Evolution and self-assembly of protocells

Cells define the minimal building blocks of life. How cellular life emerged and evolved implies to cross the boundary between living and nonliving matter. Here we explore this problem by presenting several relevant components of the whole picture involving chemistry, physics and natural selection. Available evidence suggests that the basic logic of life can be understood and eventually translated into synthetic forms of cellular life. A simple, physically sound model of information-free protocell replication suggests that the basic logic of how to couple metabolism and container can be more relevant than the specific set of parameters used, thus indicating that the emergence of cells might have been easier than we would expect.     

Systems biology and the origins of life? Part I. Are biochemical networks possible ancestors of living systems? Reproduction,identity and sensitivity to signals of biochemical networks

The set of these two theoretical papers offers an alternative to the hypothesis of a primordial RNA-world. The basic idea of these papers is to consider that the first prebiotic systems could have been networks of catalysed reactions encapsulated by a membrane. In order to test this hypothesis it was attempted to list the main obligatory features of living systems and see whether encapsulated biochemical networks could possibly display these features. The traits of living systems are the following: the ability they have to reproduce; the fact they possess an identity; the fact that biological events should be considered in the context of a history; the fact that living systems are able to evolve by selection of alterations of their structure and self-organization. The aim of these two papers is precisely to show that encapsulated biochemical networks can possess these properties and can be considered good candidates for the first prebiotic systems. In the present paper it is shown that if the proteinoids are not very specific catalysts and if some of the reactions of the network are autocatalytic whereas others are not, the resulting system does not reach a steady-state and tends to duplicate. In the same line, these biochemical networks possess an identity, viz. an information, defined from the probability of occurrence of these nodes. Moreover interaction of two ligands can increase, or decrease, this information. In the first case, the system is defined as emergent, in the second case it is considered integrated. Another property of living systems is that their behaviour is defined in the context of a time-arrow. For instance, they are able to sense whether the intensity of a signal is reached after an increase, or a decrease. This property can be mimicked by a simple physico-chemical system made up of the diffusion of a ligand followed by its chemical transformation catalysed by a proteinoid displaying inhibition by excess substrate. Under these conditions the system reacts differently depending on whether the same ligand concentration is reached after an increase or a decrease.     

Getting closer to a pre-vertebrate genome: the non-LTR retrotransposons of Branchiostoma floridae

Non-LTR retrotransposons are common in vertebrate genomes and although present in invertebrates they appear at a much lower frequency. The cephalochordate amphioxus is the closest living relative to vertebrates and has been considered a good model for comparative analyses of genome expansions during vertebrate evolution. With the aim to assess the involvement of transposable elements in these events, we have analysed the non-LTR retrotransposons of Branchiostoma floridae. In silico searches have allowed to reconstruct non-LTR elements of six different clades (CR1, I, L1, L2, NeSL and RTE) and assess their structural features. According to the estimated copy number of these elements they account for less than 1% of the haploid genome, which reminds of the low abundance also encountered in the urochordate Ciona intestinalis. Amphioxus (B. floridae) and Ciona share a pre-vertebrate-like organization for the non-LTR retrotransposons (<150 copies, < 1% of the genome) versus the complexity associated to higher vertebrates (Homo sapiens >1.3.10(6) copies, > 20% of the genome).     

Anti-inflammatory and immunosuppressive drugs and reproduction

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.     

Controlling chaos in ecology: From deterministic to individual-based models

The possibility of chaos control in biological systems has been stimulated by recent advances in the study of heart and brain tissue dynamics. More recently, some authors have conjectured that such a method might be applied to population dynamics and even play a nontrivial evolutionary role in ecology. In this paper we explore this idea by means of both mathematical and individual-based simulation models. Because of the intrinsic noise linked to individual behavior, controlling a noisy system becomes more difficult but, as shown here, it is a feasible task allowed to be experimentally tested.     

Mutagenic stress modulates the dynamics of CTG repeat instability associated with myotonic dystrophy type 1

The molecular basis of the myotonic dystrophy type 1 is the expansion of a CTG repeat at the DMPK locus. The expanded disease-associated repeats are unstable in both somatic and germ lines, with a high tendency towards expansion. The rate of expansion is directly related to the size of the pathogenic allele, increasing the size heterogeneity with age. It has also been suggested that additional factors, including as yet unidentified environmental factors, might affect the instability of the expanded CTG repeats to account for the observed CTG size dynamics over time. To investigate the effect of environmental factors in the CTG repeat instability, three lymphoblastoid cell lines were established from two myotonic dystrophy patients and one healthy individual, and parallel cultures were concurrently expanded in the presence or absence of the mutagenic chemical mitomycin C for a total of 12 population doublings. The new alleles arising along the passages were analysed by radioactive small pool PCR and sequencing gels. An expansion bias of the stepwise mutation was observed in a (CTG)₁₂₄ allele of a cell line harbouring two modal alleles of 28 and 124 CTG repeats. Interestingly, this expansion bias was clearly enhanced in the presence of mitomycin C. The effect of mitomycin C was also evident in the normal size alleles in two cell lines with alleles of 13/13 and 12/69 repeats, where treated cultures showed new longer alleles. In conclusion, our results indicate that mitomycin C modulates the dynamics of myotonic dystrophy-associated CTG repeats in LBCLs, enhancing the expansion bias of long-pathogenic repeats and promoting the expansion of normal length repeats.     

Coinfection and superinfection in RNA virus populations: a selection-mutation model

In this paper, we present a general selection-mutation model of evolution on a one-dimensional continuous fitness space. The formulation of our model includes both the classical diffusion approach to mutation process as well as an alternative approach based on an integral operator with a mutation kernel. We show that both approaches produce fundamentally equivalent results. To illustrate the suitability of our model, we focus its analytical study into its application to recent experimental studies of in vitro viral evolution. More specifically, these experiments were designed to test previous theoretical predictions regarding the effects of multiple infection dynamics (i.e., coinfection and superinfection) on the virulence of evolving viral populations. The results of these experiments, however, did not match with previous theory. By contrast, the model we present here helps to understand the underlying viral dynamics on these experiments and makes new testable predictions about the role of parameters such the time between successive infections and the growth rates of resident and invading populations.     

Adaptive walks in a gene network model of morphogenesis: insights into the Cambrian explosion

The emergence of complex patterns of organization close to the Cambrian boundary is known to have happened over a (geologically) short period of time. It involved the rapid diversification of body plans and stands as one of the major transitions in evolution. How it took place is a controversial issue. Here we explore this problem by considering a simple model of pattern formation in multicellular organisms. By modeling gene network-based morphogenesis and its evolution through adaptive walks, we explore the question of how combinatorial explosions might have been actually involved in the Cambrian event. Here we show that a small amount of genetic complexity including both gene regulation and cell-cell signaling allows one to generate an extraordinary repertoire of stable spatial patterns of gene expression compatible with observed anteroposterior patterns in early development of metazoans. The consequences for the understanding of the tempo and mode of the Cambrian event are outlined.