The Articulata hypothesis – or what is a segment?

The long held view that annelids and arthropods are closely related (Articulata) has been challenged recently by phylogenetic analyses using molecular data. The outcome of these studies is a clade of moulting animals (Ecdysozoa) comprising arthropods and some taxa of the nemathelminth worms. Monophyly of the Ecdysozoa has not yet been shown convincingly on morphological evidence, but is strongly supported by molecular data. The implication of the Ecdysozoa hypothesis is that the type of segmentation found in annelids and arthropods must be either convergent or an ancestral feature of protostomes or even bilaterians. The present review discusses aspects of segmentation in annelids and arthropods at the genetic, cellular, morphogenetic and morphological levels. Based on numerous similarities not shared with other bilaterian taxa it is suggested that segmentation of annelids and arthropods is homologous and apomorphic for a monophyletic Articulata. However, the challenge provided by the molecular analyses should stimulate research programmes gaining more data such as on additional genes, cleavage patterns, molecular developmental biology, and the comparison of nervous systems at the level of single neurons.     

What is behind the variation in mate quality dependent sex ratio adjustment? – A meta‐analysis

Theory predicts that parents adjust the sex ratio of their brood to the sexually selected traits of their mate because the reproductive success of sons may be more dependent on inherited paternal attractiveness than that of daughters. Empirical studies vary in terms of whether they support the theory, and this variation has often been regarded as evidence against sex ratio adjustment or has been ascribed to methodological differences. Applying phylogenetic meta‐analyses, we aimed to find biological explanations for the variation observed in songbirds. In particular, we tested the role extra‐pair paternity, because infidelity occurs in the majority of these species and may reduce the adaptive value of adjusting brood sex ratio to the phenotype of the social mate. However, we found that the variation in effect sizes was unrelated to the proportion of extra‐pair paternity. Thus future studies should consider that mate quality dependent sex ratio adjustment may be driven by direct (material) rather than indirect (genetic) benefits. We also tested if the effect sizes are influenced by whether the focal male trait is indeed under sexual selection as it is assumed by the sex allocation theory. We found that for male traits with proven role in sexual selection, effect sizes significantly differed from the null expectation of random production of sons and daughters. For male traits with only presumed sexual role in sexual selection, the deviation from the null expectation was less convincing, and the effect sizes were significantly smaller. This result indicates that studies that neglect the assumptions of the hypotheses concerned, may lead to the underestimation of the mean effect size and, eventually, false conclusions.     

Vitally important – does early innate immunity predict recruitment and adult innate immunity?

The immune system is one of the most important adaptations that has evolved to protect animals from a wide range of pathogens they encounter from early life onwards. During the early developmental period this is particularly true for the innate immunity, as other components of the immune system are, as yet, poorly developed. But innate immunity may not only be crucial for early life survival, but may also have long‐lasting effects, for example if early life immunity reflects the functioning of the immune system as a whole. For this reason, we investigated the importance of four constitutive innate immune parameters (natural antibodies, complement activity, concentrations of haptoglobin, and concentrations of nitric oxide) for recruitment in free‐living great tits. We compared nestling immunity of recruits with nestling immunity of their nonrecruited siblings. We also investigated within individual consistency of these innate immune parameters for those individuals that recruited, which may be taken as a measure of immune capacity. In accordance with previous studies, we found a clear effect of tarsus length and a trend for body mass on the likelihood to recruit. Nevertheless, we found no evidence that higher levels of constitutive innate immunity as a nestling facilitated local recruitment. Furthermore, individual innate immunity was not consistent across life stages, that is to say, nestling immune parameters did not determine, or respectively, reflect adult innate immune parameters. This plasticity in innate immune components may explain why we did not find long‐lasting survival benefits.     

Competition on productivity gradients – what do we expect?

Many experimental studies have quantified how the effects of competition vary with habitat productivity, with the results often interpreted in terms of the ideas of Grime and Tilman. Unfortunately, these ideas are not relevant to many experiments, and so we develop an appropriate resource competition model and use this to explore the effects of habitat productivity on the intensity of competition. Several mechanisms influencing the productivity–competition intensity relationship are identified, and these mechanisms explored using two classic data sets. In both cases, there is good agreement between the model predictions and empirical patterns. Quantification of the mechanisms identified by the models will allow the development of a simple predictive theory linking measures of the intensity of competition with ecosystem‐level properties.     

Towards efficiency in rare disease research: what is distinctive and important?

Characterized by their low prevalence, rare diseases are often chronically debilitating or life threatening. Despite their low prevalence, the aggregate number of individuals suffering from a rare disease is estimated to be nearly 400 million worldwide.Over the past decades, efforts from researchers, clinicians, and pharmaceutical industries have been focused on both the diagnosis and therapy of rare diseases. However, because of the lack of data and medical records for individual rare diseases and the high cost of orphan drug development, only limited progress has been achieved. In recent years, the rapid development of next-generation sequencing(NGS)-based technologies, as well as the popularity of precision medicine has facilitated a better understanding of rare diseases and their molecular etiology. As a result, molecular subclassification can be identified within each disease more clearly, significantly improving diagnostic accuracy. However, providing appropriate care for patients with rare diseases is still an enormous challenge. In this review, we provide a brief introduction to the challenges of rare disease research and make suggestions on where and how our efforts should be focused.     

Is metabolic rate a universal ‘pacemaker’ for biological processes?

A common, long‐held belief is that metabolic rate drives the rates of various biological, ecological and evolutionary processes. Although this metabolic pacemaker view (as assumed by the recent, influential ‘metabolic theory of ecology’) may be true in at least some situations (e.g. those involving moderate temperature effects or physiological processes closely linked to metabolism, such as heartbeat and breathing rate), it suffers from several major limitations, including: (i) it is supported chiefly by indirect, correlational evidence (e.g. similarities between the body‐size and temperature scaling of metabolic rate and that of other biological processes, which are not always observed) – direct, mechanistic or experimental support is scarce and much needed; (ii) it is contradicted by abundant evidence showing that various intrinsic and extrinsic factors (e.g. hormonal action and temperature changes) can dissociate the rates of metabolism, growth, development and other biological processes; (iii) there are many examples where metabolic rate appears to respond to, rather than drive the rates of various other biological processes (e.g. ontogenetic growth, food intake and locomotor activity); (iv) there are additional examples where metabolic rate appears to be unrelated to the rate of a biological process (e.g. ageing, circadian rhythms, and molecular evolution); and (v) the theoretical foundation for the metabolic pacemaker view focuses only on the energetic control of biological processes, while ignoring the importance of informational control, as mediated by various genetic, cellular, and neuroendocrine regulatory systems. I argue that a comprehensive understanding of the pace of life must include how biological activities depend on both energy and information and their environmentally sensitive interaction. This conclusion is supported by extensive evidence showing that hormones and other regulatory factors and signalling systems coordinate the processes of growth, metabolism and food intake in adaptive ways that are responsive to an organism's internal and external conditions. Metabolic rate does not merely dictate growth rate, but is coadjusted with it. Energy and information use are intimately intertwined in living systems: biological signalling pathways both control and respond to the energetic state of an organism. This review also reveals that we have much to learn about the temporal structure of the pace of life. Are its component processes highly integrated and synchronized, or are they loosely connected and often discordant? And what causes the level of coordination that we see? These questions are of great theoretical and practical importance.     

Native topology or specific interactions: what is more important for protein folding?

Fifty-five molecular dynamics runs of two three-stranded antiparallel beta-sheet peptides were performed to investigate the relative importance of amino acid sequence and native topology. The two peptides consist of 20 residues each and have a sequence identity of 15 %. One peptide has Gly-Ser (GS) at both turns, while the other has d-Pro-Gly ((D)PG). The simulations successfully reproduce the NMR solution conformations, irrespective of the starting structure. The large number of folding events sampled along the trajectories at 360 K (total simulation time of about 5 micros) yield a projection of the free-energy landscape onto two significant progress variables. The two peptides have compact denatured states, similar free-energy surfaces, and folding pathways that involve the formation of a beta-hairpin followed by consolidation of the unstructured strand. For the GS peptide, there are 33 folding events that start by the formation of the 2-3 beta-hairpin and 17 with first the 1-2 beta-hairpin. For the (D)PG peptide, the statistical predominance is opposite, 16 and 47 folding events start from the 2-3 beta-hairpin and the 1-2 beta-hairpin, respectively. These simulation results indicate that the overall shape of the free-energy surface is defined primarily by the native-state topology, in agreement with an ever-increasing amount of experimental and theoretical evidence, while the amino acid sequence determines the statistically predominant order of the events.     

Identifying your enemies – could envelope stress trigger microbial immunity?

Microbes utilize defence systems with fundamental similarities to our innate and adaptive immune responses to protect themselves from harmful invaders. One system, made up of CRISPR loci & Cas proteins, incorporates recognizable features from the genomes of viruses (bacteriophages) and plasmids into bacterial genomes, where they are later used to direct a ribonucleoprotein complex to destroy invading nucleic acids upon re-exposure. CRISPR-mediated defence against invasive nucleic acids is found in most archaea and many eubacteria. Many aspects of this newly described defence system have not been worked out, including the molecular mechanisms by which foreign nucleic acids are incorporated into microbial genomes during adaption and destroyed during interference. In this issue of Molecular Microbiology, DeLisa and colleagues provide insight into how this form of microbial immunity might be regulated in eubacteria. They demonstrate that Escherichia coli CRISPR-mediated immunity requires the presence of the BaeSR two-component system under certain conditions. Since BaeSR regulate an envelope stress response, their data imply that immunity against invading, foreign nucleic acids may be somehow linked to stresses to the bacterial membrane. These observations will help pave the way to understanding how and when CRISPR-based immunity may be important in driving evolution and adaptation in eubacteria.     

N for AsN – O for StrOcture? A strand–loop–strand motif for prokaryotic O‐glycosylation

So far, it has not been possible to identify a general sequence motif for O-glycosylation in bacteria. In this issue, Charbonneau et al. (2012) demonstrate why O-glycosylation is mediated by a 13-residue strand-loop-strand motif which is part of a 19-residue imperfect repeat in the passenger domain of bacterial autotransporters. This motif provides a convenient 'glycosylation cassette' and raises intriguing questions about the structural regulation of the glycosylation pathway.     

How important is DNA replication for mutagenesis?

Rates of mutation and substitution in mammals are generally greater in the germ lines of males. This is usually explained as resulting from the larger number of germ cell divisions during spermatogenesis compared with oogenesis, with the assumption made that mutations occur primarily during DNA replication. However, the rate of cell division is not the only difference between male and female germ lines, and mechanisms are known that can give rise to mutations independently of DNA replication. We investigate the possibility that there are other causes of male-biased mutation. First, we show that patterns of variation at approximately 5,200 short tandem repeat (STR) loci indicate a higher mutation rate in males. We estimate a ratio of male-to-female mutation rates of approximately 1.9. This is significantly greater than 1 and supports a greater rate of mutation in males, affecting the evolution of these loci. Second, we show that there are chromosome-specific patterns of nucleotide and dinucleotide composition in mammals that have been shaped by mutation at CpG dinucleotides. Comparable patterns occur in birds. In mammals, male germ lines are more methylated than female germ lines, and these patterns indicate that differential methylation has played a role in male-biased vertebrate evolution. However, estimates of male mutation bias obtained from both classes of mutation are substantially lower than estimates of cell division bias from anatomical data. This discrepancy, along with published data indicating slipped-strand mispairing arising at STR loci in nonreplicating DNA, suggests that a substantial percentage of mutation may occur in nonreplicating DNA.