Estimating sex-specific dispersal rates with autosomal markers in hierarchically structured populations

Abstract –A recent study suggests that sex-specific dispersal rates can be quantitatively estimated on the basis of sex- and state-specific (pre- vs. postdispersal) F -statistics. In the present paper, we extend this approach to account for the hierarchical structure of natural populations, and we validate it through individual-based simulations. The model is applied to an empirical data set consisting of 536 individuals (males, females, and predispersal juveniles) of greater white-toothed shrews ( Crocidura russula ), sampled according to a hierarchical design and typed for seven autosomal microsatellite loci. From this dataset, dispersal is significantly female biased at the local scale (breeding-group level), but not at the larger scale (among local populations). We argue that selective pressures on dispersal are likely to depend on the spatial scale considered, and that short-distance dispersal should mainly respond to kin interactions (inbreeding or kin competition avoidance), which exert differential pressure on males and females.     

Isoform specific function of calpain 2 in regulating membrane protrusion

Previous studies have demonstrated a role for calpains in cell migration through their capacity to regulate focal adhesion dynamics and rear retraction. In this study, we provide evidence that calpains also modulate membrane protrusion activity in fibroblasts. We find that an immortalized Capn4(-/-) fibroblast line displays an altered morphology, characterized by numerous thin membrane projections and increased transient membrane activity. Furthermore, we show that protrusion kinetics of lamellipodia at the leading edge are improperly regulated in Capn4(-/-) cells, leading to impaired net forward lamellipodial extension. To address the isoform specific functions of calpain 1 and calpain 2 during cell protrusion, we stably introduced small interfering RNAs (siRNAs) targeting each isoform into a fibroblast cell line. Despite a loss in calpain 1 activity, calpain 1 knockdown cells show normal morphology and membrane protrusion dynamics. However, cells in which calpain 2 is knocked down are characterized by a protrusive morphology, increased transient membrane activity and altered protrusion kinetics, similar to the Capn4(-/-) fibroblasts. Additionally, we find that calpain 2, but not calpain 1, is required for proteolysis of the cytoskeletal and focal adhesion proteins FAK, paxillin, spectrin, and talin. Together, our findings support a novel role for calpain 2 in limiting membrane protrusions and in regulating lamellipodial dynamics at the leading edge of migrating cells.     

Conformational and inframolecular studies of the protonation of adenophostin analogues lacking the adenine moiety

Four adenophostin analogues lacking the adenine moiety were subjected to 31P- and 1H-NMR titrations in order to determine the acid-base behaviour of the individual ionisable groups of the molecules and the complex interplay of intramolecular interactions resulting from the protonation process. For the two trisphosphorylated compounds, the curve pattern of the phosphorus nuclei corresponds to the superimposition of the titration curves of a monophosphorylated polyol and a polyol carrying two vicinal phosphates, suggesting that the two phosphate moieties behave independently. Also, the general shape of 1H-NMR titration curves of the studied compounds is very close to that of adenophostin A, indicating that the adenine moiety does not specifically interact with the phosphorylated sugar moieties. The curves show, however, that both trisphosphorylated compounds adopt slightly different preferential conformations which could contribute to explain the difference in their affinity for Ins(1,4,5)P3 receptor. Their macroscopic as well as the microscopic protonation constants are higher than those of adenophostin A, indicating that the adenine moiety plays a base-weakening effect on the phosphate groups. Further analysis of the microscopic protonation constants confirms that the compound whose conformation is the closest to that of adenophostin A also shows the highest biological activity. The two bisphosphorylated analogues studied behave very similarly, suggesting that the deletion of the hydroxymethyl group on the pentafuranosyl ring only weakly influences the protonation process of the phosphate groups that bear the glucopyranose moiety.     

Evidence of unique genotypes of beak and feather disease virus in southern Africa

Psittacine beak and feather disease (PBFD), caused by Beak and feather disease virus (BFDV), is the most significant infectious disease in psittacines. PBFD is thought to have originated in Australia but is now found worldwide; in Africa, it threatens the survival of the indigenous endangered Cape parrot and the vulnerable black-cheeked lovebird. We investigated the genetic diversity of putative BFDVs from southern Africa. Feathers and heparinized blood samples were collected from 27 birds representing 9 psittacine species, all showing clinical signs of PBFD. DNA extracted from these samples was used for PCR amplification of the putative BFDV coat protein (CP) gene. The nucleotide sequences of the CP genes of 19 unique BFDV isolates were determined and compared with the 24 previously described sequences of BFDV isolates from Australasia and America. Phylogenetic analysis revealed eight BFDV lineages, with the southern African isolates representing at least three distinctly unique genotypes; 10 complete genome sequences were determined, representing at least one of every distinct lineage. The nucleotide diversity of the southern African isolates was calculated to be 6.4% and is comparable to that found in Australia and New Zealand. BFDVs in southern Africa have, however, diverged substantially from viruses found in other parts of the world, as the average distance between the southern African isolates and BFDV isolates from Australia ranged from 8.3 to 10.8%. In addition to point mutations, recombination was found to contribute substantially to the level of genetic variation among BFDVs, with evidence of recombination in all but one of the genomes analyzed.     

Cell type-dependent, infection-induced, aberrant DNA methylation in gastric cancer

Epigenetic changes correspond to heritable modifications of the chromatin structure, which do not involve any alteration of the DNA sequence but nonetheless affect gene expression. These mechanisms play an important role in cell differentiation, but aberrant occurrences are also associated with a number of diseases, including cancer and neural development disorders.In particular, aberrant DNA methylation induced by H. Pylori has been found to be a significant risk factor in gastric cancer. To investigate the sensitivity of different genes and cell types to this infection, a computational model of methylation in gastric crypts is developed.In this article, we review existing results from physical experiments and outline their limitations, before presenting the computational model and investigating the influence of its parameters.     

An interaction between U2AF 65 and CF I(m) links the splicing and 3' end processing machineries

The protein factor U2 snRNP Auxiliary Factor (U2AF) 65 is an essential component required for splicing and involved in the coupling of splicing and 3' end processing of vertebrate pre-mRNAs. Here we have addressed the mechanisms by which U2AF 65 stimulates pre-mRNA 3' end processing. We identify an arginine/serine-rich region of U2AF 65 that mediates an interaction with an RS-like alternating charge domain of the 59 kDa subunit of the human cleavage factor I (CF I(m)), an essential 3' processing factor that functions at an early step in the recognition of the 3' end processing signal. Tethered functional analysis shows that the U2AF 65/CF I(m) 59 interaction stimulates in vitro 3' end cleavage and polyadenylation. These results therefore uncover a direct role of the U2AF 65/CF I(m) 59 interaction in the functional coordination of splicing and 3' end processing.     

Population demography and the evolution of helping behaviors

Limited dispersal may favor the evolution of helping behaviors between relatives as it increases their relatedness, and it may inhibit such evolution as it increases local competition between these relatives. Here, we explore one way out of this dilemma: if the helping behavior allows groups to expand in size, then the kin-competition pressure opposing its evolution can be greatly reduced. We explore the effects of two kinds of stochasticity allowing for such deme expansion. First, we study the evolution of helping under environmental stochasticity that may induce complete patch extinction. Helping evolves if it results in a decrease in the probability of extinction or if it enhances the rate of patch recolonization through propagules formed by fission of nonextinct groups. This mode of dispersal is indeed commonly found in social species. Second, we consider the evolution of helping in the presence of demographic stochasticity. When fecundity is below its value maximizing deme size (undersaturation), helping evolves, but under stringent conditions unless positive density dependence (Allee effect) interferes with demographic stochasticity. When fecundity is above its value maximizing deme size (oversaturation), helping may also evolve, but only if it reduces negative density-dependent competition.     

Low Y chromosome variation in Saudi-Arabian hamadryas baboons (Papio hamadryas hamadryas)

It is important to characterise the amount of variation on the mammalian Y chromosome in order to assess its potential for use in evolutionary studies. We report very low levels of polymorphism on the Y chromosome of Saudi-Arabian hamadryas baboons, Papio hamadryas hamadryas. We found no segregating sites on the Y, despite sequence analysis of 3 kb noncontiguous intron sequence in 16 males with divergent autosomal microsatellite genotypes, and a further analysis of 1.1 kb intron sequence in 97 males from four populations by SSCP. In addition, we tested seven human-derived Y-linked microsatellites in baboons. Only four of these loci were male-specific and only one was polymorphic in our 97 male sample set. Polymorphism on the Y chromosome of Arabian hamadryas appears to be low compared to other primate species for which data are available (eg humans, chimpanzees and bonobos). Low effective population size (Ne) of paternal genes due to polygyny and female-biased adult sex ratio is a potential reason for low Y chromosome variation in this species. However, low Ne for the Y should be counterbalanced to some extent by the species' atypical pattern of male philopatry and female-biased dispersal. Allelic richness averaged over seven loci was not significantly different between an African and an Arabian population, suggesting that loss of variation during the colonisation of Arabia does not explain low Y variation. Finally, in the absence of nucleotide polymorphism, it is unclear to what extent selection could be responsible for low Y variation in this species.     

Proteolysis of cortactin by calpain regulates membrane protrusion during cell migration

Calpain 2 regulates membrane protrusion during cell migration. However, relevant substrates that mediate the effects of calpain on protrusion have not been identified. One potential candidate substrate is the actin binding protein cortactin. Cortactin is a Src substrate that drives actin polymerization by activating the Arp2/3 complex and also stabilizes the cortical actin network. We now provide evidence that proteolysis of cortactin by calpain 2 regulates membrane protrusion dynamics during cell migration. We show that cortactin is a calpain 2 substrate in fibroblasts and that the preferred cleavage site occurs in a region between the actin binding repeats and the alpha-helical domain. We have generated a mutant cortactin that is resistant to calpain proteolysis but retains other biochemical properties of cortactin. Expression of the calpain-resistant cortactin, but not wild-type cortactin, impairs cell migration and increases transient membrane protrusion, suggesting that calpain proteolysis of cortactin limits membrane protrusions and regulates migration in fibroblasts. Furthermore, the enhanced protrusion observed with the calpain-resistant cortactin requires both the Arp2/3 binding site and the Src homology 3 domain of cortactin. Together, these findings suggest a novel role for calpain-mediated proteolysis of cortactin in regulating membrane protrusion dynamics during cell migration.