A Unifying Scenario on the Origin and Evolution of Cellular and Viral Domains

The cellular theory on the nature of life has been one of the first major advancements in biology. Viruses, however, are the most abundant life forms, and their exclusion from mainstream biology and the Tree of Life (TOL) is a major paradox in biology. This article presents a broad, unifying scenario on the origin and evolution of cellular and viral domains that challenges the conventional views about the history of life and supports a TOL that includes viruses. Co-evolution of viruses and their host cells has led to some of the most remarkable developments and transitions in the evolution of life, including the origin of non-coding DNA as a genomic protective device against viral insertion damage. However, one of the major fundamental evolutionary developments driven by viruses was probably the origin of cellular domains - Bacteria, Archaea and Eukarya - from the Last Universal Common Ancestor (LUCA) lineage, by evolving anti-fusion mechanisms. Consistent with a novel fusion/fission model for the population mode of evolution of LUCA, this paper presents a “cell-like world” model for the origin of life. According to this model the evolution of coupled replication, transcription and translation system (RT&T) occurred within non-living cell-like compartments (CCs). In this model, the ancestral ribosome originated as template-based RNA synthesizing machinery. The origin of the cellular genome as a centralized unit for storage and replication of genetic information within the CCs facilitated the evolution of the ancestral ribosome into a powerful translation machinery - the modern ribosome. After several hundred millions of years of providing an enclosed environment and fusion/fission based exchanges necessary for the population mode of evolution of the basic metabolism and the RT&T, the CCs evolved into the first living entities on earth - the LUCA lineage. The paper concludes with a proposal for a TOL that integrates the co-evolution of cellular and viral domains. This is one of a series of three articles that present a unifying scenario on the origin and evolution of viral and cellular domains, including the origin of life, which has significant t bio-medical implications and could lead to a significant paradigm shift in biology

Stem Cell Transplantation As A Dynamical System: Are Clinical Outcomes Deterministic?

Outcomes in stem cell transplantation (SCT) are modeled using probability theory. However the clinical course following SCT appears to demonstrate many characteristics of dynamical systems, especially when outcomes are considered in the context of immune reconstitution. Dynamical systems tend to evolve over time according to mathematically determined rules. Characteristically, the future states of the system are predicated on the states preceding them, and there is sensitivity to initial conditions. In SCT, the interaction between donor T cells and the recipient may be considered as such a system in which, graft source, conditioning and early immunosuppression profoundly influence immune reconstitution over time. This eventually determines clinical outcomes, either the emergence of tolerance or the development of graft versus host disease. In this paper parallels between SCT and dynamical systems are explored and a conceptual framework for developing mathematical models to understand disparate transplant outcomes is proposed.Comment: 23 pages, 4 figures. Updated version with additional data, 2 new figures and editorial revisions. New authors adde

Clonality and intracellular polyploidy in virus evolution and pathogenesis

In the present article we examine clonality in virus evolution. Most viruses retain an active recombination machinery as a potential means to initiate new levels of genetic exploration that go beyond those attainable solely by point mutations. However, despite abundant recombination that may be linked to molecular events essential for genome replication, herein we provide evidence that generation of recombinants with altered biological properties is not essential for the completion of the replication cycles of viruses, and that viral lineages (near-clades) can be defined. We distinguish mechanistically active but inconsequential recombination from evolutionarily relevant recombination, illustrated by episodes in the field and during experimental evolution. In the field, recombination has been at the origin of new viral pathogens, and has conferred fitness advantages to some viruses once the parental viruses have attained a sufficient degree of diversification by point mutations. In the laboratory, recombination mediated a salient genome segmentation of foot-and-mouth disease virus, an important animal pathogen whose genome in nature has always been characterized as unsegmented. We propose a model of continuous mutation and recombination, with punctuated, biologically relevant recombination events for the survival of viruses, both as disease agents and as promoters of cellular evolution. Thus, clonality is the standard evolutionary mode for viruses because recombination is largely inconsequential, since the decisive events for virus replication and survival are not dependent on the exchange of genetic material and formation of recombinant (mosaic) genomes.Work in Madrid is supported by Grants BFU-2011-23604 and P2013/ABI-2906 (PLATESA from Comunidad Autónoma de Madrid) and Fundación R. Areces; Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas is funded by Instituto de Salud Carlos III; E.M. is supported by a fellowship from Ministerio de Economía y Competitividad; and C.P. is supported by theMiguel Servet program of the FIS Instituto de Salud Carlos III (CP14/00121).Peer Reviewe

Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent Proechimys semispinosus.

Hepatitis delta virus (HDV) is a human hepatitis-causing RNA virus, unrelated to any other taxonomic group of RNA viruses. Its occurrence as a satellite virus of hepatitis B virus (HBV) is a singular case in animal virology for which no consensus evolutionary explanation exists. Here we present a mammalian deltavirus that does not occur in humans, identified in the neotropical rodent species Proechimys semispinosus The rodent deltavirus is highly distinct, showing a common ancestor with a recently described deltavirus in snakes. Reverse genetics based on a tandem minus-strand complementary DNA genome copy under the control of a cytomegalovirus (CMV) promoter confirms autonomous genome replication in transfected cells, with initiation of replication from the upstream genome copy. In contrast to HDV, a large delta antigen is not expressed and the farnesylation motif critical for HBV interaction is absent from a genome region that might correspond to a hypothetical rodent large delta antigen. Correspondingly, there is no evidence for coinfection with an HBV-related hepadnavirus based on virus detection and serology in any deltavirus-positive animal. No other coinfecting viruses were detected by RNA sequencing studies of 120 wild-caught animals that could serve as a potential helper virus. The presence of virus in blood and pronounced detection in reproductively active males suggest horizontal transmission linked to competitive behavior. Our study establishes a nonhuman, mammalian deltavirus that occurs as a horizontally transmitted infection, is potentially cleared by immune response, is not focused in the liver, and possibly does not require helper virus coinfection

Simulation of immune system response to bacterial challenge

Immune system (IS) simulations have several applications, such as biological theory testing or as a complement in the development of improved drugs. This paper presents an agent based approach to simulate the IS response to bacterial infection challenge. The agent simulator is implemented in a discrete time and twodimensional space, and composed by two layers: a) a specialized cellular automata responsible for substance di usion and reactions; and b) the layer where agents move, act and interact. The IS model focuses upon low level cellular receptor interactions, receptor diversity and genetic-ruled agents, aiming to observe and study the resultant emergent behavior. The model reproduces the following IS behavioral characteristics: speci city and specialization, immune memory and vaccine immunization

Proliferating active matter

The fascinating patterns of collective motion created by autonomously driven particles have fuelled active-matter research for over two decades. So far, theoretical active-matter research has often focused on systems with a fixed number of particles. This constraint imposes strict limitations on what behaviours can and cannot emerge. However, a hallmark of life is the breaking of local cell number conservation by replication and death. Birth and death processes must be taken into account, for example, to predict the growth and evolution of a microbial biofilm, the expansion of a tumour, or the development from a fertilized egg into an embryo and beyond. In this Perspective, we argue that unique features emerge in these systems because proliferation represents a distinct form of activity: not only do the proliferating entities consume and dissipate energy, they also inject biomass and degrees of freedom capable of further self-proliferation, leading to myriad dynamic scenarios. Despite this complexity, a growing number of studies document common collective phenomena in various proliferating soft-matter systems. This generality leads us to propose proliferation as another direction of active-matter physics, worthy of a dedicated search for new dynamical universality classes. Conceptual challenges abound, from identifying control parameters and understanding large fluctuations and nonlinear feedback mechanisms to exploring the dynamics and limits of information flow in self-replicating systems. We believe that, by extending the rich conceptual framework developed for conventional active matter to proliferating active matter, researchers can have a profound impact on quantitative biology and reveal fascinating emergent physics along the way

The fractal urban coherence in biourbanism: the factual elements of urban fabric

This article is available online and will be inserted in also printed format in the Journal in October 2013.During the last few decades, modern urban fabric lost some very important elements, only because urban design and planning turned out to be stylistic aerial views or new landscapes of iconic technological landmarks. Biourbanism attempts to re-establish lost values and balance, not only in urban fabric, but also in reinforcing human-oriented design principles in either micro or macro scale. Biourbanism operates as a catalyst of theories and practices in both architecture and urban design to guarantee high standards in services, which are currently fundamental to the survival of communities worldwide. Human life in cities emerges during connectivity via geometrical continuity of grids and fractals, via path connectivity among highly active nodes, via exchange/movement of people and, finally via exchange of information (networks). In most human activities taking place in central areas of cities, people often feel excluded from design processes in the built environment. This paper aims at exploring the reasons for which, fractal cities, which have being conceived as symmetries and patterns, can have scientifically proven and beneficial impact on human fitness of body and mind; research has found that, brain traumas caused by visual agnosia become evident when patterns disappear from either 2D or 3D emergences in architectural and urban design.ADT Fund

Emergent networks in immune system shape space

The development of a computational model is reported which facilitates the study of emergent principles of human immune system effector T cell clonotype repertoire and its distribution and differentiation. In particular, the question of systemic self-organisation is addressed. The model represents an extension to earlier immune system shape space formalism, such that each activated effector T cell clonotype and respective immunogenic viral epitope is represented as a node in a two-dimensional network space, and edges between nodes models the affinity and clearance pressure applied to the antigen presenting cell bearing the target epitope. As the model is repeatedly exposed to infection by heterologous or mutating viruses, a distinct topology of the network shape space emerges which may offer a theoretical explanation of recent biological experimental results in the field of murine (mouse) cytotoxic T cell activation, apoptosis, crossreactivity, and memory - especially with respect to repeated reinfection. In the past, most discrete computational models of immune response to vira l infections have used separate real space or shape space formalisms. In this work, however, we have developed a model based on a combination of the two, with the objective of demonstrating how emergent behaviour and principles of self organisation may arise from a many-particle microscopic system. This is achieved by using a stochastic model of the lymphatic system as stimulus to a networ