Biology subjects

Szollosi, G. J.

Publications and source records attributed to Szollosi, G. J..

11 recordsLinked to original sources

bioRxiv2025

Phylogenetic reconciliation supports a methanogenic ancestor of the Archaea and a derived origin for host-associated lineages

The phylogeny of the Archaea continues to be revisited and revised as new groups are discovered and phylogenetic methods improve, but key questions about their early evolution remain. It has been suggested that the root of the Archaea may lie on, or potentially within, any of three major groups - the Euryarchaeota, TACK+Asgard clade, and DPANN, the last of which includes many host-associated and genome-reduced lineages. These root hypotheses make starkly different predictions about the nature of early archaeal evolution: for example, a root on or within DPANN might suggest a small-genome and host-associated ancestor, with methanogenesis, the hallmark metabolism of the Archaea, evolving later. Here, we investigate the position of the archaeal root and the nature of the last archaeal common ancestor using a range of phylogenetic approaches, including the best available site- and branch-heterogeneous substitution models, and new gene tree-species tree reconciliation models that capture changes in rates of gene duplication, loss and transfer across the phylogeny. Our analyses converge on a narrow archaeal root region at/near the base of the Euryarchaeota, supporting hypotheses in which the Last Archaeal Common Ancestor (LACA) was a complex, free-living (hyper-)thermophilic methanogen. We recover DPANN as the sister group to TACK and Asgard archaea, and suggest that their genome evolution has been characterised by episodes of genome streamlining and expansion, driven by gene loss and transfer.

evolutionary biology↗

bioRxiv2025

Convergent genomic responses of human gut bacteria to variations in industrialization

To what extent gut bacteria respond to the distinct ecological pressures imposed by human lifestyle remains unclear. Here, we investigate how genomic adaptation in gut bacteria differ between industrialized and non-industrialized human populations. We generated a broad collection of isolate genomes spanning diverse host geographies, lifestyles, species, and strains. We first found that compared to MAGs, paired isolate genomes recover more functional elements and signals of horizontal gene transfers (HGTs). Leveraging isolate genomes from multiple species, we find that strains from industrialized hosts experience an expansion of proteome size and harbor greater pangenome fluidity, driven by recent events of HGTs. Gene- and variant-level analyses reveal convergent patterns of lifestyle-specific adaptation in functions that are critical for ecological adaptation, such as stress response, cell envelope remodeling and central metabolism. Our results demonstrate that industrialization imprints evolutionary signatures on gut bacterial genomes, illuminating the effects of rapidly changing environments on human biology.

evolutionary biology↗

bioRxiv2025

Phylogenomic analyses reveal that Panguiarchaeum is a clade of genome-reduced Asgard archaea

The Asgard archaea are a diverse archaeal phylum important for our understanding of cellular evolution because they include the lineage that gave rise to eukaryotes. Recent phylogenomic work has focused on characterising the diversity of Asgard archaea in an effort to identify the closest extant relatives of eukaryotes. However, resolving archaeal phylogeny is challenging, and the positions of two recently-described lineages - Njordarchaeales and Panguiarchaeales - are uncertain, in ways that directly bear on hypotheses of early evolution. In initial phylogenetic analyses, these lineages branched either with Asgards or with the distantly-related Korarchaeota, and it has been suggested that their genomes may be affected by metagenomic contamination. Resolving this debate is important because these clades include genome-reduced lineages that may help inform our understanding of the evolution of symbiosis within Asgard archaea. Here, we performed phylogenetic analyses revealing that the Njordarchaeales and Pangiuarchaeales constitute the new class Njordarchaeia within Asgard archaea. We found no evidence of metagenomic contamination affecting phylogenetic analyses. Njordarchaeia exhibit hallmarks of adaptations to (hyper-)thermophilic lifestyles, including biased sequence compositions that can induce phylogenetic artifacts unless adequately modelled. Panguiarchaeum is metabolically distinct from its relatives, with reduced metabolic potential and various auxotrophies. Phylogenetic reconciliation recovers a complex common ancestor of Asgard archaea that encoded the Wood-Ljungdahl pathway. The subsequent loss of this pathway during the reductive evolution of Panguiarchaeum may have been associated with the switch to a symbiotic lifestyle based on H2-syntrophy. Thus, Panguiarchaeum may contain the first obligate symbionts within Asgard archaea.

evolutionary biology↗

bioRxiv2023

ATP synthase evolution on a cross-braced dated tree of life

The timing of early cellular evolution from the divergence of Archaea and Bacteria to the origin of eukaryotes remains poorly constrained. The ATP synthase complex is thought to have originated prior to the Last Universal Common Ancestor (LUCA) and analyses of ATP synthase genes, together with ribosomes, have played a key role in inferring and rooting the tree of life. Here we reconstruct the evolutionary history of ATP synthases using an expanded sampling of Archaea, Bacteria, and eukaryotes. We developed a phylogenetic cross-bracing approach making use of endosymbioses and ancient gene duplications of the major ATP synthase subunits to infer a highly resolved, dated species tree and establish an absolute timeline for ATP synthase evolution. Our analyses show that the divergence of the ATP synthase into F- and A/V-type lineages, was a very early event in cellular evolution dating back to more than 4Ga potentially predating the diversification of Archaea and Bacteria. Our cross-braced, dated tree of life also provides insight into more recent evolutionary transitions including eukaryogenesis, showing that the eukaryotic nuclear and mitochondrial lineages diverged from their closest archaeal (2.67-2.19Ga) and bacterial (2.58-2.12Ga) relatives at roughly the same time, with the nuclear stem being moderately longer.

evolutionary biology↗

bioRxiv2023

The power and limitations of species tree-aware phylogenetics

Species tree-aware phylogenetic methods model how gene trees are generated along the species tree by a series of evolutionary events, including the duplication, transfer and loss of genes. Over the past ten years these methods have emerged as a powerful tool for inferring and rooting gene and species trees, inferring ancestral gene repertoires, and studying the processes of gene and genome evolution. However, these methods are complex and can be more difficult to use than traditional phylogenetic approaches. Method development is rapid, and it can be difficult to decide between approaches and interpret results. Here, we review ALE and GeneRax, two popular packages for reconciling gene and species trees, explaining how they work, how results can be interpreted, and providing a tutorial for practical analysis. It was recently suggested that reconciliation-based estimates of duplication and transfer frequencies are unreliable. We evaluate this criticism and find that, provided parameters are estimated from the data rather than being fixed based on prior assumptions, reconciliation-based inferences are in good agreement with the literature, recovering variation in gene duplication and transfer frequencies across lineages consistent with the known biology of studied clades. For example, published datasets support the view that transfers greatly outnumber duplications in most prokaryotic lineages. We conclude by discussing some limitations of current models and prospects for future progress. Significance statementEvolutionary trees provide a framework for understanding the history of life and organising biodiversity. In this review, we discuss some recent progress on statistical methods that allow us to combine information from many different genes within the framework of an overarching phylogenetic species tree. We review the advantages and uses of these methods and discuss case studies where they have been used to resolve deep branches within the tree of life. We conclude with the limitations of current methods and suggest how they might be overcome in the future.

evolutionary biology↗

bioRxiv2020

Relative time constraints improve molecular dating

Dating the tree of life is central to understanding the evolution of life on Earth. Molecular clocks calibrated with fossils represent the state of the art for inferring the ages of major groups. Yet, other information on the timing of species diversification can be used to date the tree of life. For example, horizontal gene transfer events and ancient coevolutionary relationships such as (endo)symbioses can imply temporal relationships between two nodes in a phylogeny (Davin et al. 2018). These alternative sources of temporal constraints can be particularly helpful when the geological record is sparse, e.g. for microorganisms, which represent the vast majority of extant and extinct biodiversity. Here, we present a new method to combine fossil calibrations and relative age constraints to estimate chronograms. We provide an implementation of relative age constraints in RevBayes (Hohna et al. 2016) that can be combined in a modular manner with the wide range of molecular dating methods available in the software. We use both realistic simulations and empirical datasets of 40 Cyanobacteria and 62 Archaea to evaluate our method. We show that the combination of relative age constraints with fossil calibrations significantly improves the estimation of node ages.

evolutionary biology↗

bioRxiv2020

Cancer Risk and the Somatic Cell Lineage Tree

All the cells of a multicellular organism are the product of cell divisions that trace out a single binary tree, the so-called cell lineage tree. Because cell divisions are accompanied by replication errors, the shape of the cell lineage tree is one of the key determinants of how somatic evolution, which can potentially lead to cancer, proceeds. Cancer initiation usually requires the accumulation of a certain number of driver mutations. By mapping the accumulation of driver mutations into a graph theoretical problem, we show that in leading order of the mutation rate the probability of collecting a given number of driver mutations depends only on the distribution of the lineage lengths (irrespective of any other details of the cell lineage tree), and we derive a simple analytical formula for this probability. Our results are crucial in understanding how natural selection can shape the cell lineage trees of multicellular organisms in order to reduce their lifetime risk of cancer. In particular, our results highlight the significance of the longest cell lineages. Our analytical formula also provides a tool to quantify cancer susceptibility in theoretical models of tissue development and maintenance, as well as for empirical data on cell linage trees. Significance StatementA series of cell divisions starting from a single cell produce and maintain tissues of multicellular organisms. Somatic evolution, including the development of cancer, takes place along the cell lineage tree traced out by these cell divisions. A fundamental question in cancer research is how the lifetime risk of cancer depends on the properties of an arbitrary cell lineage tree. Here we show that for small mutation rates (which is the case in reality) the distribution of the lineage lengths alone determines cancer risk, and that this risk can be described by a simple analytical formula. Our results have far-reaching implications not only for cancer research, but also for evolutionary biology in general.

evolutionary biology↗

bioRxiv2019

A compartment size-dependent selective threshold limits mutation accumulation in hierarchical tissues

Cancer is a genetic disease fueled by somatic evolution. Hierarchical tissue organization can slow somatic evolution by two qualitatively different mechanisms: by cell differentiation along the hierarchy "washing out" harmful mutations (Nowak et al. 2003, Werner et al. 2013) and by limiting the number of cell divisions required to maintain a tissue (Derenyi and Szoll[o] si 2017). Here we explore the effects of compartment size on somatic evolution in hierarchical tissues by considering cell number regulation that acts on cell division rates such that the number of cells in the tissue has the tendency to return to its desired homeostatic value. Introducing mutants with a proliferative advantage we demonstrate the existence of a third fundamental mechanism by which hierarchically organized tissues are able to slow down somatic evolution. We show that tissue size regulation leads to the emergence of a threshold proliferative advantage, below which mutants cannot persist. We find that the most significant determinant of the threshold selective advantage is compartment size, with the threshold being higher the smaller the compartment. Our results demonstrate that in sufficiently small compartments even mutations that confer substantial proliferative advantage cannot persist, but are expelled from the tissue by differentiation along the hierarchy. The resulting selective barrier can significantly slow down somatic evolution and reduce the risk of cancer by limiting the accumulation of mutations that increase the proliferation of cells. O_TEXTBOXSignificance StatementRenewed tissues of multicellular organism accumulate mutations that lead to ageing and cancer. To mitigate these effects self-renewing tissues produce cells along differentiation hierarchies, which have been shown to suppress somatic evolution both by limiting the number of cell divisions, and thus reducing mutational load, and by differentiation "washing out" mutations. Our analytical results reveal the existence of a third mechanism: a compartment size dependent threshold in proliferative advantage, below which mutations cannot persist, but are rapidly expelled from the tissue by differentiation. In sufficiently small compartments the resulting selective barrier can greatly slow down somatic evolution and reduce the risk of cancer by preventing the accumulation of mutations even if even they confer substantial proliferative advantage. C_TEXTBOX

evolutionary biology↗

bioRxiv2018

Zombi: A simulator of species, genes and genomes that accounts for extinct lineages.

SummaryHere we present Zombi, a tool to simulate the evolution of species, genomes and sequences in silico, that considers for the first time the evolution of genomes in extinct lineages. It also incorporates various features that have not to date been combined in a single simulator, such as the possibility of generating species trees with a pre-defined variation of speciation and extinction rates through time, simulating explicitly intergenic sequences of variable length and outputting gene tree - species tree reconciliations.\n\nAvailability and implementationSource code and manual are freely available in https://github.com/AADavin/ZOMBI/\n\nContactaaredav@gmail.com

bioinformatics↗

bioRxiv2017

Gene transfers, like fossils, can date the Tree of Life

Biodiversity has always been predominantly microbial and the scarcity of fossils from bacteria, archaea and microbial eukaryotes has prevented a comprehensive dating of the tree of life. Here we show that patterns of lateral gene transfer deduced from the analysis of modern genomes encode a novel and abundant source of information about the temporal coexistence of lineages throughout the history of life. We use new phylogenetic methods to reconstruct the history of thousands of gene families and demonstrate that dates implied by gene transfers are consistent with estimates from relaxed molecular clocks in Bacteria, Archaea and Eukaryotes. An inspection of discrepancies between transfers and clocks and a comparison with mammal fossils show that gene transfer in microbes is potentially as informative for dating the tree of life as the geological record in macroorganisms.

evolutionary biology↗

bioRxiv2017

Hierarchical tissue organization as a general mechanism to limit the accumulation of somatic mutations

How can tissues generate large numbers of cells, yet keep the divisional load (the number of divisions along cell lineages) low in order to curtail the accumulation of somatic mutations and reduce the risk of cancer? To answer the question we consider a general model of hierarchically organized self-renewing tissues and show that the lifetime divisional load of such a tissue is independent of the details of the cell differentiation processes, and depends only on two structural and two dynamical parameters. Our results demonstrate that a strict analytical relationship exists between two seemingly disparate characteristics of self-renewing tissues: divisional load and tissue organization. Most remarkably, we find that a sufficient number of progressively slower dividing cell types can be almost as efficient in minimizing the divisional load, as non-renewing tissues. We argue that one of the main functions of tissue-specific stem cells and differentiation hierarchies is the prevention of cancer.

cancer biology↗