More Like this

1. Fixation probabilities in graph-structured populations under weak selection

   https://doi.org/10.1371/journal.pcbi.1008695  

   Allen, Benjamin; Sample, Christine; Steinhagen, Patricia; Shapiro, Julia; King, Matthew; Hedspeth, Timothy; Goncalves, Megan (February 2021, PLOS Computational Biology)

   Traulsen, Arne (Ed.)

   A population’s spatial structure affects the rate of genetic change and the outcome of natural selection. These effects can be modeled mathematically using the Birth-death process on graphs. Individuals occupy the vertices of a weighted graph, and reproduce into neighboring vertices based on fitness. A key quantity is the probability that a mutant type will sweep to fixation, as a function of the mutant’s fitness. Graphs that increase the fixation probability of beneficial mutations, and decrease that of deleterious mutations, are said to amplify selection. However, fixation probabilities are difficult to compute for an arbitrary graph. Here we derive an expression for the fixation probability, of a weakly-selected mutation, in terms of the time for two lineages to coalesce. This expression enables weak-selection fixation probabilities to be computed, for an arbitrary weighted graph, in polynomial time. Applying this method, we explore the range of possible effects of graph structure on natural selection, genetic drift, and the balance between the two. Using exhaustive analysis of small graphs and a genetic search algorithm, we identify families of graphs with striking effects on fixation probability, and we analyze these families mathematically. Our work reveals the nuanced effects of graph structure on natural selection and neutral drift. In particular, we show how these notions depend critically on the process by which mutations arise. 

   more » « less
2. Mutant fixation in the presence of a natural enemy

   https://doi.org/10.1038/s41467-023-41787-5  

   Wodarz, Dominik; Komarova, Natalia L. (October 2023, Nature Communications)

   Abstract The literature about mutant invasion and fixation typically assumes populations to exist in isolation from their ecosystem. Yet, populations are part of ecological communities, and enemy-victim (e.g. predator-prey or pathogen-host) interactions are particularly common. We use spatially explicit, computational pathogen-host models (with wild-type and mutant hosts) to re-visit the established theory about mutant fixation, where the pathogen equally attacks both wild-type and mutant individuals. Mutant fitness is assumed to be unrelated to infection. We find that pathogen presence substantially weakens selection, increasing the fixation probability of disadvantageous mutants and decreasing it for advantageous mutants. The magnitude of the effect rises with the infection rate. This occurs because infection induces spatial structures, where mutant and wild-type individuals are mostly spatially separated. Thus, instead of mutant and wild-type individuals competing with each other, it is mutant and wild-type “patches” that compete, resulting in smaller fitness differences and weakened selection. This implies that the deleterious mutant burden in natural populations might be higher than expected from traditional theory. 

   more » « less
3. Fixation dynamics on hypergraphs

   https://doi.org/10.1371/journal.pcbi.1011494  

   Liu, Ruodan; Masuda, Naoki (September 2023, PLOS Computational Biology)

   Wodarz, Dominik (Ed.)

   Hypergraphs have been a useful tool for analyzing population dynamics such as opinion formation and the public goods game occurring in overlapping groups of individuals. In the present study, we propose and analyze evolutionary dynamics on hypergraphs, in which each node takes one of the two types of different but constant fitness values. For the corresponding dynamics on conventional networks, under the birth-death process and uniform initial conditions, most networks are known to be amplifiers of natural selection; amplifiers by definition enhance the difference in the strength of the two competing types in terms of the probability that the mutant type fixates in the population. In contrast, we provide strong computational evidence that a majority of hypergraphs are suppressors of selection under the same conditions by combining theoretical and numerical analyses. We also show that this suppressing effect is not explained by one-mode projection, which is a standard method for expressing hypergraph data as a conventional network. Our results suggest that the modeling framework for structured populations in addition to the specific network structure is an important determinant of evolutionary dynamics, paving a way to studying fixation dynamics on higher-order networks including hypergraphs. 

   more » « less
4. Multiple infection of cells changes the dynamics of basic viral evolutionary processes

   https://doi.org/10.1002/evl3.95  

   Wodarz, Dominik; Levy, David_N; Komarova, Natalia_L (February 2019, Evolution Letters)

   Abstract The infection of cells by multiple copies of a given virus can impact viral evolution in a variety of ways, yet some of the most basic evolutionary dynamics remain underexplored. Using computational models, we investigate how infection multiplicity affects the fixation probability of mutants, the rate of mutant generation, and the timing of mutant invasion. An important insight from these models is that for neutral and disadvantageous phenotypes, rare mutants initially enjoy a fitness advantage in the presence of multiple infection of cells. This arises because multiple infection allows the rare mutant to enter more target cells and to spread faster, while it does not accelerate the spread of the resident wild-type virus. The rare mutant population can increase by entry into both uninfected and wild-type-infected cells, while the established wild-type population can initially only grow through entry into uninfected cells. Following this initial advantageous phase, the dynamics are governed by drift or negative selection, respectively, and a higher multiplicity reduces the chances that mutants fix in the population. Hence, while increased infection multiplicity promotes the presence of neutral and disadvantageous mutants in the short-term, it makes it less likely in the longer term. We show how these theoretical insights can be useful for the interpretation of experimental data on virus evolution at low and high multiplicities. The dynamics explored here provide a basis for the investigation of more complex viral evolutionary processes, including recombination, reassortment, as well as complementary/inhibitory interactions. 

   more » « less
5. Causal Inference Despite Limited Global Confounding via Mixture Models

   Gordon, S.; Mazaheri, B.; Rabani, Y.; Schulman, L. (April 2023, Proceedings of Machine Learning Research)

   van der Schaar, M.; Zhang, C.; Janzing, D. (Ed.)

   A Bayesian Network is a directed acyclic graph (DAG) on a set of n random variables (the vertices); a Bayesian Network Distribution (BND) is a probability distribution on the random variables that is Markovian on the graph. A finite k-mixture of such models is graphically represented by a larger graph which has an additional “hidden” (or “latent”) random variable U, ranging in {1,...,k}, and a directed edge from U to every other vertex. Models of this type are fundamental to causal inference, where U models an unobserved confounding effect of multiple populations, obscuring the causal relationships in the observable DAG. By solving the mixture problem and recovering the joint probability distribution with U, traditionally unidentifiable causal relationships become identifiable. Using a reduction to the more well-studied “product” case on empty graphs, we give the first algorithm to learn mixtures of non-empty DAGs. 

   more » « less