Are amyloid fibrils molecular spandrels?

Amyloid-β, the protein implicated in Alzheimer’s disease, along with a number of other proteins, has been shown to form amyloid fibrils. Fibril forming proteins share no common primary structure and have little known function. Furthermore, all proteins have the ability to form amyloid fibrils under certain conditions as the fibrillar structure lies at the global free energy minimum of proteins. This raises the question of the mechanism of the evolution of the amyloid fibril structure. Experimental evidence supports the hypothesis that the fibril structure is a by-product of the forces of protein folding and lies outside the bounds of evolutionary pressures.     

Does constructive neutral evolution play an important role in the origin of cellular complexity?

Recently, constructive neutral evolution has been touted as an important concept for the understanding of the emergence of cellular complexity. It has been invoked to help explain the development and retention of, amongst others, RNA splicing, RNA editing and ribosomal and mitochondrial respiratory chain complexity. The theory originated as a welcome explanation of isolated small scale cellular idiosyncrasies and as a reaction to 'overselectionism'. Here I contend, that in its extended form, it has major conceptual problems, can not explain observed patterns of complex processes, is too easily dismissive of alternative selectionist models, underestimates the creative force of complexity as such, and--if seen as a major evolutionary mechanism for all organisms--could stifle further thought regarding the evolution of highly complex biological processes.     

Are aberrant phase transitions a driver of cellular aging?

Why do cells age? Recent advances show that the cytoplasm is organized into many membrane‐less compartments via a process known as phase separation, which ensures spatiotemporal control over diffusion‐limited biochemical reactions. Although phase separation is a powerful mechanism to organize biochemical reactions, it comes with the trade‐off that it is extremely sensitive to changes in physical‐chemical parameters, such as protein concentration, pH, or cellular energy levels. Here, we highlight recent findings showing that age‐related neurodegenerative diseases are linked to aberrant phase transitions in neurons. We discuss how these aberrant phase transitions could be tied to a failure to maintain physiological physical‐chemical conditions. We generalize this idea to suggest that the process of cellular aging involves a progressive loss of the organization of phase‐separated compartments in the cytoplasm.

     

On the nature and origin of cellular complexity: The combinatorial–eukaryogenetic scenario

The ideas on the nature and origin of the cell nucleus published by K.S. Merezhkowsky in his book The Theory of Two Plasms as the Basis of Symbiogenesis, a New Study on the Origins of Organisms (1909) are still relevant. In this book, Merezhkowsky (1909, p. 86) wrote, “Part of my theory related to the nucleus, its nature and origin will be the subject of a separate paper, which will present facts serving as the basis for the ideas, which are here only touched upon briefly.” For various reasons, he was not able to publish the paper intended. Therefore, I here attempt to interpret Merezhkowsky’s original concepts on the nature and origin of the cell nucleus in a modern context.     

Do motifs reflect evolved function?--No convergent evolution of genetic regulatory network subgraph topologies

Methods that analyse the topological structure of networks have recently become quite popular. Whether motifs (subgraph patterns that occur more often than in randomized networks) have specific functions as elementary computational circuits has been cause for debate. As the question is difficult to resolve with currently available biological data, we approach the issue using networks that abstractly model natural genetic regulatory networks (GRNs) which are evolved to show dynamical behaviors. Specifically one group of networks was evolved to be capable of exhibiting two different behaviors ("differentiation") in contrast to a group with a single target behavior. In both groups we find motif distribution differences within the groups to be larger than differences between them, indicating that evolutionary niches (target functions) do not necessarily mold network structure uniquely. These results show that variability operators can have a stronger influence on network topologies than selection pressures, especially when many topologies can create similar dynamics. Moreover, analysis of motif functional relevance by lesioning did not suggest that motifs were of greater importance to the functioning of the network than arbitrary subgraph patterns. Only when drastically restricting network size, so that one motif corresponds to a whole functionally evolved network, was preference for particular connection patterns found. This suggests that in non-restricted, bigger networks, entanglement with the rest of the network hinders topological subgraph analysis.     

A method to the madness of N-glycan complexity?

Cell-surface glycoprotein receptors have varying numbers of N-glycan sites. In this issue of Cell, Lau et al. (2007) report that increasing intracellular UDP-GlcNAc leads to increased branching of N-glycans, increased receptor association with cell-surface galectin-3, and enhanced signaling. They also show that the kinetics of this response differ between growth-promoting receptors, which have 8-16 N-glycans, and those that induce growth arrest, which have very few N-glycans, suggesting that hexosamine flux may regulate the transition from growth to arrest.     

Metabolic enzymes that bind RNA: yet another level of cellular regulatory network?

Several enzymes that were originally characterized to have one defined function in intermediatory metabolism are now shown to participate in a number of other cellular processes. Multifunctional proteins may be crucial for building of the highly complex networks that maintain the function and structure in the eukaryotic cell possessing a relatively low number of protein-encoding genes. One facet of this phenomenon, on which I will focus in this review, is the interaction of metabolic enzymes with RNA. The list of such enzymes known to be associated with RNA is constantly expanding, but the most intriguing question remains unanswered: are the metabolic enzyme-RNA interactions relevant in the regulation of cell metabolism? It has been proposed that metabolic RNA-binding enzymes participate in general regulatory circuits linking a metabolic function to a regulatory mechanism, similar to the situation of the metabolic enzyme aconitase, which also functions as iron-responsive RNA-binding regulatory element. However, some authors have cautioned that some of such enzymes may merely represent "molecular fossils" of the transition from an RNA to a protein world and that the RNA-binding properties may not have a functional significance. Here I will describe enzymes that have been shown to interact with RNA (in several cases a newly discovered RNA-binding protein has been identified as a well-known metabolic enzyme) and particularly point out those whose ability to interact with RNA seems to have a proven physiological significance. I will also try to depict the molecular switch between an enzyme's metabolic and regulatory functions in cases where such a mechanism has been elucidated. For most of these enzymes relations between their enzymatic functions and RNA metabolism are unclear or seem not to exist. All these enzymes are ancient, as judged by their wide distribution, and participate in fundamental biochemical pathways.     

Can landscape ecology untangle the complexity of antibiotic resistance?

Bacterial resistance to antibiotics continues to pose a serious threat to human and animal health. Given the considerable spatial and temporal heterogeneity in the distribution of resistance and the factors that affect its evolution, dissemination and persistence, we argue that antibiotic resistance must be viewed as an ecological problem. A fundamental difficulty in assessing the causal relationship between antibiotic use and resistance is the confounding influence of geography: the co-localization of resistant bacterial species with antibiotic use does not necessarily imply causation and could represent the presence of environmental conditions and factors that have independently contributed to the occurrence of resistance. Here, we show how landscape ecology, which links the biotic and abiotic factors of an ecosystem, might help to untangle the complexity of antibiotic resistance and improve the interpretation of ecological studies.     

Do protein motifs read the histone code?

The existence of different patterns of chemical modifications (acetylation, methylation, phosphorylation, ubiquitination and ADP-ribosylation) of the histone tails led, some years ago, to the histone code hypothesis. According to this hypothesis, these modifications would provide binding sites for proteins that can change the chromatin state to either active or repressed. Interestingly, some protein domains present in histone-modifying enzymes are known to interact with these covalent marks in the histone tails. This was first shown for the bromodomain, which was found to interact selectively with acetylated lysines at the histone tails. More recently, it has been described that the chromodomain can be targeted to methylation marks in histone N-terminal domains. Finally, the interaction between the SANT domain and histones is also well documented. Overall, experimental evidence suggests that these domains could be involved in the recruitment of histone-modifying enzymes to discrete chromosomal locations, and/or in the regulation their enzymatic activity. Within this context, we review the distribution of bromodomains, chromodomains and SANT domains among chromatin-modifying enzymes and discuss how they can contribute to the translation of the histone code.     

Are macroinvertebrate communities influenced by seagrass structural complexity?

A study was undertaken within a sub-tidal Zostera marina seagrass bed (Devon, U.K.), with the aim of elucidating the relationship between seagrass structural complexity and the size and composition of the associated macroinvertebrate community. Samples of macroinvertebrates were recovered from three designated areas of shoot density. Various physical characteristics were measured for individual plants, and an a priori complexity index was determined relevant to the associated target organisms. Resulting data were analysed using linear regression and multivariate techniques. Significant relationships were found between shoot density and number of leaves/shoot, leaf length, stem length and algal epiphyte biomass. Neither the number of species nor abundance of macroinvertebrates was significantly related with the derived complexity index. Multivariate analysis indicated that macroinvertebrate communities from the three areas of shoot density were significantly different, the pattern of macroinvertebrate community composition being best explained by sea-grass biomass. Linear regression of seagrass biomass with macroinvertebrate number of species and abundance revealed significant positive relationships. Regression also indicated that there was no significant increase in complexity with increasing seagrass biomass. The results suggest that within a seagrass bed the size and composition of the associated macroinvertebrate community is not determined by the structural complexity of the plants, but by the amount of plant available. This finding indicates a simple species-area relationship, and arguably one brought about as a result of a sampling artefact. Thus, the current paradigm that structural complexity of seagrass is responsible for increased species diversity, can only be justifiably applied to comparisons between seagrass and other habitats, and not within a seagrass bed itself.     

Are islands the end of the colonization road?

Ecologists have, up to now, widely regarded colonization of islands from continents as a one-way journey, mainly because of widely accepted assertions that less diverse island communities are easier to invade. However, continents present large targets and island species should be capable of making the reverse journey, considering they are the direct descendants of successful colonists and provided that they have not lost their dispersal abilities. Recent mapping of geography onto molecular phylogenies has revealed several cases of 'reverse colonization' (from islands to continents). We suggest this phenomenon warrants closer attention in ecology and biogeography. Assessing its significance will contribute to understanding the role of dispersal and establishment in biogeographic distributions and the assembly of natural biotas.     

Are the carotid bodies of the guinea-pig functional?

We have previously observed that the guinea-pig appears to have a relatively poor ventilatory (V (E)) response to hypoxia, compared to other mammals. Therefore, in this study, we questioned the ability of the carotid bodies (primary peripheral chemoreceptors) in the guinea-pig to detect hypoxia. The ventilatory responses to poikilocapnic hypoxia (8% O(2)), poikilooxic hypercapnia (8% CO(2)), hyperoxia (100% O(2)) and cyanide (NaCN - 200 mug/kg, i.v.) were assessed before and after carotid body denervation (CBD) in anaesthetized guinea-pigs. Although CBD attenuated the V (E) responses to hypercapnia and cyanide, it had no effect on normoxic breathing or the V (E) responses to hypoxia or hyperoxia. In a separate group of guinea-pigs, nerve activity was recorded from single or few-fibre preparations of the carotid sinus nerve (CSN). Basal chemoreceptor activity could not be detected from any of the nerve preparations. NaCN and hypercapnia consistently provoked an increase in neural activity. In contrast, hypoxia never clearly increased activity in any of the single or few-fibre preparations isolated from the CSN. In conclusion, although the carotid bodies of the guinea-pig, like those of other mammals, are able to detect hypercapnia and histotoxic hypoxia and elicit a reflex increase in V (E), they are essentially hypoxia-insensitive. The latter may explain, at least in part, the relatively poor V (E) response to hypoxia shown by the guinea-pig.     

Are glycosyltransferases the evolutionary antecedents of the immunoglobulins?

The glycosyltransferases may be the evolutionary precursors of the immunoglobulins, although critical evidence for this hypothesis is not yet available. The transferases add sugars to non-glycosylated proteins, lipids, and organic molecules, as well as to oligosaccharides, glycoproteins, and glycolipids. The enzymes are specific, extremely polymorphic, occasionally inducible, and may be structurally related to one another. Circumstantial evidence links the transferases to both the MHC and T/t loci in the mouse. Finally, antibodies against purified transferases are difficult to produce and sometimes they react with immunoglobulins. The present hypothesis predicts that transferases should show some sequence homology with immunoglobulins, and that some MHC proteins will be glycosyltransferases.