Gergely J. Szollosi

Phase transition in the collective migration of tissue cells: Experiment and model

We have recorded the swarming-like collective migration of a large number of keratocytes (tissue cells obtained from the scales of goldfish) using long-term videomicroscopy. By increasing the overall density of the migrating cells, we have been able to demonstrate experimentally a kinetic phase transition from a disordered into an ordered state. Near the critical density a complex picture emerges with interacting clusters of cells moving in groups. Motivated by these experiments we have constructed a flocking model that exhibits a continuous transition to the ordered phase, while assuming only short-range interactions and no explicit information about the knowledge of the directions of motion of neighbors. Placing cells in microfabricated arenas we found spectacular whirling behavior which we could also reproduce in simulations.

Damage and fluctuations induce loops in optimal transport networks.

Leaf venation is a pervasive example of a complex biological network, endowing leaves with a transport system and mechanical resilience. Transport networks optimized for efficiency have been shown to be trees, i.e., loopless. However, dicotyledon leaf venation has a large number of closed loops, which are functional and able to transport fluid in the event of damage to any vein, including the primary veins. Inspired by leaf venation, we study two possible reasons for the existence of a high density of loops in transport networks: resilience to damage and fluctuations in load. In the first case, we seek the optimal transport network in the presence of random damage by averaging over damage to each link. In the second case, we seek the network that optimizes transport when the load is sparsely distributed: at any given time most sinks are closed. We find that both criteria lead to the presence of loops in the optimum state.

An efficient algorithm for gene/species trees parsimonious reconciliation with losses, duplications and transfers

Tree reconciliation methods aim at estimating the evolutionary events that cause discrepancy between gene trees and species trees. We provide a discrete computational model that considers duplications, transfers and losses of genes. The model yields a fast and exact algorithm to infer time consistent and most parsimonious reconciliations. Then we study the conditions under which parsimony is able to accurately infer such events. Overall, it performs well even under realistic rates, transfers being in general less accurately recovered than duplications. An implementation is freely available at http://www.atgc-montpellier.fr/MPR.

Phylogenetic modeling of lateral gene transfer reconstructs the pattern and relative timing of speciations.

The timing of the evolution of microbial life has largely remained elusive due to the scarcity of prokaryotic fossil record and the confounding effects of the exchange of genes among possibly distant species. The history of gene transfer events, however, is not a series of individual oddities; it records which lineages were concurrent and thus provides information on the timing of species diversification. Here, we use a probabilistic model of genome evolution that accounts for differences between gene phylogenies and the species tree as series of duplication, transfer, and loss events to reconstruct chronologically ordered species phylogenies. Using simulations we show that we can robustly recover accurate chronologically ordered species phylogenies in the presence of gene tree reconstruction errors and realistic rates of duplication, transfer, and loss. Using genomic data we demonstrate that we can infer rooted species phylogenies using homologous gene families from complete genomes of 10 bacterial and archaeal groups. Focusing on cyanobacteria, distinguished among prokaryotes by a relative abundance of fossils, we infer the maximum likelihood chronologically ordered species phylogeny based on 36 genomes with 8,332 homologous gene families. We find the order of speciation events to be in full agreement with the fossil record and the inferred phylogeny of cyanobacteria to be consistent with the phylogeny recovered from established phylogenomics methods. Our results demonstrate that lateral gene transfers, detected by probabilistic models of genome evolution, can be used as a source of information on the timing of evolution, providing a valuable complement to the limited prokaryotic fossil record.

Emergent Neutrality in Adaptive Asexual Evolution

In nonrecombining genomes, genetic linkage can be an important evolutionary force. Linkage generates interference interactions, by which simultaneously occurring mutations affect each other’s chance of fixation. Here, we develop a comprehensive model of adaptive evolution in linked genomes, which integrates interference interactions between multiple beneficial and deleterious mutations into a unified framework. By an approximate analytical solution, we predict the fixation rates of these mutations, as well as the probabilities of beneficial and deleterious alleles at fixed genomic sites. We find that interference interactions generate a regime of emergent neutrality: all genomic sites with selection coefficients smaller in magnitude than a characteristic threshold have nearly random fixed alleles, and both beneficial and deleterious mutations at these sites have nearly neutral fixation rates. We show that this dynamic limits not only the speed of adaptation, but also a population’s degree of adaptation in its current environment. We apply the model to different scenarios: stationary adaptation in a time-dependent environment and approach to equilibrium in a fixed environment. In both cases, the analytical predictions are in good agreement with numerical simulations. Our results suggest that interference can severely compromise biological functions in an adapting population, which sets viability limits on adaptive evolution under linkage.

Integrative modeling of gene and genome evolution roots the archaeal tree of life

Significance The Archaea represent a primary domain of cellular life, play major roles in modern-day biogeochemical cycles, and are central to debates about the origin of eukaryotic cells. However, understanding their origins and evolutionary history is challenging because of the immense time spans involved. Here we apply a new approach that harnesses the information in patterns of gene family evolution to find the root of the archaeal tree and to resolve the metabolism of the earliest archaeal cells. Our approach robustly distinguishes between published rooting hypotheses, suggests that the first Archaea were anaerobes that may have fixed carbon via the Wood–Ljungdahl pathway, and quantifies the cumulative impact of horizontal transfer on archaeal genome evolution. A root for the archaeal tree is essential for reconstructing the metabolism and ecology of early cells and for testing hypotheses that propose that the eukaryotic nuclear lineage originated from within the Archaea; however, published studies based on outgroup rooting disagree regarding the position of the archaeal root. Here we constructed a consensus unrooted archaeal topology using protein concatenation and a multigene supertree method based on 3,242 single gene trees, and then rooted this tree using a recently developed model of genome evolution. This model uses evidence from gene duplications, horizontal transfers, and gene losses contained in 31,236 archaeal gene families to identify the most likely root for the tree. Our analyses support the monophyly of DPANN (Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, Nanohaloarchaea), a recently discovered cosmopolitan and genetically diverse lineage, and, in contrast to previous work, place the tree root between DPANN and all other Archaea. The sister group to DPANN comprises the Euryarchaeota and the TACK Archaea, including Lokiarchaeum, which our analyses suggest are monophyletic sister lineages. Metabolic reconstructions on the rooted tree suggest that early Archaea were anaerobes that may have had the ability to reduce CO2 to acetate via the Wood–Ljungdahl pathway. In contrast to proposals suggesting that genome reduction has been the predominant mode of archaeal evolution, our analyses infer a relatively small-genomed archaeal ancestor that subsequently increased in complexity via gene duplication and horizontal gene transfer.

Gene Acquisitions from Bacteria at the Origins of Major Archaeal Clades Are Vastly Overestimated

In a recent article, Nelson-Sathi et al. (NS) report that the origins of major archaeal lineages (MAL) correspond to massive group-specific gene acquisitions via HGT from bacteria (Nelson-Sathi et al. 2015. Origins of major archaeal clades correspond to gene acquisitions from bacteria. Nature 517(7532):77-80.). If correct, this would have fundamental implications for the process of diversification in microbes. However, a reexamination of these data and results shows that the methodology used by NS systematically inflates the number of genes acquired at the root of each MAL, and incorrectly assumes bacterial origins for these genes. A reanalysis of their data with appropriate phylogenetic models accounting for the dynamics of gene gain and loss between lineages supports the continuous acquisition of genes over long periods in the evolution of Archaea.

The effect of recombination on the neutral evolution of genetic robustness

Conventional population genetics considers the evolution of a limited number of genotypes corresponding to phenotypes with different fitness. As model phenotypes, in particular RNA secondary structure, have become computationally tractable, however, it has become apparent that the context dependent effect of mutations and the many-to-one nature inherent in these genotype-phenotype maps can have fundamental evolutionary consequences. It has previously been demonstrated that populations of genotypes evolving on the neutral networks corresponding to all genotypes with the same secondary structure only through neutral mutations can evolve mutational robustness [E. van Nimwegen, J.P. Crutchfield, M. Huynen, Neutral evolution of mutational robustness, Proc. Natl. Acad. Sci. USA 96(17), 9716-9720 (1999)], by concentrating the population on regions of high neutrality. Introducing recombination we demonstrate, through numerically calculating the stationary distribution of an infinite population on ensembles of random neutral networks that mutational robustness is significantly enhanced and further that the magnitude of this enhancement is sensitive to details of the neutral network topology. Through the simulation of finite populations of genotypes evolving on random neutral networks and a scaled down microRNA neutral network, we show that even in finite populations recombination will still act to focus the population on regions of locally high neutrality.

The maintenance of sex in bacteria is ensured by its potential to reload genes

Why sex is maintained in nature is a fundamental question in biology. Natural genetic transformation (NGT) is a sexual process by which bacteria actively take up exogenous DNA and use it to replace homologous chromosomal sequences. As it has been demonstrated, the role of NGT in repairing deleterious mutations under constant selection is insufficient for its survival, and the lack of other viable explanations have left no alternative except that DNA uptake provides nucleotides for food. Here we develop a novel simulation approach for the long-term dynamics of genome organization (involving the loss and acquisition of genes) in a bacterial species consisting of a large number of spatially distinct populations subject to independently fluctuating ecological conditions. Our results show that in the presence of weak interpopulation migration NGT is able to subsist as a mechanism to reload locally lost, intermittently selected genes from the collective gene pool of the species through DNA uptake from migrants. Reloading genes and combining them with those in locally adapted genomes allow individual cells to readapt faster to environmental changes. The machinery of transformation survives under a wide range of model parameters readily encompassing real-world biological conditions. These findings imply that the primary role of NGT is not to serve the cell with food, but to provide homologous sequences for restoring genes that have disappeared from or become degraded in the local population.

The relevance of neck linker docking in the motility of kinesin

Conventional kinesin is a motor protein, which is able to walk along a microtubule processively. The exact mechanism of the stepping motion and force generation of kinesin is still far from clear. In this paper we argue that neck linker docking is a crucial element of this mechanism, without which the experimentally observed dwell times of the steps could not be explained under a wide range of loading forces. We also show that the experimental data impose very strict constraints on the lengths of both the neck linker and its docking section, which are compatible with the known structure of kinesin.