Biology subjects

Hogeweg, P.

Publications and source records attributed to Hogeweg, P..

11 recordsLinked to original sources

bioRxiv2026

High-dimensional HIV-1 quasispecies modeling guides escape-proof antibody design

Rapidly evolving viruses form diverse quasispecies that enable escape from immune responses and treatments. For example, HIV-1 can rebound within weeks of broadly neutralizing antibody (bNAb) treatment through the outgrowth of high-fitness escape mutants in the quasispecies or the evolution of new escape variants. Most existing models of viral dynamics consider only a small number of viral variants and either assume arbitrary mutant fitness distributions or require extensive fitting to sparse clinical data. Here, we develop a high-dimensional HIV-1 quasispecies model that captures the dynamics of millions of viral strains and parameterize this using in silico binding affinity predictions. Without fitting to experimental data, the model qualitatively reproduces viral rebound following bNAb treatment. Lower-dimensional model projections recover these dynamics only when informed by features derived from the high-dimensional model. Finally, we use the model to develop a quasispecies-based framework for antibody optimization and identify antibodies predicted to effectively suppress viremia. Together, our results demonstrate that integrating mechanistic genotype-phenotype maps with high-dimensional quasispecies models provides unprecedented insights into viral evolution.

systems biology↗

bioRxiv2025

Natural protein structures have evolved exceptional robustness to mutations

Protein structures are often conserved across widely divergent sequences, suggesting high mutational robustness. However, how such robustness emerges through evolution, and how it relates to the underlying sequence-structure map, remains poorly understood. In contrast, the mutational profiles (distribution of structures upon point mutation) of RNA secondary structures are well characterised, exhibiting both high mutational robustness and high evolvability through mutational access to diverse folds. The recent revolution in protein structure prediction now enables analagous large-scale analyses for proteins. Here, we use the structure prediction algorithm ESMFold to systematically investigate the mutational profiles of natural, random, and de novo proteins. Unlike RNA, where functional and random sequences share similar mutational profiles, natural proteins are substantially more robust than random amino acid sequences, suggesting an evolutionary drive toward robustness. They also exhibit limited structural variation among close sequence neighbours, potentially constraining access to new folds. Interestingly, many de novo proteins do resemble random sequences in their mutational profiles, with low robustness relative to established proteins. These findings reveal how gene duplication and de novo gene birth follow distinct evolutionary trajectories toward functional proteins and highlight a potential role for large-effect mutations in the emergence of structural complexity.

evolutionary biology↗

bioRxiv2025

The risk of sexual reproduction promotes the evolution of regulation between host and symbionts

Sexual reproduction is a widely spread feature of eukaryotes and was already present in the last eukaryotic common ancestor (LECA). Most extant eukaryotes inherit mitochondria from a single parent, but the mechanisms enforcing uniparental inheritance vary widely. Yet, because the first eukaryotes would not have evolved such mechanisms, sexual cell fusion would have inherently led to mitochondrial mixing. Here, we explore the evolutionary consequences of biparental inheritance of endosymbionts during host-symbiont co-evolution using a multilevel, individual-based model of endosymbiosis. Our results show that biparental inheritance introduces evolutionary conflict, as it facilitates the spread of fast-replicating symbionts, which can drive host populations to extinction. However, in a diverse environment, holobionts diversify and adapt to distinct niches, protecting the population from total collapse caused by selfish symbionts. Moreover, this conflict can be resolved through the evolution of signaling mechanisms that allow hosts to regulate symbiont cell cycles. In many cases, sexually reproducing populations not only survive but also outperform their asexual counterparts. We conclude that sexual reproduction could have appeared early during eukaryogenesis.

evolutionary biology↗

bioRxiv2023

Eco-evolutionary dynamics of massive, parallel bacteriophage outbreaks in compost communities

Bacteriophages are important drivers of microbial ecosystems, yet their dynamics in complex natural communities remain poorly understood compared to simplified laboratory systems. To address this gap, we analyzed viral dynamics across 20 compost-derived microbial communities propagated for one year in mesocosms. Communities clustered into two distinct types, each dominated by different cellulose-degraders and comprising hundreds of genera. In one type, we observed massive, parallel outbreaks of Theomophage, a previously undescribed bacteriophage, reaching 74% of metagenomic sequencing reads, the largest bacteriophage outbreak documented to date. Theomophage populations in isolated communities were composed of a single genotype that showed striking evolutionary stability throughout the experiment. In contrast, following experimental viral migration between mesocosms, all Theomophage populations showed rapid evolution via recombination between preexisting genotypes, replacement of ancestral lineages, and, upon successful migration to mesocosms of the alternate community type where Theomophage was initially absent, rapid acquisition of novel mutations that swept local populations and then spread to other mesocosms. Our study reveals the spatial and temporal scales at which bacteriophage microdiversity evolves in complex communities. It further shows that mixing of viral communities -- likely common in natural systems -- can rapidly accelerate bacteriophage evolution.

microbiology↗

bioRxiv2023

Intracellular signaling in proto-eukaryotes evolves to alleviate regulatory conflicts of endosymbiosis

The complex eukaryotic cell resulted from a merger between simpler prokaryotic cells, yet the relative timing and the role of the mitochondrial endosymbiosis with respect to other eukaryotic innovations has remained under dispute. Although expansion of the regulatory repertoire has been inferred from phylogenetic studies, gene regulation has not been taken into account in current scenarios of the mitochondrial endosymbiosis which mostly focus on the complementary energetic and ecological perspectives. The endosymbiotic state introduced several unique challenges to cells such as coordination of host and symbiont cell cycles and its disruption by leaking gene products and DNA fragments between host and symbionts. To investigate how these unique challenges impacted genome and network evolution during eukaryogenesis, we study a constructive computational model where two simple cells are forced into an obligate endosymbiosis. Across multiple in silico evolutionary replicates, we observe the emergence of different mechanisms for the coordination of host and symbiont cell cycles, stabilizing the endosymbiotic relationship. The most commonly evolved mechanism, implicit control, works without signaling between host and symbiont. Signaling only evolves under the influence of leaking gene products, while such regulatory interference is inherently harmful. In the fittest evolutionary replicate, the host controls the symbiont cell cycle entirely through signaling, mimicking the regulatory dominance of the nucleus over the mitochondrion that evolved during eukaryogenesis.

evolutionary biology↗

bioRxiv2022

Obligate Endosymbiosis Explains Genome Expansion During Eukaryogenesis

The endosymbiosis of an alpha-proteobacterium that gave rise to mitochondria was one of the key events in eukaryogenesis. Common patterns in eukaryogenesis and present-day endosymbiotic relations include genomic streamlining of the symbiont, endosymbiotic gene transfer, and regulatory control by the host through protein targeting to the symbiont. One unique outcome for eukaryogenesis was a much more complex cell with a large genome, which may or may not be related to the mitochondrial endosymbiosis. Despite the existence of many plausible hypotheses for the observed patterns, a constructive evolutionary model in which these hypotheses can be studied is still lacking. Here we construct an evolutionary model of cell-cycle regulation to study how obligate endosymbiosis between two prokaryote-like cells impacts cellular behavior and genome evolution. The model does not predefine an explicit fitness criterion and thereby allows for the evolution of various emergent behaviors. For instance, even though we do not allow for communication between host and symbiont, they achieve implicit cell-cycle coordination through their interaction with the environment. This evolved cell-cycle coordination can drive genome expansion as well as symmetry breaking in genome size. Many replicate runs of our evolution experiment yield organisms with a large host and small symbiont genome, but interestingly, some yield the opposite. Still on long timescales, organisms with a large host and small symbiont genome perform best, and mimic the outcome of eukaryogenesis. By designing and studying a constructive evolutionary model of obligate endosymbiosis, we uncovered some of the forces that may drive the patterns observed in nature. Our results provide a theoretical foundation for patterns related to the mitochondrial endosymbiosis, such as genome size asymmetry, and reveal evolutionary outcomes that have not been considered so far, such as cell-cycle coordination without direct communication.

evolutionary biology↗

bioRxiv2022

On specialists and generalists: niche range strategies across the tree of life

Generalists can survive in many environments whereas specialists have a limited distribution. Although a classical concept in ecology, niche breadth has remained challenging to quantify because it depends on an objective definition of the environment. Here, by defining the environment of a microbe as the community it resides in, we integrated information from over 22 thousand environmental sequencing samples to derive a quantitative social niche breadth score for all microbial taxa. At the level of genera, we explored niche range strategies across the tree of life. We found that generalists include opportunists that stochastically dominate local communities, while specialists are stable but low in abundance. Generalists have a more diverse and open pan genome than specialists, but we found no global correlation between niche breadth and genome size. Instead, we observed two distinct evolutionary strategies, where specialists have relatively small genomes in habitats with low local diversity, but relatively large genomes in habitats with high local diversity. Together, our global analysis shines a new, data-driven light on microbial niche range strategies.

bioinformatics↗

bioRxiv2021

Evolution of Regulatory Complexity for Cell-Cycle Control

How complexity arises is a fundamental evolutionary question. Complex gene regulation is thought to arise by the interplay between adaptive and non-adaptive forces at multiple organizational levels. Using a computational model, we investigate how complexity arises in cell-cycle regulation. Starting from the well-known Caulobacter crescentus network, we study how cells adapt their cell-cycle behaviour to a gradient of limited nutrient conditions using 10 replicate in silico evolution experiments. We find adaptive expansion of the gene regulatory network: improvement of cell-cycle behaviour allows cells to overcome the inherent cost of complexity. Replicates traverse different evolutionary trajectories leading to distinct eco-evolutionary strategies. In four replicates, cells evolve a generalist strategy to cope with a variety of nutrient levels; in two replicates, different specialist cells evolve for specific nutrient levels; in the remaining four replicates, an intermediate strategy evolves. The generalist and specialist strategies are contingent on the regulatory mechanisms that arise early in evolution, but they are not directly linked to network expansion and overall fitness. This study shows that functionality of cells depends on the combination of gene regulatory network topology and genome structure. For example, the positions of dosage-sensitive genes are exploited to signal to the regulatory network when replication is completed, forming a de novo evolved cell-cycle checkpoint. Complex gene regulation can arise adaptively both from expansion of the regulatory network and from the genomic organization of the elements in this network, demonstrating that to understand complex gene regulation and its evolution, it is necessary to integrate systems that are often studied separately.

evolutionary biology↗

bioRxiv2021

Nothing in evolution makes sense except in the light of parasites

Parasitism emerges readily in models and laboratory experiments of RNA world and would lead to extinction unless prevented by compartmentalisation or spatial patterning. Modelling replication as an active computational process opens up many degrees of freedom that are exploited to meet environmental challenges, and to modify the evolutionary process itself. Here we use automata chemistry models and spatial RNA world models to study the emergence of parasitism and the complexity that evolves in response. The system is initialised with a hand-designed replicator that copies other replicators with a small chance of point mutation. Almost immediately, short parasites arise; these are copied more quickly, and so have an evolutionary advantage. The replicators also become shorter, and so are replicated faster; they evolve a mechanism to slow down replication, which reduces the difference of replication rate of replicators and parasites. They also evolve explicit mechanisms to discriminate copies of self from parasites; these mechanisms become increasingly complex. New parasite species continually arise from mutated replicators, rather than from evolving parasite lineages. Evolution itself evolves, eg by effectively increasing point mutation rates, and by generating novel emergent mutational operators. Thus, parasitism drives the evolution of complex replicators and complex ecosystems.

evolutionary biology↗

bioRxiv2020

Bacteria maintain Slightly Beneficial Genes and Selfish Genetic Elements through the evolution of Horizontal Gene Transfer

Horizontal gene transfer (HGT) is a key component of bacterial evolution, which in concert with gene loss can result in rapid changes in gene content. While HGT can evidently aid bacteria to adapt to new environments, it also carries risks since bacteria may pick up selfish genetic elements (SGEs). Here, we use modeling to study how bacterial growth rates are affected by HGT of slightly beneficial genes, if bacteria can evolve HGT to improve their growth rates, and when HGT is evolutionarily maintained in light of harmful SGEs. We find that we can distinguish between four classes of slightly beneficial genes: indispensable, enrichable, rescuable, and unrescuable genes. Rescuable genes - genes that confer small fitness benefits and are lost from the population in the absence of HGT -- can be collectively retained by a bacterial community that engages in HGT. While this gene-sharing cannot evolve in well-mixed cultures, it does evolve in a spatially structured population such as a biofilm. Although HGT does indeed enable infection by harmful SGEs, HGT is nevertheless evolutionarily maintained by the hosts, explaining the stable coexistence and co-evolution of bacteria and SGEs.

microbiology↗

bioRxiv2019

Anticipation of a serial transfer protocol through the evolution of fine-tuned growth dynamics

BackgroundExperimental evolution of microbes often involves a serial transfer protocol, where microbes are repeatedly diluted by transfer to a fresh medium, starting a new growth cycle. This protocol has revealed that evolution can be remarkably reproducible, where microbes show parallel adaptations both on the level of the phenotype as well as the genotype. However, these studies also reveal a strong potential for divergent evolution, leading to diversity both between and within replicate populations. We here study how in silico evolved Virtual Microbe "wild types" (WTs) adapt to a serial transfer protocol to investigate both the generic evolutionary adaptation to such an environment which are independent of prior evolution, and the variety of ways in which the adaptation is implemented at the individual and ecosystem level. ResultsWe show that all pre-evolved WTs evolve to anticipate the regularity of the serial transfer protocol by adopting a fine-tuned balance of growth and survival. We find that this anticipation can be done in a variety of ways, either by a single lineage or by several lineages in consort. Interestingly, replicate populations of the same WT initially show similar trajectories, but may subsequently diverge along a growth rate versus yield trade-off. ConclusionsWe find that all our in silico WTs show the same anticipation effects -- fitting the periodicity of a serial transfer protocol -- but do so by a variety of mechanisms. Our results reveal new insights into the dynamics and relevant selection pressures in experimental evolution, but also highlight how, in an eco-evolutionary context, numerous mechanisms can evolve to the same end.

evolutionary biology↗