine where within a growth-saturation cycle those fitness gains occur. A common implicit assumption is that most benefits derive from an increased exponential growth rate.

Rapid adaptation in large populations with very rare sex: Scalings and spontaneous oscillations.

Genetic exchange in microbes and other facultative sexuals can be rare enough that evolution is almost entirely asexual and populations almost clonal. But the benefits of genetic exchange depend crucially on the diversity of genotypes in a population. How very rare recombination together with the accumulation of new mutations shapes the diversity of large populations and gives rise to faster adaptation is still poorly understood.

Development of a Comprehensive Genotype-to-Fitness Map of Adaptation-Driving Mutations in Yeast.

Adaptive evolution plays a large role in generating the phenotypic diversity observed in nature, yet current methods are impractical for characterizing the molecular basis and fitness effects of large numbers of individual adaptive mutations. Here, we used a DNA barcoding approach to generate the genotype-to-fitness map for adaptation-driving mutations from a Saccharomyces cerevisiae population experimentally evolved by serial transfer under limiting glucose. We isolated and measured the fitness of thousands of independent adaptive clones and sequenced the genomes of hundreds of clones.

Microbial diversity. Fine-scale diversity and extensive recombination in a quasisexual bacterial population occupying a broad niche.

Extensive fine-scale genetic diversity is found in many microbial species across varied environments, but for most, the evolutionary scenarios that generate the observed variation remain unclear. Deep sequencing of a thermophilic cyanobacterial population and analysis of the statistics of synonymous single-nucleotide polymorphisms revealed a high rate of homologous recombination and departures from neutral drift consistent with the effects of genetic hitchhiking. A sequenced isolate genome resembled an unlinked random mixture of the allelic diversity at the sampled loci.

Quantitative evolutionary dynamics using high-resolution lineage tracking.

Evolution of large asexual cell populations underlies ∼30% of deaths worldwide, including those caused by bacteria, fungi, parasites, and cancer. However, the dynamics underlying these evolutionary processes remain poorly understood because they involve many competing beneficial lineages, most of which never rise above extremely low frequencies in the population. To observe these normally hidden evolutionary dynamics, we constructed a sequencing-based ultra high-resolution lineage tracking system in Saccharomyces cerevisiae that allowed us to monitor the relative frequencies of ∼500,000 lineages simultaneously.

Acceleration of evolutionary spread by long-range dispersal.

The spreading of evolutionary novelties across populations is the central element of adaptation. Unless populations are well mixed (like bacteria in a shaken test tube), the spreading dynamics depend not only on fitness differences but also on the dispersal behavior of the species. Spreading at a constant speed is generally predicted when dispersal is sufficiently short ranged, specifically when the dispersal kernel falls off exponentially or faster.

Rapid evolution of adaptive niche construction in experimental microbial populations.

Many species engage in adaptive niche construction: modification of the local environment that increases the modifying organism's competitive fitness. Adaptive niche construction provides an alternative pathway to higher fitness, shaping the environment rather than conforming to it. Yet, experimental evidence for the evolutionary emergence of adaptive niche construction is lacking, leaving its role in evolution uncertain.

Lineage structure of the human antibody repertoire in response to influenza vaccination.

The human antibody repertoire is one of the most important defenses against infectious disease, and the development of vaccines has enabled the conferral of targeted protection to specific pathogens. However, there are many challenges to measuring and analyzing the immunoglobulin sequence repertoire, including that each B cell's genome encodes a distinct antibody sequence, that the antibody repertoire changes over time, and the high similarity between antibody sequences. We have addressed these challenges by using high-throughput long read sequencing to perform immunogenomic characterization of expressed human antibody repertoires in the context of influenza vaccination.

Genetic diversity and the structure of genealogies in rapidly adapting populations.

Positive selection distorts the structure of genealogies and hence alters patterns of genetic variation within a population. Most analyses of these distortions focus on the signatures of hitchhiking due to hard or soft selective sweeps at a single genetic locus. However, in linked regions of rapidly adapting genomes, multiple beneficial mutations at different loci can segregate simultaneously within the population, an effect known as clonal interference.

Denoising PCR-amplified metagenome data.

Background: PCR amplification and high-throughput sequencing theoretically enable the characterization of the finest-scale diversity in natural microbial and viral populations, but each of these methods introduces random errors that are difficult to distinguish from genuine biological diversity. Several approaches have been proposed to denoise these data but lack either speed or accuracy.

Results: We introduce a new denoising algorithm that we call DADA (Divisive Amplicon Denoising Algorithm).

The balance between mutators and nonmutators in asexual populations.

Mutator alleles, which elevate an individual's mutation rate from 10 to 10,000-fold, have been found at high frequencies in many natural and experimental populations. Mutators are continually produced from nonmutators, often due to mutations in mismatch-repair genes. These mutators gradually accumulate deleterious mutations, limiting their spread.

Determinism and stochasticity during maturation of the zebrafish antibody repertoire.

It is thought that the adaptive immune system of immature organisms follows a more deterministic program of antibody creation than is found in adults. We used high-throughput sequencing to characterize the diversifying antibody repertoire in zebrafish over five developmental time points. We found that the immune system begins in a highly stereotyped state with preferential use of a small number of V (variable) D (diverse) J (joining) gene segment combinations, but that this stereotypy decreases dramatically as the zebrafish mature, with many of the top VDJ combinations observed in 2-wk-old zebrafish virtually disappearing by 1 mo.

The rate of fitness-valley crossing in sexual populations.

Biological traits result in part from interactions between different genetic loci. This can lead to sign epistasis, in which a beneficial adaptation involves a combination of individually deleterious or neutral mutations; in this case, a population must cross a "fitness valley" to adapt. Recombination can assist this process by combining mutations from different individuals or retard it by breaking up the adaptive combination.