Ribosomal Protein Mutations Induce Autophagy through S6 Kinase Inhibition of the Insulin Pathway

Mutations affecting the ribosome lead to several diseases known as ribosomopathies, with phenotypes that include growth defects, cytopenia, and bone marrow failure. Diamond-Blackfan anemia (DBA), for example, is a pure red cell aplasia linked to the mutation of ribosomal protein (RP) genes. Here we show the knock-down of the DBA-linked RPS19 gene induces the cellular self-digestion process of autophagy, a pathway critical for proper hematopoiesis. We also observe an increase of autophagy in cells derived from DBA patients, in CD34⁺ erythrocyte progenitor cells with RPS19 knock down, in the red blood cells of zebrafish embryos with RP-deficiency, and in cells from patients with Shwachman-Diamond syndrome (SDS). The loss of RPs in all these models results in a marked increase in S6 kinase phosphorylation that we find is triggered by an increase in reactive oxygen species (ROS). We show that this increase in S6 kinase phosphorylation inhibits the insulin pathway and AKT phosphorylation activity through a mechanism reminiscent of insulin resistance. While stimulating RP-deficient cells with insulin reduces autophagy, antioxidant treatment reduces S6 kinase phosphorylation, autophagy, and stabilization of the p53 tumor suppressor. Our data suggest that RP loss promotes the aberrant activation of both S6 kinase and p53 by increasing intracellular ROS levels. The deregulation of these signaling pathways is likely playing a major role in the pathophysiology of ribosomopathies.     

Differential gene expression and phenotypic plasticity in behavioural castes of the primitively eusocial wasp, Polistes canadensis

Understanding how a single genome can produce a variety of different phenotypes is of fundamental importance in evolutionary and developmental biology. One of the most striking examples of phenotypic plasticity is the female caste system found in eusocial insects, where variation in reproductive (queens) and non-reproductive (workers) phenotypes results in a broad spectrum of caste types, ranging from behavioural through to morphological castes. Recent advances in genomic techniques allow novel comparisons on the nature of caste phenotypes to be made at the level of the genes in organisms for which there is little genome information, facilitating new approaches in studying social evolution and behaviour. Using the paper wasp Polistes canadensis as a model system, we investigated for the first time how behavioural castes in primitively eusocial insect societies are associated with differential expression of shared genes. We found that queens and newly emerged females express gene expression patterns that are distinct from each other whilst workers generally expressed intermediate patterns, as predicted by Polistes biology. We compared caste-associated genes in P. canadensis with those expressed in adult queens and workers of more advanced eusocial societies, which represent four independent origins of eusociality. Nine genes were conserved across the four taxa, although their patterns of expression and putative functions varied. Thus, we identify several genes that are putatively of evolutionary importance in the molecular biology that underlies a number of caste systems of independent evolutionary origin.     

Molecular paternity determination in captive bonobos and the impact of inbreeding on infant mortality

Inbreeding and the loss of genetic diversity may lower fitness and reduce the potential for a population to adapt to changing environments. In small populations, for example in captive populations or populations of endangered species, this can have considerable consequences for their survival. We investigated the effects of inbreeding on infant mortality in the world captive population of bonobos Pan paniscus . Using a combination of studbook data and high-quality pedigree data from genotyped individuals, inbreeding information was available for 142 captive-born individuals. For the determination of paternities that were unresolved in the studbook, nuclear microsatellite DNA was amplified from hair and blood samples using the Great Ape Kit and PowerPlex^® 16 System. In total, 54 bonobos (17 offspring and their putative parents) were genotyped at eight tetranucleotide repeat microsatellite loci. Inbreeding coefficients were calculated for each individual for whom paternity was confirmed by either studbook data or DNA analysis. We found significantly higher infant mortality in inbred offspring compared with non-inbred offspring, suggesting that inbreeding reduces infant survival in captive bonobos. In addition, we argue that the total magnitude of inbreeding depression is probably underestimated in this captive population. In conclusion, even though the breeding programme of captive bonobos is aimed at avoiding inbreeding, closely related individuals do occasionally produce offspring that do show inbreeding depression. There is, however, no indication that this currently threatens the long-time survival of the captive population of bonobos.     

The organisation of larval feeding in bumblebees (Hymenoptera,Apidae) and its significance to caste differentiation

Summary. In pollen-storing bumblebees, the rate at which workers nourish larvae has been proposed to be the main factor influencing caste differentiation since workers feed prospective queens more frequently and longer than worker larvae during the last instars. In order to determine how the frequency of feedings is established small groups of Bombus terrestris larvae were either subjected to starvation or nourished regularly by workers. Experimentally starved larvae were fed significantly earlier and more often than control larvae. Behavioural observations provide evidence for the existence of a stimulus of larval origin that releases feeding behaviour in workers. Intentional inspections in the sense of a recognisable and functional behaviour intended to organise the feeding process were never observed. We argue that worker inspections are not required for the adequate maintenance of larvae and that a simple stimulus-response chain appears to be sufficient to regulate feeding behaviour at the individual and the colony level in bumblebees. Furthermore, hand-rearing experiments with female larvae indicate that queen rearing is not dependent on a high frequency of feedings in itself, nor is worker development induced by larval deprivation. This makes it unlikely that workers impose a caste-specific frequency of feedings on larvae in order to actively control or manipulate caste development. Since caste fate seems to be predetermined early in larval life, we propose that early caste-specific differences in development are reflected in the physiology of the larvae and the associated nutritional needs to which workers respond accordingly. Consequently, caste-specific differences in feeding frequencies are a result, but not the cause of differences in development.     

Implications of an individualistic lifestyle for species conservation: lessons from jealous beasts

Polecat populations show a very low genetic diversity and a high inbreeding coefficient. Furthermore, the estimate of effective population size is alarmingly low. Polecats Mustela putorius populations are structured into scattered breeding sub-units usually made up of one male and two females, according to a polygynous mating system. Because a strict spatio-temporal segregation was observed between males and females, we propose to call individualistic such species. We suggest that the solitary habits of individualistic species may result in or worsen a high inbreeding and exacerbate their conservation issue, a crucial perspective for critically endangered species such as the European mink.     

The composition of larval food and the significance of exocrine secretions in the bumblebee Bombus terrestris

Summary: This paper describes a study on the relation between the composition of larval food and the development of female castes in bumblebees. The first aim was to evaluate the significance of glandular secretions in the larval diet as a possible factor involved in larval feeding and caste differentiation. Small amounts of proteinaceous secretions were found to be added during the ingestion of sucrose but not while discharging food to the larvae. It is discussed that these secretions are digestive in function rather than food additives that would possibly play a role in the process of caste differentiation.¶Secondly, a comparative analysis was made of the general composition of food samples obtained from larvae of different castes and ages and from various periods in the social development of the colony. No significant differences in the total amount of pollen, sucrose and protein were detected between the castes or different age groups. Unlike honeybee workers, individual bumblebee workers did not change the composition of the diet they supplied to the brood in relation to their own age, nor to the social development of the colony. These findings suggest that all larvae receive the same nourishment during their total development and indicate that differences in development between queen larvae and worker larvae are neither caused by variations nor by a qualitative modification of their food with respect to the amount of pollen, protein and carbohydrates.     

A brief note on the effects of novel enrichment on an unwanted behaviour of captive bonobos

Animals in captivity may show undesirable behaviour when they are not sufficiently challenged, making it essential for their well-being to provide daily enrichment to zoo animals. Primates need a regular replacement with novel enrichment objects to prevent them from getting bored and look for challenging situations which might be even more undesirable. A socially housed group of bonobos showed behavioural problems such as stealing and rough handling and playing with a newborn infant in the group. To study whether providing novel environmental enrichment has an effect on this phenomenon we performed an experiment where we observed the change in behaviour in the presence of familiar and novel enrichment devices. When provided with novel enrichments, the general activity of the group increased. Simultaneously, these novel behavioural challenges significantly decreased the frequency of taking the newborn infant from its mother. Our results confirm previous findings that continuous application of new enrichments is necessary for providing sensory stimulation to primates as it promotes their well-being and indirectly might influence breeding success as well.