The Uroboros Theory of Life’s Origin: 22-Nucleotide Theoretical Minimal RNA Rings Reflect Evolution of Genetic Code and tRNA-rRNA Translation Machineries Abstract Theoretical minimal RNA rings attempt to mimick life’s primitive RNAs. At most 25 22-nucleotide-long RNA rings code once for each biotic amino acid, a start and a stop codon and form a stem-loop hairpin, resembling consensus tRNAs. We calculated, for each RNA ring’s 22 potential splicing positions, similarities of predicted secondary structures with tRNA vs. rRNA secondary structures. Assuming rRNAs partly derived from tRNA accretions, we predict positive associations between relative secondary structure similarities with rRNAs over tRNAs and genetic code integration orders of RNA ring anticodon cognate amino acids. Analyses consider for each secondary structure all nucleotide triplets as potential anticodon. Anticodons for ancient, chemically inert cognate amino acids are most frequent in the 25 RNA rings. For RNA rings with primordial cognate amino acids according to tRNA-homology-derived anticodons, tRNA-homology and coding sequences coincide, these are separate for predicted cognate amino acids that presumably integrated late the genetic code. RNA ring secondary structure similarity with rRNA over tRNA secondary structures associates best with genetic code integration orders of anticodon cognate amino acids when assuming split anticodons (one and two nucleotides at the spliced RNA ring 5′ and 3′ extremities, respectively), and at predicted anticodon location in the spliced RNA ring’s midst. Results confirm RNA ring homologies with tRNAs and CDs, ancestral status of tRNA half genes split at anticodons, the tRNA-rRNA axis of RNA evolution, and that single theoretical minimal RNA rings potentially produce near-complete proto-tRNA sets. Hence genetic code pre-existence determines 25 short circular gene- and tRNA-like RNAs. Accounting for each potential splicing position, each RNA ring potentially translates most amino acids, realistically mimicks evolution of the tRNA-rRNA translation machinery. These RNA rings ‘of creation’ remind the uroboros’ (snake biting its tail) symbolism for creative regeneration.

Investigating Macrophages Plasticity Following Tumour–Immune Interactions During Oncolytic Therapies Abstract Over the last few years, oncolytic virus therapy has been recognised as a promising approach in cancer treatment, due to the potential of these viruses to induce systemic anti-tumour immunity and selectively killing tumour cells. However, the effectiveness of these viruses depends significantly on their interactions with the host immune responses, both innate (e.g., macrophages, which accumulate in high numbers inside solid tumours) and adaptive (e.g., \(\hbox {CD8}^{+}\) T cells). In this article, we consider a mathematical approach to investigate the possible outcomes of the complex interactions between two extreme types of macrophages (M1 and M2 cells), effector \(\hbox {CD8}^{+}\) T cells and an oncolytic Vesicular Stomatitis Virus (VSV), on the growth/elimination of B16F10 melanoma. We discuss, in terms of VSV, \(\hbox {CD8}^{+}\) and macrophages levels, two different types of immune responses which could ensure tumour control and eventual elimination. We show that both innate and adaptive anti-tumour immune responses, as well as the oncolytic virus, could be very important in delaying tumour relapse and eventually eliminating the tumour. Overall this study supports the use mathematical modelling to increase our understanding of the complex immune interaction following oncolytic virotherapies. However, the complexity of the model combined with a lack of sufficient data for model parametrisation has an impact on the possibility of making quantitative predictions.

Genotype Components as Predictors of Phenotype in Model Gene Regulatory Networks Abstract Models of gene regulatory networks (GRN) have proven useful for understanding many aspects of the highly complex behavior of biological control networks. Randomly generated non-Boolean networks were used in experimental simulations to generate data on dynamic phenotypes as a function of several genotypic parameters. We found that predictive relationships between some phenotypes and quantitative genotypic parameters such as number of network genes, interaction density, and initial condition could be derived depending on the strength of the topological (positional) genotype on specific phenotypes. We quantitated the strength of the topological genotype effect (TGE) on a number of phenotypes in multi-gene networks. For phenotypes with a low influence of topological genotype, derived and empirical relationships using quantitative genotype parameters were accurate in phenotypic outcomes. We found a number of dynamic network properties, including oscillation behaviors, that were largely dependent on genotype topology, and for which no such general quantitative relationships were determinable. It remains to be determined if these results are applicable to biological gene regulatory networks.

Optimality Models and the Propensity Interpretation of Fitness Abstract The propensity account of fitness intends to solve the classical tautologicity issue by identifying fitness with a disposition, the ability to survive and reproduce. As proponents recognized early on, this account requires operational independence from actual reproductive success to avoid circularity and vacuousness charges. They suggested that operational independence is achieved by measuring fitness values through optimality models. Our goal in this article is to develop this suggestion. We show that one plausible procedure by which these independent operationalizations could be thought to take place, and which is in accordance with what is said in the optimality literature, is unsound. We provide two independent lines of reasoning to show this. We then provide a sketch of a more adequate account of the role of optimality models in evolutionary contexts and draw some consequences.

Synapomorphies Behind Shared Derived Characters: Examples from the Great Apes’ Genomic Data Abstract Phylogenetic systematics (e.g., cladistics) is one of the most important analytical frameworks of modern Biology. It seems to be common knowledge that within phylogenetics, ‘groups’ must be defined based solely on the synapomorphies or on the “derived” characters that unite two or more taxa in a clade or monophyletic group. Thus, the idea of synapomorphy seems to be of fundamental influence and importance. Here I will show that the most common and straightforward understanding of synapomorphy as a shared derived character is not sufficient and eventually must be rejected in favor of Nelson’s relational interpretation of such term. Arguing for this point and using three examples from previously published Apes’ genomic matrices, I explicitly demonstrate that the relationship (Pongo (Gorilla (Homo, Pan))) with Hylobatidae as a sister taxon, may be successfully recovered by three-taxon statement analysis (3TA) and three-taxon statement average consensus analysis (3TS-ACA) even if all of the evident standard shared derived molecular characters of the relationship (Pongo (Gorilla (Homo, Pan))) with Hylobatidae as a sister taxon, have been excluded from the molecular alignments. Neither conventional Maximum Parsimony nor Maximum Likelihood or Bayesian Inference can do this in such situation. Thus, our results show that the relationship (Pongo (Gorilla (Homo, Pan))) with Hylobatidae as a sister taxon has appeared, in some way, behind standard shared derived characters: the last ones could be excluded, but the relationship remains the same.

Expansion Speed as a Generic Measure of Spread for Alien Species Abstract The ecological impact of alien species is a function of the area colonised. Impact assessments of alien species are thus incomplete unless they take the spatial component of invasion processes into account. This paper describes a measure, termed expansion speed, that quantifies the speed with which a species increases its spatial presence in an assessment area. It is based on the area of occupancy (AOO) and can be estimated from grid occupancies. Expansion speed is defined as the yearly increase in the radius of a coherent circle having the same area as the AOO, irrespective of whether the increase is due to natural dispersal or anthropogenic transport. Two methods for estimating expansion speed are presented: one that requires several years of spatio-temporal observation data and explicitly takes detection rates into account; and one that can be used under a situation with sparse data. Using simulations and real-world data from natural history collections, it is shown that the method provides a good fit to observational datasets. Expansion speed has several valuable properties. Being based on AOO, it is an intuitive measure; as it only requires occupancy data, it is comparatively easy to estimate; and because it is a quantitative and generic measure, it increases the testability and comparability of impact assessments of alien species.

The Cultural Evolution of Human Nature Abstract Recent years have seen the growing promise of cultural evolutionary theory as a new approach to bringing human behaviour fully within the broader evolutionary synthesis. This review of two recent seminal works on this topic argues that cultural evolution now holds the potential to bring together fields as disparate as neuroscience and social anthropology within a unified explanatory and ontological framework.

In Search of the Origins of Consciousness Abstract The Evolution of the Sensitive Soul is a landmark attempt to make progress on the problem of animal consciousness. Ginsburg and Jablonka propose a general cognitive marker of the presence of consciousness: Unlimited Associative Learning. They use this marker to defend a generous view about the distribution of consciousness in the natural world, on which a capacity for conscious experience is common to all vertebrates, many arthropods and some cephalopod molluscs. They use this inferred distribution to defend a view about the evolution of consciousness, on which it has evolved at least three times, first evolved at around the time of the Cambrian explosion (just over 500 million years ago), and was in fact the driving force behind that explosion. In this essay review, I reflect critically on the book’s central idea: the proposal that Unlimited Associative Learning provides a general marker of consciousness.

Individuation and the Organization in Complex Living Ecosystem: Recursive Integration and Self-assertion by Holon-Lymphocytes Abstract Individuation and organization in complex living multi-level ecosystem occurs as dynamical processes from early ontogeny. The notion of living “holon” displaying dynamic self-assertion and integration is used here to explain the ecosystems dynamic processes. The update of the living holon state according to the continuous change of the dynamic system allows for its viability. This is interpreted as adaptation, selection and organization by the human that observes the system a posteriori from its level. Our model concerns the complex dynamics of the adaptive immune system, integrating holon-lymphocytes that collectively preserve the identity and integrity of the organism. Each lymphocyte individualizes as a dynamic holon-lymphocyte, with somatic gene individuation leading to an individual, singular antigen immunoreceptor type, promoting the self-assertion. In turn, the “Immunoception” allows for perception of the environmental antigenic context, thus integration of the holon in its environment. The self-assertion/integration of holon-lymphocyte starts from fetal stages and is influenced by mother Lamarckian acquired historicity transmissions, a requisite for the integrity of the holobiont-organism. We propose a dynamic model of the perception by holon-lymphocyte, and at the supra-clonal level of the immune system functions that sustain the identity and integrity of the holon-holobiont organism.

The Objectivity of Organizational Functions Abstract We critique the organizational account of biological functions by showing how its basis in the closure of constraints fails to be objective. While the account treats constraints as objective features of physical systems, the number and relationship of potential constraints are subject to potentially arbitrary redescription by investigators. For example, we show that self-maintaining systems such as candle flames can realize closure on a more thorough analysis of the case, contradicting the claim that these “simple” systems lack functional organization. This also raises problems for Moreno and Mossio’s associated theory of biological autonomy, which asserts that living beings are distinguished by their possession of a closed system of constraints that channel and regulate their metabolic processes.