Deleterious epistatic interactions between electron transport system protein-coding loci in the copepod Tigriopus californicus

The nature of epistatic interactions between genes encoding interacting proteins in hybrid organisms can have important implications for the evolution of postzygotic reproductive isolation and speciation. At this point very little is known about the fitness differences caused by specific closely interacting but evolutionarily divergent proteins in hybrids between populations or species. The intertidal copepod Tigriopus californicus provides an excellent model in which to study such interactions because the species range includes numerous genetically divergent populations that are still capable of being crossed in the laboratory. Here, the effect on fitness due to the interactions of three complex III proteins of the electron transport system in F2 hybrid copepods resulting from crosses of a pair of divergent populations is examined. Significant deviations from Mendelian inheritance are observed for each of the three genes in F2 hybrid adults but not in nauplii (larvae). The two-way interactions between these genes also have a significant impact upon the viability of these hybrid copepods. Dominance appears to play an important role in mediating the interactions between these loci as deviations are caused by heterozygote/homozygote deleterious interactions. These results suggest that the fitness consequences of the interactions of these three complex III-associated genes could influence reproductive isolation in this system.     

Cortical control of microtubule stability and polarization

In both dividing and interphase cells, microtubules are remodeled in response to signal transduction pathways triggered by a variety of stimuli. Members of the Rho family of small GTPases have emerged as key intermediates in transmitting signals to cortical factors that mediate capture of dynamic microtubules at specific sites. The specificity of cortical capture appears to be controlled by microtubule tip proteins and cortical receptors that bind these proteins. Recent studies suggest that some of the proteins interacting with microtubule tips behave as bridging proteins between the microtubule tip proteins and their cortical receptors. Such bridging proteins may enhance cortical capture of microtubules directly or indirectly through interactions with the actin cytoskeleton.     

Kin selection and coefficients of relatedness in family-structured populations with inbreeding

We consider family specific fitnesses that depend on mixed strategies of two basic phenotypes or behaviours. Pairwise interactions are assumed, but they are restricted to occur between sibs. To study the change in frequency of a rare mutant allele, we consider two different forms of weak selection, one applied through small differences in genotypic values determining individual mixed strategies, the other through small differences in viabilities according to the behaviours chosen by interacting sibs. Under these two specific forms of weak selection, we deduce conditions for initial increase in frequency of a rare mutant allele for autosomal genes in the partial selfing model as well as autosomal and sex-linked genes in the partial sib-mating model with selection before mating or selection after mating. With small differences in mixed strategies, we show that conditions for protection of a mutant allele are tantamount to conditions for initial increase in frequency obtained in additive kin selection models. With particular reference to altruism versus selfishness, we provide explicit ranges of values for the selfing or sib-mating rate based on a fixed cost-benefit ratio and the dominance scheme that allow the spreading of a rare mutant allele into the population. This study confirms that more inbreeding does not necessarily promote the evolution of altruism. Under the hypothesis of small differences in viabilities, the situation is much more intricate unless an additive model is assumed. In general however, conditions for initial increase in frequency of a mutant allele can be obtained in terms of fitness effects that depend on the genotypes of interacting individuals or their mates and generalized conditional coefficients of relatedness according to the inbreeding condition of the interacting individuals.     

Protein-protein interactions more conserved within species than across species

Experimental high-throughput studies of protein-protein interactions are beginning to provide enough data for comprehensive computational studies. Today, about ten large data sets, each with thousands of interacting pairs, coarsely sample the interactions in fly, human, worm, and yeast. Another about 55,000 pairs of interacting proteins have been identified by more careful, detailed biochemical experiments. Most interactions are experimentally observed in prokaryotes and simple eukaryotes; very few interactions are observed in higher eukaryotes such as mammals. It is commonly assumed that pathways in mammals can be inferred through homology to model organisms, e.g. the experimental observation that two yeast proteins interact is transferred to infer that the two corresponding proteins in human also interact. Two pairs for which the interaction is conserved are often described as interologs. The goal of this investigation was a large-scale comprehensive analysis of such inferences, i.e. of the evolutionary conservation of interologs. Here, we introduced a novel score for measuring the overlap between protein-protein interaction data sets. This measure appeared to reflect the overall quality of the data and was the basis for our two surprising results from our large-scale analysis. Firstly, homology-based inferences of physical protein-protein interactions appeared far less successful than expected. In fact, such inferences were accurate only for extremely high levels of sequence similarity. Secondly, and most surprisingly, the identification of interacting partners through sequence similarity was significantly more reliable for protein pairs within the same organism than for pairs between species. Our analysis underlined that the discrepancies between different datasets are large, even when using the same type of experiment on the same organism. This reality considerably constrains the power of homology-based transfer of interactions. In particular, the experimental probing of interactions in distant model organisms has to be undertaken with some caution. More comprehensive images of protein-protein networks will require the combination of many high-throughput methods, including in silico inferences and predictions. http://www.rostlab.org/results/2006/ppi_homology/     

Positive interactions by cushion plants in high mountains: fact or artifact?

Aims Positive interactions are defined as non-trophic interactions where at least one of the interacting species is benefited in terms of fitness and the other remains unaffected. Nevertheless, the bidirectional feedbacks between species may be positive, neutral or negative. Thus, if facilitated species induce negative effects on their 'nurses', the assumed definition of positive interactions could be reconsidered.Methods We assessed if ecological interactions between cushions of Azorella madreporica and their facilitated species are positive. Specifically, we tested if cover of facilitated species has any costs for cushion plants from an ecophysiological perspective, and if these costs increase with the amount of cover of facilitated species. In addition, through pathway analysis and correlations, we assessed if cover and richness of facilitated species have a direct and/or indirect effect on the fitness of cushion plants.Important findings We found that facilitated plant species induced a significant cost for their nurses (cushion plants), and this cost increases with cover of the facilitated species. Additionally, the facilitated species exert a strong direct negative effect on the cushion's fitness and a moderate indirect negative cost evident through the nutrient status and physiological performance of cushion plants. We thus contribute evidence that positive interactions between high mountain cushion plants of central Chile and their 'facilitated' species may be an artifact more than a fact, especially when bidirectional effects are considered; contrasting with the majority of studies that document only one side of the interaction.     

Structural similarity enhances interaction propensity of proteins

We study statistical properties of interacting protein-like surfaces and predict two strong, related effects: (i) statistically enhanced self-attraction of proteins; (ii) statistically enhanced attraction of proteins with similar structures. The effects originate in the fact that the probability to find a pattern self-match between two identical, even randomly organized interacting protein surfaces is always higher compared with the probability for a pattern match between two different, promiscuous protein surfaces. This theoretical finding explains statistical prevalence of homodimers in protein-protein interaction networks reported earlier. Further, our findings are confirmed by the analysis of curated database of protein complexes that showed highly statistically significant overrepresentation of dimers formed by structurally similar proteins with highly divergent sequences ("superfamily heterodimers"). We suggest that promiscuous homodimeric interactions pose strong competitive interactions for heterodimers evolved from homodimers. Such evolutionary bottleneck is overcome using the negative design evolutionary pressure applied against promiscuous homodimer formation. This is achieved through the formation of highly specific contacts formed by charged residues as demonstrated both in model and real superfamily heterodimers.     

CH/π interactions of π-system of acetylacetonato chelate ring: Comparison of CH/π interactions of Ni(II)-acetylacetonato chelate and benzene rings

The calculations have been done for CH/π interaction with π-system of Ni(II)-acetylacetonato chelate ring. The results show that there is an attractive electrostatic interaction, while dispersion component is a major source of attractive interacting energies. The interaction was compared with CH/π interaction between two benzene rings. The comparison shows that two interactions are quite similar, enabling to estimate the energy of CH/π interaction with π-system of Ni(II)-acetylacetonato chelate ring to be about 10.5 kJ/mol. The results indicate that CH/π interactions of chelate ring in various molecular systems can be as important as CH/π interactions of phenyl ring.     

Are Olfactory Receptors Really Olfactive?

Any living organism interacts with and responds specifically to environmental molecules by expressing specific olfactory receptors. In this paper, this specificity will be first examined in causal terms with particular emphasis on the mechanisms controlling olfactory gene expression, cell-to-cell interactions and odor-decoding processes. However, this type of explanation does not entirely justify the role olfactory receptors have played during evolution, since they are also expressed ectopically in different organs and/or tissues. Homologous olfactory genes have in fact been found in such diverse cells and/or organs as spermatozoa, testis and kidney where they are assumed to act as chemotactic sensors or renin modulators. To justify their functional diversity, homologous olfactory receptors are assumed to share the same basic role: that of conferring a self-identity to cells or tissues under varying environmental conditions. By adopting this standpoint, the functional attribution as olfactory or chemotactic sensors to these receptors should not be seen either as a cause conditioning receptor gene expression, or as a final effect resulting from genetically predetermined programs, but as a direct consequence of the environmental conditions olfactory receptor genes have explored during evolution. The association of odorant patterns with specific environmental or contextual situations makes their relationship semiotically triadic, due to the emergence of an interpretant capable of perceiving odorants as meaningful signs out of a noisy background. This perspective highlights the importance of odorant-receptor relationships as respect to the properties of the interacting partners. It is our contention that only when taken together can these different explanatory strategies provide a realistic account of how olfactory receptor genes have been structurally and functionally modified during evolution.     

FGO: a novel ontology for identification of ligand functional group

Small molecules play crucial role in the modulation of biological functions by interacting with specific macromolecules. Hence small molecule interactions are captured by a variety of experimental methods to estimate and propose correlations between molecular structures to their biological activities. The tremendous expanse in publicly available small molecules is also driving new efforts to better understand interactions involving small molecules particularly in area of drug docking and pharmacogenomics. We have studied and designed a functional group identification system with the associated ontology for it. The functional group identification system can detect the functional group components from given ligand structure with specific coordinate information. Functional group ontology (FGO) proposed by us is a structured classification of chemical functional group which acts as an important source of prior knowledge that may be automatically integrated to support identification, categorization and predictive data analysis tasks. We have used a new annotation method which can be used to construct the original structure from given ontological expression using exact coordinate information. Here, we also discuss about ontology-driven similarity measure of functional groups and uses of such novel ontology for pharmacophore searching and de-novo ligand designing.     

Behavioural phenotype affects social interactions in an animal network

Animal social networks can be extremely complex and are characterized by highly non-random interactions between group members. However, very little is known about the underlying factors affecting interaction preferences, and hence network structure. One possibility is that behavioural differences between individuals, such as how bold or shy they are, can affect the frequency and distribution of their interactions within a network. We tested this using individually marked three-spined sticklebacks (Gasterosteus aculeatus), and found that bold individuals had fewer overall interactions than shy fish, but tended to distribute their interactions more evenly across all group members. Shy fish, on the other hand, tended to associate preferentially with a small number of other group members, leading to a highly skewed distribution of interactions. This was mediated by the reduced tendency of shy fish to move to a new location within the tank when they were interacting with another individual; bold fish showed no such tendency and were equally likely to move irrespective of whether they were interacting or not. The results show that animal social network structure can be affected by the behavioural composition of group members and have important implications for understanding the spread of information and disease in social groups.     

Influence of hydrogen bonds on edge-to-face interactions between pyridine molecules

Edge-to-face interactions between two pyridine molecules and the influence of simultaneous hydrogen bonding of one or both of the pyridines to water on those interactions were studied by analyzing data from ab initio calculations. The results show that the edge-to-face interactions of pyridine dimers that are hydrogen bonded to water are generally stronger than those of non-H-bonded pyridine dimers, especially when the donor pyridine forms a hydrogen bond. The binding energy of the most stable edge-to-face interacting H-bonded pyridine dimer is ?5.05 kcal/mol, while that for the most stable edge-to-face interacting non-H-bonded pyridine dimer is ?3.64 kcal/mol. The interaction energy data obtained in this study cannot be explained solely by the differences in electrostatic potential between pyridine and the pyridine–water dimer. However, the calculated cooperative effect can be predicted using electrostatic potential maps.     

A comprehensive approach to mapping the interacting surfaces of murine amphotropic and feline subgroup B leukemia viruses with their cell surface receptors

Because mutations in envelope glycoproteins of retroviruses or in their cell surface receptors can eliminate function by multiple mechanisms, it has been difficult to unambiguously identify sites for their interactions by site-directed mutagenesis. Recently, we developed a gain-of-function approach to overcome this problem. Our strategy relies on the fact that feline leukemia virus subgroup B (FeLV-B) and amphotropic murine leukemia virus (A-MLV) have closely related gp70 surface envelope glycoproteins and use related Na(+)-dependent phosphate symporters, Pit1 and Pit2, respectively, as their receptors. We previously observed that FeLV-B/A-MLV envelope glycoprotein chimeras spliced between the variable regions VRA and VRB were unable to use Pit1 or Pit2 as a receptor but could efficiently use specific Pit1/Pit2 chimeras. The latter study suggested that the VRA of A-MLV and FeLV-B functionally interact with the presumptive extracellular loops 4 and 5 (ECL4 and -5) of their respective receptors, whereas VRB interacts with ECL2. We also found that FeLV-B gp70 residues F60 and P61 and A-MLV residues Y60 and V61 in the first disulfide-bonded loop of VRA were important for functional interaction with the receptor's ECL4 or -5. We have now extended this approach to identify additional VRA and VRB residues that are involved in receptor recognition. Our studies imply that FeLV-B VRA residues F60 and P61 interact with the Pit1 ECL5 region, whereas VRA residues 66 to 78 interact with Pit1 ECL4. Correspondingly, A-MLV VRA residues Y60 and V61 interact with the Pit2 ECL5 region, whereas residues 66 to 78 interact with Pit2 ECL4. Similar studies that focused on the gp70 VRB implicated residues 129 to 139 as contributing to specific interactions with the receptor ECL2. These results identify three regions of gp70 that interact in a specific manner with distinct portions of their receptors, thereby providing a map of the functionally interacting surfaces.     

Migration of neutrophils through epithelial monolayers

Acute bacterial infections are a major challenge to epithelial linings that interface indirectly with the external world. Such infections are in part fought by neutrophils, which phagocytose and destroy pathogens. Neutrophils arrive at the infection sites by emigrating from small blood vessels and subsequently interacting with and transmigrating across columnar epithelia. There is substantial interest in defining the mechanisms and functional consequences of neutrophil-epithelial interactions. Model systems reveal that specific molecular events are required for appropriate neutrophil-epithelial interactions and, as a result of these interactions, neutrophils may reversibly modulate diverse epithelial functions.     

A statistical model of ChIA-PET data for accurate detection of chromatin 3D interactions

Identification of three-dimensional (3D) interactions between regulatory elements across the genome is crucial to unravel the complex regulatory machinery that orchestrates proliferation and differentiation of cells. ChIA-PET is a novel method to identify such interactions, where physical contacts between regions bound by a specific protein are quantified using next-generation sequencing. However, determining the significance of the observed interaction frequencies in such datasets is challenging, and few methods have been proposed. Despite the fact that regions that are close in linear genomic distance have a much higher tendency to interact by chance, no methods to date are capable of taking such dependency into account. Here, we propose a statistical model taking into account the genomic distance relationship, as well as the general propensity of anchors to be involved in contacts overall. Using both real and simulated data, we show that the previously proposed statistical test, based on Fisher''s exact test, leads to invalid results when data are dependent on genomic distance. We also evaluate our method on previously validated cell-line specific and constitutive 3D interactions, and show that relevant interactions are significant, while avoiding over-estimating the significance of short nearby interactions.     

Analysis of the impact of solvent on contacts prediction in proteins

Background  

The correlated mutations concept is based on the assumption that interacting protein residues coevolve, so that a mutation in one of the interacting counterparts is compensated by a mutation in the other. Approaches based on this concept have been widely used for protein contacts prediction since the 90s. Previously, we have shown that water-mediated interactions play an important role in protein interfaces. We have observed that current "dry" correlated mutations approaches might not properly predict certain interactions in protein interfaces due to the fact that they are water-mediated.     

Electrodynamics of interactions in electrolyte media. Possible consequences in biological functions

Attention is drawn to the fact that electric charge interactions in aqueous electrolyte solutions, such as physiological media, depend not only on the distance between the interacting charges but also on the frequency at which they move. This fact has important consequences for some biological processes, particularly the kinetic ones. Consideration of charge screening, including the dynamic effects, shows that electrical interactions in quasi-physiological systems are effective even above Debye’s length, provided that charges move at frequencies higher than ～250 MHz. For each electrolyte solution, it is possible to define a threshold frequency, the Maxwell frequency, as the point of crossover between a conducting and a dielectric regime in the solution.     

Analysis of protein main-chain solvation as a function of secondary structure

We have analysed the hydration of main-chain carbonyl and amide groups in 24 high-resolution well-refined protein structures as a function of the secondary structure in which these polar groups occur. We find that main-chain atoms in beta-sheets are as hydrated as those in alpha-helices, with most interactions involving "free" amide and carbonyl groups that do not participate in secondary structure hydrogen bonds. The distributions of water molecules around these non-bonded carbonyl groups reflect specific steric interactions due to the local secondary structure. Approximately 20% and 4%, respectively of bonded carbonyl and amide groups interact with solvent. These include interactions with carbonyl groups on the exposed faces of alpha-helices that have been correlated previously with bending of the helix. Water molecules interacting with alpha-helices occur mainly at the amino and carbonyl termini of the helices, in which case the solvent sites maintain the hydrogen bonding by bridging between residues i and i-3 or i-4 at the amino terminus and between i and i+3 or i+4 at the carbonyl terminus. We also see a number of solvent-mediated Ncap and Ccap interactions. The water molecules interacting with beta-sheets occur mainly at the edges, in which case they extend the sheet structure, or at the ends of strands, in which case they extend the beta-ladder. In summary, the solvent networks appear to extend the hydrogen-bonding structure of the secondary structures. In beta-turns, which usually occur at the surface of a protein, exposed amide and carbonyl groups are often hydrated, especially close to glycine residues. Occasionally water molecules form a bridge between residues i and i+3 in the turn and this may provide extra stabilization.     

Evolutionary relationships can be more important than abiotic conditions in predicting the outcome of plant–plant interactions

Positive and negative plant–plant interactions are major processes shaping plant communities. They are affected by environmental conditions and evolutionary relationships among the interacting plants. However, the generality of these factors as drivers of pairwise plant interactions and their combined effects remain virtually unknown. We conducted an observational study to assess how environmental conditions (altitude, temperature, irradiance and rainfall), the dispersal mechanism of beneficiary species and evolutionary relationships affected the co‐occurrence of pairwise interactions in 11 Stipa tenacissima steppes located along an environmental gradient in Spain. We studied 197 pairwise plant–plant interactions involving the two major nurse plants (the resprouting shrub Quercus coccifera and the tussock grass S. tenacissima) found in these communities. The relative importance of the studied factors varied with the nurse species considered. None of the factors studied were good predictors of the co‐ocurrence between S. tenacissima and its neighbours. However, both the dispersal mechanism of the beneficiary species and the phylogenetic distance between interacting species were crucial factors affecting the co‐occurrence between Q. coccifera and its neighbours, while climatic conditions (irradiance) played a secondary role. Values of phylogenetic distance between 207–272.8 Myr led to competition, while values outside this range or fleshy‐fruitness in the beneficiary species led to positive interactions. The low importance of environmental conditions as a general driver of pairwise interactions was caused by the species‐specific response to changes in either rainfall or radiation. This result suggests that factors other than climatic conditions must be included in theoretical models aimed to generally predict the outcome of plant–plant interactions. Our study helps to improve current theory on plant–plant interactions and to understand how these interactions can respond to expected modifications in species composition and climate associated to ongoing global environmental change.