Biology subjects

Abbara, A.

Publications and source records attributed to Abbara, A..

4 recordsLinked to original sources

bioRxiv2024

Impact of phylogeny on the inference of functional sectors from protein sequence data

Statistical analysis of multiple sequence alignments of homologous proteins has revealed groups of coevolving amino acids called sectors. These groups of amino-acid sites feature collective correlations in their amino-acid usage, and they are associated to functional properties. Modeling showed that nonlinear selection on an additive functional trait of a protein is generically expected to give rise to a functional sector. These modeling results motivated a principled method, called ICOD, which is designed to identify functional sectors, as well as mutational effects, from sequence data. However, a challenge for all methods aiming to identify sectors from multiple sequence alignments is that correlations in amino-acid usage can also arise from the mere fact that homologous sequences share common ancestry, i.e. from phylogeny. Here, we generate controlled synthetic data from a minimal model comprising both phylogeny and functional sectors. We use this data to dissect the impact of phylogeny on sector identification and on mutational effect inference by different methods. We find that ICOD is most robust to phylogeny, but that conservation is also quite robust. Next, we consider natural multiple sequence alignments of protein families for which deep mutational scan experimental data is available. We show that in this natural data, conservation and ICOD best identify sites with strong functional roles, in agreement with our results on synthetic data. Importantly, these two methods have different premises, since they respectively focus on conservation and on correlations. Thus, their joint use can reveal complementary information. Author SummaryProteins perform crucial functions in the cell. The biological function of a protein is encoded in its amino-acid sequence. Natural selection acts at the level of function, while mutations arise randomly on sequences. In alignments of sequences of homologous proteins, which share common ancestry and common function, the amino acid usages at different sites can be correlated due to functional constraints. In particular, groups of collectively correlated amino acids, termed sectors, tend to emerge due to selection on functional traits. However, correlations can also arise from the shared evolutionary history of homologous proteins, even without functional constraints. This may obscure the inference of functional sectors. By analyzing controlled synthetic data as well as natural protein sequence data, we show that two very different methods allow to identify sectors and mutational effects in a way that is most robust to phylogeny. We suggest that considering both of these methods allows a better identification of functionally important sites from protein sequences. These results have potential impact on the design of new functional sequences.

bioinformatics↗

bioRxiv2024

Mutant fate in spatially structured populations on graphs: connecting models to experiments

In nature, most microbial populations have complex spatial structures that can affect their evolution. Evolutionary graph theory predicts that some spatial structures modelled by placing individuals on the nodes of a graph affect the probability that a mutant will fix. Evolution experiments are beginning to explicitly address the impact of graph structures on mutant fixation. However, the assumptions of evolutionary graph theory differ from the conditions of modern evolution experiments, making the comparison between theory and experiment challenging. Here, we aim to bridge this gap by using our new model of spatially structured populations. This model considers connected subpopulations that lie on the nodes of a graph, and allows asymmetric migrations. It can handle large populations, and explicitly models serial passage events with migrations, thus closely mimicking experimental conditions. We analyze recent experiments in light of this model. We suggest useful parameter regimes for future experiments, and we make quantitative predictions for these experiments. In particular, we propose experiments to directly test our recent prediction that the star graph with asymmetric migrations suppresses natural selection and can accelerate mutant fixation or extinction, compared to a well-mixed population. Author SummaryPredicting how mutations spread through a population and eventually take over is important for understanding evolution. Complex spatial structures are ubiquitous in natural microbial populations, and can impact the fate of mutants. Theoretical models have been developed to describe this effect. They predict that some spatial structures have mutant fixation probabilities that differ from those of well-mixed populations. Experiments are beginning to probe these effects in the laboratory. However, there is a disconnect between models and experiments, because they consider different conditions. In this work, we connect them through a new model that closely matches experimental conditions. We analyze recent experiments and propose new ones that should allow testing the effects of complex population spatial structures on mutant fate.

biophysics↗

bioRxiv2023

Evolution of cooperation in deme-structured populations on graphs

Understanding how cooperation can evolve in populations despite its cost to individual cooperators is an important challenge. Models of spatially structured populations with one individual per node of a graph have shown that cooperation, modeled via the prisoners dilemma, can be favored by natural selection. These results depend on microscopic update rules, which determine how birth, death and migration on the graph are coupled. Recently, we developed coarse-grained models of spatially structured populations on graphs, where each node comprises a well-mixed deme, and where migration is independent from division and death, thus bypassing the need for update rules. Here, we study the evolution of cooperation in these models in the rare migration regime, within the prisoners dilemma. We find that cooperation is not favored by natural selection in these coarsegrained models on graphs where overall deme fitness does not directly impact migration from a deme. This is due to a separation of scales, whereby cooperation occurs at a local level within demes, while spatial structure matters between demes.

biophysics↗

bioRxiv2023

Frequent asymmetric migrations suppress natural selection in spatially structured populations

Natural microbial populations often have complex spatial structures. This can impact their evolution, in particular the ability of mutants to take over. While mutant fixation probabilities are known to be unaffected by sufficiently symmetric structures, evolutionary graph theory has shown that some graphs can amplify or suppress natural selection, in a way that depends on microscopic update rules. We propose a model of spatially structured populations on graphs directly inspired by batch culture experiments, alternating within-deme growth on nodes and migration-dilution steps, and yielding successive bottlenecks. This setting bridges models from evolutionary graph theory with Wright-Fisher models. Using a branching process approach, we show that spatial structure with frequent migrations can only yield suppression of natural selection. More precisely, in this regime, circulation graphs, where the total incoming migration flow equals the total outgoing one in each deme, do not impact fixation probability, while all other graphs strictly suppress selection. Suppression becomes stronger as the asymmetry between incoming and outgoing migrations grows. Amplification of natural selection can nevertheless exist in a restricted regime of rare migrations and very small fitness advantages, where we recover the predictions of evolutionary graph theory for the star graph.

biophysics↗