Biology subjects

Weissman, D. B.

Publications and source records attributed to Weissman, D. B..

15 recordsLinked to original sources

bioRxiv2026

Selection favors context-dependent bias in altruism

Altruism, in which individuals sacrifice some of their own reproduction to help others, can evolve if it is preferentially directed toward relatives. Organisms may recognize relatives through phenotypic similarity. Under the models originally studied by Hamilton, the threshold relatedness at which altruism becomes beneficial depends on the overall relatedness of the population. Implicit in this result is that natural selection may favor context-dependent strategies, in which donors judge their similarity to potential recipients relative to their similarity to the overall population when deciding whether to help. In this manuscript, we use a combination of simulations and theory to determine the circumstances under which context dependence is favored over simple strategies that do not depend on the observation of other interacting individuals. We find that a "plastic" strategy that uses the population context in its rule for donating consistently beats strategies that use only information about the potential recipient.

evolutionary biology↗

bioRxiv2025

Bursts of reproduction can create genetic structure in frequently recombining bacterial populations

In many bacterial species, strong genetic structure is present, where individuals are clustered into genetically distinct groupings within the species. However, high rates of homologous recombination have also been observed in many of these species, high enough that simple models of evolution predict that such genetic structure should be eliminated. One proposed resolution to this contradiction is the presence of recurrent bursts of reproduction caused by rapid adaptation or microepidemics. We investigate this hypothesis using coalescent simulations with recombination, focusing on the distribution of pairwise genetic distances. We show that bursty reproduction can indeed create genetic structure even when recombination is so frequent that all structure would be eliminated in the absence of bursts. We find that genetic structure is only possible when there is a burst of reproduction that is sufficiently large and recent in the populations history. In addition, we find that for other statistics beyond the distribution of pairwise distances, the simplest model of bursty reproduction does not produce distributions similar to those observed in nature. Interestingly, genetic structure from bursts of reproduction can appear among pairs of samples which do not share any genetic material by clonal descent, a feature which cannot be observed in populations whose structure is just a consequence of limited recombination.

evolutionary biology↗

bioRxiv2025

Transition of Staphylococcus aureus tetracycline resistance plasmid pT181 from independent multicopy replicon to predominantly integrated chromosomal element over 65 years

Mobile genetic elements (MGEs), including plasmids, phages and genome islands, are major sources of bacterial genetic diversity. The small plasmid pT181 confers tetracycline resistance in bacterial pathogen Staphylococcus aureus via an efflux pump, TetK. pT181 was one of the earliest sequenced S. aureus plasmids and has been isolated in both clinical and livestock-associated strains for decades, both as an independent replicon and integrated in the chromosome as part of staphylococcal cassette chromosome mec (SCCmec). Bacterial genome analysis tools and high-quality sequences with metadata are publicly available, but these resources remain underleveraged for examining historical data, especially when studying the spread of MGEs across a species and over time. Using publicly available reads and metadata, we explored the evolution of pT181 over nearly seven decades of samples to identify temporal trends in sequence evolution, copy number changes, and spread across S. aureus and beyond. pT181 was prevalent across S. aureus (found in 9.5% of 83,366 genomes tested), with a conserved sequence outside of three hypervariable regions. The history of pT181 since 1954 was characterized by spread across strains, significant variation in plasmid copy number of the independent replicon, and increasing frequency of integration of the plasmid into the S. aureus chromosome. We identified multiple chromosomal integration locations of the plasmid, including outside of the previously characterized SCCmec. We found that pT181 was transferred across Staphylococcaceae and into a Gram negative species. The repeated integration of pT181 into the chromosome may indicate coevolution of the plasmid and the host, potentially to facilitate increased antibiotic resistance.

genomics↗

bioRxiv2025

Genetic drift acts strongly on within-host influenza virus populations during acute infection but does not act alone

The evolutionary dynamics of seasonal influenza A viruses (IAVs) have been well characterized at the population level, with antigenic drift known to be a major force in driving strain turnover. The evolution of IAV populations at the within-host level, however, is still less well characterized. Improving our understanding of within-host IAV evolution has the potential to shed light on the source of new strains, including new antigenic variants, at the population level. Existing studies have pointed towards the role that stochastic processes play in shaping within-host viral evolution in acute infections of both humans and pigs. Here, we apply a population genetic model called the Beta-with-Spikes approximation to longitudinal intrahost Single Nucleotide Variant (iSNV) frequency data to quantify the extent of genetic drift acting on IAV populations at the within-host scale. We estimate small effective population sizes in both human IAV infections (NE = 41, 95% confidence interval: [22-72]) and swine IAV infections (NE = 10, 95% confidence interval: [8-14]). Moreover, we evaluate the consistency of the observed iSNV dynamics with Wright-Fisher model simulations. For the human IAV dataset that we analyze, we find that observed within-host IAV evolutionary dynamics are consistent with this classic model at the estimated low effective population size. However, for the swine IAV dataset, we find statistical evidence for rejecting the classic Wright-Fisher model as the only process governing within-host iSNV frequency dynamics. Our results contribute to the growing number of studies that point towards the important role of genetic drift in shaping patterns of genetic diversity in IAV populations within acutely infected hosts. It further raises questions about whether and what other processes, such as spatial compartmentalization, viral progeny production dynamics with strong skew, or selection, may be needed to explain patterns of within-host IAV evolution.

evolutionary biology↗

bioRxiv2025

The distribution of the time to the most recent pairwise genetic common ancestor of a set of sampled genomes

In a sample of chromosomes from a recombining population, each pair of individuals will have different most recent common genetic ancestors at different loci. We consider the distribution of the time to the most recent of these most recent common ancestors--the most recent time at which any pair of individuals in the sample share a common genetic ancestor at any locus. We use simple heuristic arguments, formal calculations, and coalescent simulations to find that as long as the chromosomal map length R is sufficiently long and the sample size n is not too large, the distribution of this time is peaked around a characteristic value. This value has the unusual scaling [Formula], where N is the effective size of the population.

evolutionary biology↗

bioRxiv2024

Effects of recombination on multi-drug resistance evolution in Plasmodium falciparum malaria

When multiple beneficial alleles are present in a population but not linked together in any one individual, there is no general evolutionary result that determines whether recombination will speed up or slow down the emergence and evolution of genotypes carrying multiple beneficial alleles. Translated to infectious disease control, this evolutionary uncertainty means that when multiple types of drug resistance are present we do not know whether recombination will act more strongly to (1) bring together single-resistant genotypes into multi-drug resistant (MDR) genotypes, or (2) break apart MDR genotypes into single-resistant genotypes. In this paper, we introduce a new version of an established and validated individual-based malaria transmission model where we have added individual mosquito bites, interrupted feeding by mosquitoes, 25 drug-resistance related loci, and individual recombination events of different Plasmodium falciparum genotypes inside the mosquito. Recombination among P. falciparum genotypes in this model occurs from two sources of variation, multi-clonal infections and interrupted feeding by mosquitoes, and we show that 80% to 97% of MDR recombinant falciparum genotypes are projected to occur from single uninterrupted bites on hosts with multi-clonal infections (for malaria prevalence > 5%). Increases in the models interrupted feeding rate slowly increase the number of recombination events occurring from interrupted feeds. A comparison of drug-resistance management strategies with this new model shows that, over a 15-year timeframe, triple artemisinin-combination therapies (ACT) strategies show the largest reductions in treatment failures and the longest delays until artemisinin resistance reaches a critical 1% threshold. Multiple first-line therapies (MFT) are second best under these criteria, and ACT cycling approaches are third best. MFT strategies generate a greater diversity of recombinant genotypes but fewer recombination events generating MDR and slower emergence of these recombinant MDR genotypes.

evolutionary biology↗

bioRxiv2023

Population structure can reduce clonal interference when sexual reproduction and dispersal are synchronized

In populations with limited recombination, clonal interference among beneficial mutations limits the maximum rate of adaptation. Spatial structure slows the spread of beneficial alleles; in purely asexual populations, this increases the amount of clonal interference. Beyond this extreme case, however, it is unclear how spatial structure and recombination interact to determine the amount of clonal interference. This interaction is particularly interesting because dispersal and recombination are often at least partially synchronized in natural populations, both at the individual and population levels, as when plants switch from vegetative growth to sexual reproduction or stress responses increase both motility and recombination in microbes. We simulate island models of populations evolving on a smooth fitness landscape and find that synchronized dispersal and sexual reproduction allow them to adapt faster than well-mixed populations of equal size. This is because the spatial structure preserves genetic diversity, while the synchronization increases the chance that recombination events occur between diverged individuals from different demes, i.e., the pairings where negative linkage disequilibrium can most effectively be reduced.

evolutionary biology↗

bioRxiv2022

50 shades of greenbeard: Robust evolution of altruism based on similarity of complex phenotypes

We study the evolution of altruistic behavior under a model where individuals choose to cooperate by comparing a set of continuous phenotype tags. Individuals play a donation game and only donate to other individuals that are sufficiently similar to themselves in a multidimensional phenotype space. We find the generic maintenance of robust altruism when phenotypes are multidimensional. Selection for altruism is driven by the coevolution of individual strategy and phenotype; altruism levels shape the distribution of individuals in phenotype space. Low donation rates induce a phenotype distribution that renders the population vulnerable to the invasion of altruists, whereas high donation rates prime a population for cheater invasion, resulting in cyclic dynamics that maintain substantial levels of altruism. Altruism is therefore robust to invasion by cheaters in the long term in this model. Furthermore, the shape of the phenotype distribution in high phenotype dimension--which is potentially more biologically relevant than low phenotype dimension--allows altruists to better resist the invasion by cheaters, and as a result the amount of donation increases with increasing phenotype dimension. We also generalize previous results in the regime of weak selection to two competing strategies in continuous phenotype space, and show that success under weak selection is crucial to success under strong selection in our model. Our results support the viability of a simple similarity-based mechanism for altruism in a well-mixed population.

evolutionary biology↗

bioRxiv2022

Detecting patterns of accessory genome coevolution in bacterial species using data from thousands of bacterial genomes

Bacterial genomes exhibit widespread horizontal gene transfer, resulting in highly variable genome content that complicates the inference of genetic interactions. In this study, we develop a method for detecting coevolving genes from large datasets of bacterial genomes that we call a "coevolution score". The method is based on pairwise comparisons of closely related individuals, analogous to a pedigree study in eukaryotic populations. This approach avoids the need for an accurate phylogenetic tree and allows very large datasets to be analyzed for signatures of recent coevolution. We apply our method to all of the more than 3 million pairs of genes from the entire annotated Staphylococcus aureus accessory genome of 2,756 annotated genes using a database of over 40,000 whole genomes. We find many pairs of genes that that appear to be gained or lost in a coordinated manner, as well as pairs where the gain of one gene is associated with the loss of the other. These pairs form networks of dozens of rapidly coevolving genes, primarily consisting of genes involved in metal resistance, virulence, mechanisms of horizontal gene transfer, and antibiotic resistance, particularly the SCCmec complex. Our results reflect the fact that the evolution of many bacterial pathogens since the middle of the twentieth century has largely been driven by antibiotic resistance gene gain, and in the case of S. aureus the SCCmec complex is the most prominent of these elements driving the evolution of resistance. The frequent coincidence of these gene gain or loss events suggests that S. aureus switch between antibiotic-resistant niches and antibiotic-susceptible ones. While we focus on gene gain and loss, our method can also detect genes which tend to acquire substitutions in tandem or, in datasets that include phenotypic information, genotype-phenotype or phenotype-phenotype coevolution.

genomics↗

bioRxiv2021

Heterogeneity in viral infections increases the rate of deleterious mutation accumulation

1RNA viruses have high mutation rates, with the majority of mutations being deleterious. We examine patterns of deleterious mutation accumulation over multiple rounds of viral replication, with a focus on how cellular coinfection and heterogeneity in viral output affect these patterns. Specifically, using agentbased intercellular simulations we find, in agreement with previous studies, that coinfection of cells by viruses relaxes the strength of purifying selection, and thereby increases the rate of deleterious mutation accumulation. We further find that cellular heterogeneity in viral output exacerbates the rate of deleterious mutation accumulation, regardless of whether this heterogeneity in viral output is stochastic or is due to variation in cellular multiplicity of infection. These results highlight the need to consider the unique life histories of viruses and their population structure to better understand observed patterns of viral evolution.

evolutionary biology↗

bioRxiv2020

Fitness dependence preserves selection for recombination across diverse mixed mating systems

Meiotic recombination and the factors affecting its rate and fate in nature have inspired many theoretical studies in evolutionary biology. Classical theoretical models have inferred that non-zero recombination can be favoured under a rather restricted parameter range. Thus, the ubiquity of recombination in nature remains an open question. However, these models assumed constant (uniform) recombination with an equal rate across all individuals within the population. Models of fitness-dependent recombination, with the rate varying among genotypes according to their fitness have shown that such a strategy can often be favoured over the best constant recombination. Here we use simulations to show that across a range of mating systems with varying frequencies of selfing and clonality, fitness-dependent recombination is often favoured even when any non-zero constant recombination is disfavoured. This recombination-protecting effect of fitness dependence is strongest under intermediate rates of selfing or high rates of clonality.

evolutionary biology↗

bioRxiv2020

Isolation by Distance in Populations with Long-Range Dispersal

Limited dispersal of individuals between generations results in isolation by distance, in which individuals further apart in space tend to be less related. Classic models of isolation by distance assume that dispersal distances are drawn from a thin-tailed distribution and predict that the proportion of the genome that is identical by descent between a pair of individuals should decrease exponentially with the spatial separation between them. However, in many natural populations, individuals occasionally disperse over very long distances. In this work, we use mathematical analysis and coalescent simulations to study the effect of long-range (power-law) dispersal on patterns of isolation by distance. We find that it leads to power-law decay of identity-by-descent at large distances with the same exponent as dispersal. We also find that broad power-law dispersal produces another, shallow power-law decay of identity-by-descent at short distances. These results suggest that the distribution of long-range dispersal events could be estimated from sequencing large population samples taken from a wide range of spatial scales.

evolutionary biology↗

bioRxiv2018

Increased adaptability to rapid environmental change can more than make up for the two-fold cost of males

The famous \"two-fold cost of sex\" is really the cost of anisogamy - why should females mate with males who do not contribute resources to offspring, rather than isogamous partners who contribute equally? In typical anisogamous populations, a single very fit male can have an enormous number of offspring, far larger than is possible for any female or isogamous individual. If the sexual selection on males aligns with the natural selection on females, anisogamy thus allows much more rapid adaptation via super-successful males. We show via simulations that this effect can be sufficient to overcome the two-fold cost and maintain anisogamy against isogamy in populations adapting to environmental change. The key quantity is the variance in male fitness - if this exceeds what is possible in an isogamous population, anisogamous populations can win out in direct competition by adapting faster.

evolutionary biology↗

bioRxiv2016

Minimal-assumption inference from population-genomic data

Samples of multiple complete genome sequences contain vast amounts of information about the evolutionary history of populations, much of it in the associations among polymorphisms at different loci. Current methods that take advantage of this linkage information rely on models of recombination and coalescence, limiting the sample sizes and populations that they can analyze. We introduce a method, Minimal-Assumption Genomic Inference of Coalescence (MAGIC), that reconstructs key features of the evolutionary history, including the distribution of coalescence times, by integrating information across genomic length scales without using an explicit model of recombination, demography or selection. Using simulated data, we show that MAGICs performance is comparable to PSMC on single diploid samples generated with standard coalescent and recombination models. More importantly, MAGIC can also analyze arbitrarily large samples and is robust to changes in the coalescent and recombination processes. Using MAGIC, we show that the inferred coalescence time histories of samples of multiple human genomes exhibit inconsistencies with a description in terms of an effective population size based on single-genome data.

evolutionary biology↗

bioRxiv2016

Ancestry in adapting, spatially-extended populations

Selective sweeps reduce neutral genetic diversity. In sexual populations, this \"hitchhiking\" effect is thought to be limited to the local genomic region of the sweeping allele. While this is true in panmictic populations, we find that in spatially-extended populations the combined effects of many unlinked sweeps can affect patterns of ancestry (and therefore neutral genetic diversity) across the whole genome. Even low rates of sweeps can be enough to skew the spatial locations of ancestors such that neutral mutations that occur in an individual living outside a small region in the center of the range have virtually no chance of fixing in the population. The fact that nearly all ancestry rapidly traces back to a small spatial region also means that relatedness between individuals falls off very slowly as a function of the spatial distance between them.

evolutionary biology↗