scholarly journals Novelty by Furcation and Fusion: How tree-like is evolution?

2017 ◽  
Author(s):  
Todd H. Oakley
Keyword(s):  
Phylogenetic Trees ◽  
Evolutionary History ◽  
Cell Types ◽  
Phylogenetic Networks ◽  
Phylogenetic Study ◽  
Type Model ◽  
Cell Type ◽  
Biological Organization ◽  
Vertical Inheritance ◽  
Different Levels

AbstractNovelty and innovation are fundamental yet relatively understudied concepts in evolution. We may study novelty phylogenetically, with a key question of whether evolution occurs by tree-like branching, or through exchange of distantly related parts in processes akin to horizontal transfer. Here, I argue that except at the lowest levels of biological organization, evolution is not usually tree-like. Perfectly vertical inheritance, an assumption of evolutionary trees, requires simultaneous co-duplication of all the parts of a duplicating or speciating (which I collectively call 'furcating') biological feature. However, simultaneous co-duplication of many parts usually requires variational processes that are rare. Therefore, instead of being perfectly tree-like, evolution often involves events that incorporate or fuse more distantly related parts into new units during evolution, which herein I call 'fusion'. Exon shuffling, horizontal gene transfer, introgression and co-option are such fusion processes at different levels of organization. In addition to co-duplication, units under phylogenetic study must individuate (gaining evolutionary independence) before they can diverge. A lack of individuation erases evolutionary history, and provides another challenge to tree-like evolution. In particular, biological units in the same organism that are the products of development always share the same genome, perhaps making full individuation difficult. The ubiquity of processes that fuse distantly related parts or oppose individuation has wide ranging implications for the study of macroevolution. For one, the central metaphor of a tree of life will often be violated, to the point where we may need a different metaphor, such as economic public goods, or a ‘web of life’. Secondly, we may need to expand current models. For example, even under the prevailing model of cell-type evolution, the sister-cell-type model, a lack of complete individuation and evolution by co-option will often be involved in forming new cell-types. Finally, these processes highlight a need for an expansive toolkit for studying evolutionary history. Multivariate methods are particularly critical to discover co-variation, the hallmark of an absence of complete individuation. In addition to studying phylogenetic trees, we may often need to analyze and visualize phylogenetic networks. Even though furcation - the splitting and individuation of biological features - does happen, fusion of distant events is just as critical for the evolution of novelties, and must formally be incorporated into the metaphors, models, and visualization of evolutionary history.

Varied interactions between proviruses and adjacent host chromatin

1986 ◽  
Vol 6 (11) ◽  
pp. 3999-4007
Author(s):  
K F Conklin ◽  
M Groudine
Keyword(s):  
Cell Types ◽  
Chromatin Conformation ◽  
Cell Type ◽  
Chromatin Domains ◽  
Site Structure ◽  
The Relationship ◽  
Structure And Activity ◽  
Different Levels ◽  
Host Chromatin ◽  
Nuclease Sensitivity

Retroviruses integrated at unique locations in the host genome can be expressed at different levels. We have analyzed the preintegration sites of three transcriptionally competent avian endogenous proviruses (evs) to determine whether the various levels of provirus expression correlate with their location in active or inactive regions of chromatin. Our results show that in three of four cell types, the chromatin conformation (as defined by relative nuclease sensitivity) of virus preintegration sites correlates with the level of expression of the resident provirus in ev+ cells: two inactive proviruses (ev-1 and ev-2) reside in nuclease-resistant chromatin domains and one active provirus (ev-3) resides in a nuclease-sensitive domain. Nuclear runoff transcription assays reveal that the preintegration sites of the active and inactive viruses are not transcribed. However, in erythrocytes of 15-day-old chicken embryos (15d RBCs), the structure and activity of the ev-3 provirus is independent of the conformation of its preintegration site. In this cell type, the ev-3 preintegration site is organized in a nuclease-resistant conformation, while the ev-3 provirus is in a nuclease-sensitive conformation and is transcribed. In addition, the nuclease sensitivity of host sequences adjacent to ev-3 is altered in ev-3+ 15d RBCs relative to that found in 15d RBCs that lack ev-3. These data suggest that the relationship between preintegration site structure and retrovirus expression is more complex than previously described.

scholarly journals Population-based mechanistic modeling allows for quantitative predictions of drug responses across cell types

2017 ◽  
Author(s):  
Jingqi QX Gong ◽  
Eric A Sobie
Keyword(s):  
Pluripotent Stem Cells ◽  
Cardiac Electrophysiology ◽  
Cell Types ◽  
Population Based ◽  
Experimental Models ◽  
Mechanistic Modeling ◽  
Type Model ◽  
Cell Type ◽  
Drug Responses ◽  
Induced Pluripotent

ABSTRACTQuantitative mismatches between human physiology and experimental models can present serious limitations for the development of effective therapeutics. We addressed this issue, in the context of cardiac electrophysiology, through mechanistic mathematical modeling combined with statistical analyses. Physiological metrics were simulated in heterogeneous populations describing cardiac myocytes from adult ventricles and those derived from induced pluripotent stem cells (iPSC-CMs). These simulated measures were used to construct a cross-cell type regression model that predicts adult myocyte drug responses from iPSC-CM behaviors. We found that quantitatively accurate predictions of responses to selective or non-selective drugs could be generated based on iPSC-CM responses and that the method can be extended to predict drug responses in diseased as well as healthy cells. This cross-cell type model can be of great value in drug development, and the approach, which can be applied to other fields, represents an important strategy for overcoming experimental model limitations.

scholarly journals Applicability of several rooted phylogenetic network algorithms for representing the evolutionary history of SARS-CoV-2

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rosanne Wallin ◽  
Leo van Iersel ◽  
Steven Kelk ◽  
Leen Stougie
Keyword(s):  
Phylogenetic Trees ◽  
Evolutionary History ◽  
Network Inference ◽  
Phylogenetic Network ◽  
Phylogenetic Networks ◽  
Network Algorithms ◽  
Running Time ◽  
Inference Algorithms ◽  
History Of ◽  
The Impact

Abstract Background Rooted phylogenetic networks are used to display complex evolutionary history involving so-called reticulation events, such as genetic recombination. Various methods have been developed to construct such networks, using for example a multiple sequence alignment or multiple phylogenetic trees as input data. Coronaviruses are known to recombine frequently, but rooted phylogenetic networks have not yet been used extensively to describe their evolutionary history. Here, we created a workflow to compare the evolutionary history of SARS-CoV-2 with other SARS-like viruses using several rooted phylogenetic network inference algorithms. This workflow includes filtering noise from sets of phylogenetic trees by contracting edges based on branch length and bootstrap support, followed by resolution of multifurcations. We explored the running times of the network inference algorithms, the impact of filtering on the properties of the produced networks, and attempted to derive biological insights regarding the evolution of SARS-CoV-2 from them. Results The network inference algorithms are capable of constructing rooted phylogenetic networks for coronavirus data, although running-time limitations require restricting such datasets to a relatively small number of taxa. Filtering generally reduces the number of reticulations in the produced networks and increases their temporal consistency. Taxon bat-SL-CoVZC45 emerges as a major and structural source of discordance in the dataset. The tested algorithms often indicate that SARS-CoV-2/RaTG13 is a tree-like clade, with possibly some reticulate activity further back in their history. A smaller number of constructed networks posit SARS-CoV-2 as a possible recombinant, although this might be a methodological artefact arising from the interaction of bat-SL-CoVZC45 discordance and the optimization criteria used. Conclusion Our results demonstrate that as part of a wider workflow and with careful attention paid to running time, rooted phylogenetic network algorithms are capable of producing plausible networks from coronavirus data. These networks partly corroborate existing theories about SARS-CoV-2, and partly produce new avenues for exploration regarding the location and significance of reticulate activity within the wider group of SARS-like viruses. Our workflow may serve as a model for pipelines in which phylogenetic network algorithms can be used to analyse different datasets and test different hypotheses.

scholarly journals Varied interactions between proviruses and adjacent host chromatin.

1986 ◽  
Vol 6 (11) ◽  
pp. 3999-4007 ◽  
Author(s):  
K F Conklin ◽  
M Groudine
Keyword(s):  
Cell Types ◽  
Chromatin Conformation ◽  
Cell Type ◽  
Chromatin Domains ◽  
Site Structure ◽  
The Relationship ◽  
Structure And Activity ◽  
Different Levels ◽  
Host Chromatin ◽  
Nuclease Sensitivity

Retroviruses integrated at unique locations in the host genome can be expressed at different levels. We have analyzed the preintegration sites of three transcriptionally competent avian endogenous proviruses (evs) to determine whether the various levels of provirus expression correlate with their location in active or inactive regions of chromatin. Our results show that in three of four cell types, the chromatin conformation (as defined by relative nuclease sensitivity) of virus preintegration sites correlates with the level of expression of the resident provirus in ev+ cells: two inactive proviruses (ev-1 and ev-2) reside in nuclease-resistant chromatin domains and one active provirus (ev-3) resides in a nuclease-sensitive domain. Nuclear runoff transcription assays reveal that the preintegration sites of the active and inactive viruses are not transcribed. However, in erythrocytes of 15-day-old chicken embryos (15d RBCs), the structure and activity of the ev-3 provirus is independent of the conformation of its preintegration site. In this cell type, the ev-3 preintegration site is organized in a nuclease-resistant conformation, while the ev-3 provirus is in a nuclease-sensitive conformation and is transcribed. In addition, the nuclease sensitivity of host sequences adjacent to ev-3 is altered in ev-3+ 15d RBCs relative to that found in 15d RBCs that lack ev-3. These data suggest that the relationship between preintegration site structure and retrovirus expression is more complex than previously described.

scholarly journals Phylogenetic Trees and Networks Can Serve as Powerful and Complementary Approaches for Analysis of Genomic Data

2019 ◽  
Vol 69 (3) ◽  
pp. 593-601 ◽  
Author(s):  
Christopher Blair ◽  
Cécile Ané
Keyword(s):  
Gene Flow ◽  
Phylogenetic Trees ◽  
Evolutionary History ◽  
Incomplete Lineage Sorting ◽  
Gene Tree ◽  
Phylogenetic Network ◽  
Genomic Data ◽  
Point Of View ◽  
Phylogenetic Networks ◽  
Lineage Sorting

Abstract Genomic data have had a profound impact on nearly every biological discipline. In systematics and phylogenetics, the thousands of loci that are now being sequenced can be analyzed under the multispecies coalescent model (MSC) to explicitly account for gene tree discordance due to incomplete lineage sorting (ILS). However, the MSC assumes no gene flow post divergence, calling for additional methods that can accommodate this limitation. Explicit phylogenetic network methods have emerged, which can simultaneously account for ILS and gene flow by representing evolutionary history as a directed acyclic graph. In this point of view, we highlight some of the strengths and limitations of phylogenetic networks and argue that tree-based inference should not be blindly abandoned in favor of networks simply because they represent more parameter rich models. Attention should be given to model selection of reticulation complexity, and the most robust conclusions regarding evolutionary history are likely obtained when combining tree- and network-based inference.

scholarly journals Comparing the topology of phylogenetic network generators

2021 ◽  
Author(s):  
Remie Janssen ◽  
Pengyu Liu
Keyword(s):  
Bayesian Methods ◽  
Phylogenetic Trees ◽  
Evolutionary History ◽  
Phylogenetic Network ◽  
Random Trees ◽  
Phylogenetic Networks ◽  
Phylogeny Reconstruction ◽  
Evolutionary Analysis ◽  
Summary Statistics ◽  
History Of

Phylogenetic networks represent evolutionary history of species and can record natural reticulate evolutionary processes such as horizontal gene transfer and gene recombination. This makes phylogenetic networks a more comprehensive representation of evolutionary history compared to phylogenetic trees. Stochastic processes for generating random trees or networks are important tools in evolutionary analysis, especially in phylogeny reconstruction where they can be utilized for validation or serve as priors for Bayesian methods. However, as more network generators are developed, there is a lack of discussion or comparison for different generators. To bridge this gap, we compare a set of phylogenetic network generators by profiling topological summary statistics of the generated networks over the number of reticulations and comparing the topological profiles.

scholarly journals Reproducibility and reusability limitations in Regulatory Circuits: analysis and solutions

2021 ◽  
Author(s):  
Marine Louarn ◽  
Anne Siegel ◽  
Thierry Fest ◽  
Olivier Dameron ◽  
Fabrice Chatonnet
Keyword(s):  
Data Integration ◽  
Regulatory Networks ◽  
Cell Types ◽  
Biological Data ◽  
Google Scholar ◽  
Cell Type ◽  
Regulatory Circuits ◽  
Cell Type Specific ◽  
Different Levels

The Regulatory Circuits project is among the most recent and the most complete attempts to identify cell-type specific regulatory networks in Human. It is one of the largest efforts of public genomics data integration, based on data from the major consortia FANTOM5, ENCODE and Roadmap Epigenomics. This project is a main provider of biological data, cited more than 224 times (Google Scholar) and its resulting networks were used in at least 42 other articles. For such a general resource, reproducibility of both the outputs (regulation networks) and methods (data integration pipeline) is a major issue, since biological data are updated regularly. In addition, users may want to introduce new data into the Regulatory Circuits framework to provide networks about previously uncharacterized cell types or to add information about specific regulators, which require to re-execute the whole pipeline on the new data. In this article, we analyze the various factors limiting reproducibility of the Regulatory Circuits data and methods. Starting from a factual description of our understanding of the methods used in Regulatory Circuits, our contribution is two-fold: we propose (1) a characterization of the different levels of reusability, reproducibility and conceptual issues in the original workflow and (2) a new implementation of the workflow ensuring its consistency with the published description and allowing for an easier reuse and reproduction of the published outputs. Both are applicable beyond the case of Regulatory Circuits.

Dendritic cells of the human epidermis: immuno-electron microscopic studies of la antigen reactivity

1978 ◽  
Vol 36 (2) ◽  
pp. 644-645
Author(s):  
G. Rowden ◽  
M. G. Lewis ◽  
T. M. Phillips
Keyword(s):  
Dendritic Cells ◽  
Langerhans Cells ◽  
Cell Types ◽  
Cell Type ◽  
Electron Microscopic ◽  
La Antigen ◽  
Microscopic Studies ◽  
A Cell ◽  
C3 Receptors ◽  
Antigen Reactivity

Langerhans cells of mammalian stratified squamous epithelial have proven to be an enigma since their discovery in 1868. These dendritic suprabasal cells have been considered as related to melanocytes either as effete cells, or as post divisional products. Although grafting experiments seemed to demonstrate the independence of the cell types, much confusion still exists. The presence in the epidermis of a cell type with morphological features seemingly shared by melanocytes and Langerhans cells has been especially troublesome. This so called "indeterminate", or " -dendritic cell" lacks both Langerhans cells granules and melanosomes, yet it is clearly not a keratinocyte. Suggestions have been made that it is related to either Langerhans cells or melanocyte. Recent studies have unequivocally demonstrated that Langerhans cells are independent cells with immune function. They display Fc and C3 receptors on their surface as well as la (immune region associated) antigens.

scholarly journals Biochemical and phylogenetic networks-II: X-trees and phylogenetic trees

2021 ◽  
Vol 59 (3) ◽  
pp. 699-718
Author(s):  
R. Sundara Rajan ◽  
A. Arul Shantrinal ◽  
K. Jagadeesh Kumar ◽  
T. M. Rajalaxmi ◽  
Indra Rajasingh ◽  
...  
Keyword(s):  
Phylogenetic Trees ◽  
Phylogenetic Networks

scholarly journals Fibroblasts Influence the Efficacy, Resistance, and Future Use of Vaccines and Immunotherapy in Cancer Treatment

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 634
Author(s):  
Bailee H. Sliker ◽  
Paul M. Campbell
Keyword(s):  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Fibroblast Activation Protein ◽  
Cancer Associated Fibroblasts ◽  
Cell Type ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
New Research ◽  
Tumor Types

Tumors are composed of not only epithelial cells but also many other cell types that contribute to the tumor microenvironment (TME). Within this space, cancer-associated fibroblasts (CAFs) are a prominent cell type, and these cells are connected to an increase in tumor progression as well as alteration of the immune landscape present in and around the tumor. This is accomplished in part by their ability to alter the presence of both innate and adaptive immune cells as well as the release of various chemokines and cytokines, together leading to a more immunosuppressive TME. Furthermore, new research implicates CAFs as players in immunotherapy response in many different tumor types, typically by blunting their efficacy. Fibroblast activation protein (FAP) and transforming growth factor β (TGF-β), two major CAF proteins, are associated with the outcome of different immunotherapies and, additionally, have become new targets themselves for immune-based strategies directed at CAFs. This review will focus on CAFs and how they alter the immune landscape within tumors, how this affects response to current immunotherapy treatments, and how immune-based treatments are currently being harnessed to target the CAF population itself.

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