The evolution of information storage and heredity

Many important transitions in evolution are associated with novel ways of storing and transmitting information. The storage of information in DNA sequence, and its transmission through DNA replication, is a fundamental hereditary system in all extant organisms, but it is not the only way of storing and transmitting information, and has itself replaced, and evolved from, other systems. A system that transmits information can have limited heredity or indefinite heredity. With limited heredity, the number of different possible types is commensurate with, or below, that of the individuals. With indefinite heredity, the number of possible types greatly exceeds the number of individuals in any realistic system. Recent findings suggest that the emergence and subsequent evolution of very different hereditary systems, from autocatalytic chemical cycles to natural language, accompanied the major evolutionary transitions in the history of life.     

Historical progress and the future of human cell culture research.

Progress in human cell culture research is discussed based primarily on our hematopoietic cell culture studies. The article includes a historical background of Burkitt lymphoma cell lines, discovery of EBV, normal B-lymphoblastoid cell lines with EBV, a variety of leukemia, lymphoma, and myeloma cell lines, clinical and theoretical contributions made by studies of T-cell leukemia cell lines, the discovery and clinical relevance of HTLV, HIV and HBLV, early attempts at adoptive immunotherapy of patients with cancer, and the future of human cell culture research. Despite the fact that current cell culture methods permit maintenance of only limited cell types of both normal and malignant origins, biotechnological advances such as hybridoma and recombinant DNA technologies should continue to provide unlimited research opportunities in all fields.     

From survivors to replicators: evolution by natural selection revisited

For evolution by natural selection to occur it is classically admitted that the three ingredients of variation, difference in fitness and heredity are necessary and sufficient. In this paper, I show using simple individual-based models, that evolution by natural selection can occur in populations of entities in which neither heredity nor reproduction are present. Furthermore, I demonstrate by complexifying these models that both reproduction and heredity are predictable Darwinian products (i.e. complex adaptations) of populations initially lacking these two properties but in which new variation is introduced via mutations. Later on, I show that replicators are not necessary for evolution by natural selection, but rather the ultimate product of such processes of adaptation. Finally, I assess the value of these models in three relevant domains for Darwinian evolution.     

Eco-evolutionary dynamics,coding structure and the information threshold

Background  

The amount of information that can be maintained in an evolutionary system of replicators is limited by genome length, the number of errors during replication (mutation rate) and various external factors that influence the selection pressure. To date, this phenomenon, known as the information threshold, has been studied (both genotypically and phenotypically) in a constant environment and with respect to maintenance (as opposed to accumulation) of information. Here we take a broader perspective on this problem by studying the accumulation of information in an ecosystem, given an evolvable coding structure. Moreover, our setup allows for individual based as well as ecosystem based solutions. That is, all functions can be performed by individual replicators, or complementing functions can be performed by different replicators. In this setup, where both the ecosystem and the individual genomes can evolve their structure, we study how populations cope with high mutation rates and accordingly how the information threshold might be alleviated.     

The evolution of enzyme specificity in the metabolic replicator model of prebiotic evolution

The chemical machinery of life must have been catalytic from the outset. Models of the chemical origins have attempted to explain the ecological mechanisms maintaining a minimum necessary diversity of prebiotic replicator enzymes, but little attention has been paid so far to the evolutionary initiation of that diversity. We propose a possible first step in this direction: based on our previous model of a surface-bound metabolic replicator system we try to explain how the adaptive specialization of enzymatic replicator populations might have led to more diverse and more efficient communities of cooperating replicators with two different enzyme activities. The key assumptions of the model are that mutations in the replicator population can lead towards a) both of the two different enzyme specificities in separate replicators: efficient "specialists" or b) a "generalist" replicator type with both enzyme specificities working at less efficiency, or c) a fast-replicating, non-enzymatic "parasite". We show that under realistic trade-off constraints on the phenotypic effects of these mutations the evolved replicator community will be usually composed of both types of specialists and of a limited abundance of parasites, provided that the replicators can slowly migrate on the mineral surface. It is only at very weak trade-offs that generalists take over in a phase-transition-like manner. The parasites do not seriously harm the system but can freely mutate, therefore they can be considered as pre-adaptations to later, useful functions that the metabolic system can adopt to increase its own fitness.     

Segmentation of Image Data from Complex Organotypic 3D Models of Cancer Tissues with Markov Random Fields

Organotypic, three dimensional (3D) cell culture models of epithelial tumour types such as prostate cancer recapitulate key aspects of the architecture and histology of solid cancers. Morphometric analysis of multicellular 3D organoids is particularly important when additional components such as the extracellular matrix and tumour microenvironment are included in the model. The complexity of such models has so far limited their successful implementation. There is a great need for automatic, accurate and robust image segmentation tools to facilitate the analysis of such biologically relevant 3D cell culture models. We present a segmentation method based on Markov random fields (MRFs) and illustrate our method using 3D stack image data from an organotypic 3D model of prostate cancer cells co-cultured with cancer-associated fibroblasts (CAFs). The 3D segmentation output suggests that these cell types are in physical contact with each other within the model, which has important implications for tumour biology. Segmentation performance is quantified using ground truth labels and we show how each step of our method increases segmentation accuracy. We provide the ground truth labels along with the image data and code. Using independent image data we show that our segmentation method is also more generally applicable to other types of cellular microscopy and not only limited to fluorescence microscopy.     

Carbofuran-degrading bacteria from previously treated field soils

Laboratory incubation studies were made on soils collected from five field sites with different histories of treatment with carbofuran. All soils treated earlier with carbofuran degraded the compound more rapidly than untreated samples of the same soils. Reduced rates of degradation in the presence of chloramphenicol imply that soil bacteria are primarily responsible for the breakdown of carbofuran in these soils. Sixty-eight bacteria, capable of degrading carbofuran as the sole source of carbon and nitrogen, were isolated from liquid cultures of treated soils. The concentration of carbofuran in the liquid medium used for isolation and subsequent culture of carbofuran-degrading isolates appeared to affect the stability of their ability to degrade. Similar types of carbofuran-degrading bacteria were isolated from different soils and several different types were isolated from one soil. All carbofuran-degrading isolates were Gram-negative, aerobic rods which hydrolysed the insecticide to carbofuran phenol. They were separated into four groups on the basis of a limited number of phenotypic characters. There was a good correlation between the phenotype of carbofuran-degrading isolates and the stability of their ability to degrade. Fourteen isolates were placed in phenotypic group I and 13 of these did not degrade carbofuran after one subculture in liquid medium. Phenotypic groups II, III and IV consisted of 54 isolates in total (3, 46 and 5 isolates respectively) and 52 of these retained their ability to degrade carbofuran when subcultured.     

The replicon revisited: an old model learns new tricks in metazoan chromosomes

The origins of DNA replication were proposed in the replicon model to be specified genetically by replicator elements that coordinate the initiation of DNA synthesis with gene expression and cell growth. Recent studies have identified DNA sequences in mammalian cells that fulfil the genetic criteria for replicators and are beginning to uncover the sequence requirements for the initiation of DNA replication. Mammalian replicators are com- posed of non-redundant modules that cooperate to direct initiation to specific chromosomal sites. Conversely, replicators do not show strong sequence similarity, and their ability to initiate replication depends on the chromosomal context and epigenetic factors, as well as their primary sequence. Here, we review the properties of metazoan replicators, and discuss the genetic and epigenetic factors that determine where and when DNA replication is initiated.     

An error limit for the evolution of language

On the evolutionary trajectory that led to human language there must have been a transition from a fairly limited to an essentially unlimited communication system. The structure of modern human languages reveals at least two steps that are required for such a transition: in all languages (i) a small number of phonemes are used to generate a large number of words; and (ii) a large number of words are used to a produce an unlimited number of sentences. The first (and simpler) step is the topic of the current paper. We study the evolution of communication in the presence of errors and show that this limits the number of objects (or concepts) that can be described by a simple communication system. The evolutionary optimum is achieved by using only a small number of signals to describe a few valuable concepts. Adding more signals does not increase the fitness of a language. This represents an error limit for the evolution of communication. We show that this error limit can be overcome by combining signals (phonemes) into words. The transition from an analogue to a digital system was a necessary step toward the evolution of human language.     

Malaria control: present situation and need for historical research

A rapid review is made of the history of malaria control, calling attention to differences between the evolution of the technical concepts, the formulated strategies and their implementation. Particular emphasis is placed on the discussion of the present situation of the world malaria problem and the difficulties faced by many endemic countries in adopting a malaria control strategy, based on primary health care, while their services are vertically organized for the performance of routines, which are irrelevant for disease control. The present malaria control strategy recognizes local variability, but it is possible to identify a limited number of types of situations, likely to respond to similar approaches. The definition not only of the control approaches but also of their conditions of applicability will become more precise as experiences are accumulated and adequately documented from different types of epidemiological situations. It is postulated that historical research on the malaria control and public health approaches, with proper attention being given to their socioeconomic and political context, in the countries which succeeded in controlling endemic malaria, will make an important contribution to such a definition.     

Less can be more: RNA-adapters may enhance coding capacity of replicators

It is still not clear how prebiotic replicators evolved towards the complexity found in present day organisms. Within the most realistic scenario for prebiotic evolution, known as the RNA world hypothesis, such complexity has arisen from replicators consisting solely of RNA. Within contemporary life, remarkably many RNAs are involved in modifying other RNAs. In hindsight, such RNA-RNA modification might have helped in alleviating the limits of complexity posed by the information threshold for RNA-only replicators. Here we study the possible role of such self-modification in early evolution, by modeling the evolution of protocells as evolving replicators, which have the opportunity to incorporate these mechanisms as a molecular tool. Evolution is studied towards a set of 25 arbitrary 'functional' structures, while avoiding all other (misfolded) structures, which are considered to be toxic and increase the death-rate of a protocell. The modeled protocells contain a genotype of different RNA-sequences while their phenotype is the ensemble of secondary structures they can potentially produce from these RNA-sequences. One of the secondary structures explicitly codes for a simple sequence-modification tool. This 'RNA-adapter' can block certain positions on other RNA-sequences through antisense base-pairing. The altered sequence can produce an alternative secondary structure, which may or may not be functional. We show that the modifying potential of interacting RNA-sequences enables these protocells to evolve high fitness under high mutation rates. Moreover, our model shows that because of toxicity of misfolded molecules, redundant coding impedes the evolution of self-modification machinery, in effect restraining the evolvability of coding structures. Hence, high mutation rates can actually promote the evolution of complex coding structures by reducing redundant coding. Protocells can successfully use RNA-adapters to modify their genotype-phenotype mapping in order to enhance the coding capacity of their genome and fit more information on smaller sized genomes.     

Selection without replicators: the origin of genes, and the replicator/interactor distinction in etiobiology

Genes are thought to have evolved from long-lived and multiply-interactive molecules in the early stages of the origins of life. However, at that stage there were no replicators, and the distinction between interactors and replicators did not yet apply. Nevertheless, the process of evolution that proceeded from initial autocatalytic hypercycles to full organisms was a Darwinian process of selection of favourable variants. We distinguish therefore between Neo-Darwinian evolution and the related Weismannian and Central Dogma divisions, on the one hand, and the more generic category of Darwinian evolution on the other. We argue that Hull’s and Dawkins’ replicator/interactor distinction of entities is a sufficient, but not necessary, condition for Darwinian evolution to take place. We conceive the origin of genes as a separation between different types of molecules in a thermodynamic state space, and employ a notion of reproducers.     

Effect of host availability on reproduction and survival of the parasitoid wasp Trichogramma minutum

Abstract.

• 1 We tested the hypothesis that females of the egg parasitoid, Trichogramma minutum Riley (Hymenoptera: Trichogrammatidae), could adjust their fecundity schedule according to host availability and that there was a negative correlation between reproduction and survival in these wasps.
• 2 Newly-emerged females were provided with an unlimited or limited number of hosts in the first trial and with either unlimited, limited or zero hosts in the second trial.
• 3 When hosts were unlimited, wasps had the highest rate of reproduction in the first day, which decreased dramatically thereafter. When hosts were limited, wasps from the two trials differed in their response. In Trial I, females with limited hosts had lower first-day fecundity than, and the same subsequent-day fecundity as, those with unlimited hosts. However, in Trial II, females with limited host had a lower first-day but a higher subsequent-day fecundity than those with unlimited hosts. This indicates variation in Trichogramma's ability to shift its fecundity schedule in response to host availability.
• 4 There was a positive (rather than a negative) correlation between reproduction and survival. Wasps that oviposited (in host-unlimited treatment) had greater longevity than those that could not (in host-unavailable treatment).
• 5 The sex ratio of the progeny produced by wasps in both host-unlimited and limited treatments shifted gradually from a female to a male bias as the wasps aged.
• 6 We consider the ability of parasitoids to adjust their fecundity schedule as an adaptation to changing host resources and discuss our findings with regard to theories of life history evolution.

     

Limited versus unlimited membership in microbial communities: evaluation and experimental tests of some paradigms

Recent developments in community ecology have allowed for the synthesis of community models based on principles of limited and unlimited membership. In this discussion, these developments are used as a framework for evaluating the validity of three paradigms that have constrained research on aquatic microbial communities. Because microbes are considered to possess global distributions, species availability is not generally considered to be an important factor determining microbial community composition in most habitats. Requirements for the global distribution of a species are not the same as those for unlimited availability. Rates of propagule transport to isolated and newly formed aquatic systems ( 4 years old) are low enough to have a strong effect on microbial community composition. Natural aquatic systems may require several years to accumulate a full complement of species adapted to environmental conditions at a particular time. Except under extreme circumstances, environmental conditions are not considered to constrain membership in aquatic microbial communities. Most evidence for this contention is based on an inability to detect simple relationships between species distributions and levels of individual environmental parameters. Environmental measurements are often made at a spatial scale much greater than that of the local environment of microbes. Biotic interactions, such as competition, are generally considered to be the predominant force structuring aquatic microbial communities. Although there is an extensive laboratory database to suggest the importance of different types of species interactions, there have been few field studies to confirm this. A general research protocol is described to test predictions derived from current theory of microbial community organization. A mesocosm approach is advocated in order to incorporate crucial aspects of environmental realism into experimental designs while maintaining some of the control found in the laboratory.     

Rethinking heredity, again

The refutation of 'soft' inheritance and establishment of Mendelian genetics as the exclusive model of heredity is widely portrayed as an iconic success story of scientific progress. Yet, we are witnessing a re-emergence of debate on the role of soft inheritance in heredity and evolution. I argue that this reversal reflects not only the weight of new evidence but also an important conceptual change. I show that the concept of soft inheritance rejected by 20th-century genetics differs fundamentally from the current concept of 'nongenetic inheritance'. Moreover, whereas it has long been assumed that heredity is mediated by a single, universal mechanism, a pluralistic model of heredity is now emerging, based on a recognition of multiple, parallel mechanisms of inheritance.     

Self-renewing endodermal progenitor lines generated from human pluripotent stem cells

The use of human pluripotent stem cells for laboratory studies and cell-based therapies is hampered by their tumor-forming potential and limited ability to generate pure populations of differentiated cell types in vitro. To address these issues, we established endodermal progenitor (EP) cell lines from human embryonic and induced pluripotent stem cells. Optimized growth conditions were established that allow near unlimited (>10(16)) EP cell self-renewal in which they display a morphology and gene expression pattern characteristic of definitive endoderm. Upon manipulation of their culture conditions in vitro or transplantation into mice, clonally derived EP cells differentiate into numerous endodermal lineages, including monohormonal glucose-responsive pancreatic β-cells, hepatocytes, and intestinal epithelia. Importantly, EP cells are nontumorigenic in vivo. Thus, EP cells represent a powerful tool to study endoderm specification and offer a potentially safe source of endodermal-derived tissues for transplantation therapies.     

A mathematical model of proliferation and aging of cells in culture

A mathematical model is presented which describes the proliferative senescence of cells in culture. The model is based on the DNA damage hypothesis of cellular aging and is able to account for both the limited and unlimited in vitro proliferative potential of normal and transformed cells. It is predicted that the destiny of a cell population is determined by two counteracting factors: the proliferation rate of the dividable cells and the gene damage accumulation rate. The formation of an immortal cell line requires high rate of proliferation and/or low rate of gene damage accumulation. The related computer simulations on a number of proliferative properties of cell culture produces results in agreement, in the general properties, with experimental observations.     

Multilevel Selection in Models of Prebiotic Evolution: Compartments and Spatial Self-organization

In this paper we explore the impact of new levels ofselection in models of early evolution.We contrast two types of higher levels of selection. On the one hand we look at spatially explicitmodels of replicators in which, by a process of self-organization, new levels of selection ariseas large scale spatial patterns with a dynamics of their own. Alternatively externally imposedlevels of selection above the basic replicators are created by enclosing the replicators in vesicles.In this paper we first review some results on the impact of emerging higher levels of selection onthe evolutionary persistence of interacting co-evolvingreplicator systems. Moreover, we presenta vesicle model, which can potentially integrate emerging and imposed levels of selection. We use the models to examinethe classical problem information integration in early evolution.Supplementary material to this paper is available in electronic form at http://dx.doi.org/10.1023/A:1025754907141     

Protein-mediated Selective Enclosure of Early Replicators Inside of Membranous Vesicles: First Step Towards Cell Membranes

Containment in cell membranes is essential for all contemporary life, and apparently even the earliest life forms had to be somehow contained. It has been postulated that random enclosure of replicating molecules inside of spontaneously assembled vesicles would have formed the initial cellular ancestors. However, completely random re-formation or division of such primitive vesicles would have abolished the heritability of their contents, nullifying any selective advantage to them. We propose that the containment of the early replicators in membranous vesicles was adopted only after the invention of genetically encoded proteins, and that selective enclosure of target molecules was mediated by specific proteins. A similar containment process is still utilised by various RNA- and retroviruses to isolate their replication complexes from the host’s intracellular environment. Such selective encapsulation would have protected the replicators against competitor and parasitic sequences, and provided a strong positive selection within the replicator communities.