A systems approach to animal communication

Why animal communication displays are so complex and how they have evolved are active foci of research with a long and rich history. Progress towards an evolutionary analysis of signal complexity, however, has been constrained by a lack of hypotheses to explain similarities and/or differences in signalling systems across taxa. To address this, we advocate incorporating a systems approach into studies of animal communication—an approach that includes comprehensive experimental designs and data collection in combination with the implementation of systems concepts and tools. A systems approach evaluates overall display architecture, including how components interact to alter function, and how function varies in different states of the system. We provide a brief overview of the current state of the field, including a focus on select studies that highlight the dynamic nature of animal signalling. We then introduce core concepts from systems biology (redundancy, degeneracy, pluripotentiality, and modularity) and discuss their relationships with system properties (e.g. robustness, flexibility, evolvability). We translate systems concepts into an animal communication framework and accentuate their utility through a case study. Finally, we demonstrate how consideration of the system-level organization of animal communication poses new practical research questions that will aid our understanding of how and why animal displays are so complex.     

Multimodal signalling in the North American barn swallow: a phenotype network approach

Complex signals, involving multiple components within and across modalities, are common in animal communication. However, decomposing complex signals into traits and their interactions remains a fundamental challenge for studies of phenotype evolution. We apply a novel phenotype network approach for studying complex signal evolution in the North American barn swallow (Hirundo rustica erythrogaster). We integrate model testing with correlation-based phenotype networks to infer the contributions of female mate choice and male–male competition to the evolution of barn swallow communication. Overall, the best predictors of mate choice were distinct from those for competition, while moderate functional overlap suggests males and females use some of the same traits to assess potential mates and rivals. We interpret model results in the context of a network of traits, and suggest this approach allows researchers a more nuanced view of trait clustering patterns that informs new hypotheses about the evolution of communication systems.     

Toward a universal measure of robustness across model organs and systems

The development of an individual must be capable of resisting the harmful effects of internal and external perturbations. This capacity, called robustness, can make the difference between normal variation and disease. Some systems and organs are more resilient in their capacity to correct the effects of internal disturbances such as mutations. Similarly, organs and organisms differ in their capacity to be resilient against external disturbances, such as changes in temperature. Furthermore, all developmental systems must be somewhat flexible to permit evolutionary change, and understanding robustness requires a comparative framework. Over the last decades, most research on developmental robustness has been focusing on specific model systems and organs. Hence, we lack tools that would allow cross-species and cross-organ comparisons. Here, we emphasize the need for a uniform framework to experimentally test and quantify robustness across study systems and suggest that the analysis of fluctuating asymmetry might be a powerful proxy to do so. Such a comparative framework will ultimately help to resolve why and how organs of the same and different species differ in their sensitivity to internal (e.g., mutations) and external (e.g., temperature) perturbations and at what level of biological organization buffering capacities exist and therefore create robustness of the developmental system.     

Towards a systems biology approach to understanding seed dormancy and germination

Seed germination is the first adaptive decision in the development of many land plants. Advances in genetics and molecular physiology have taught us much about the control of germination using the model plant Arabidopsis thaliana. Here we review the current state of the art with an emphasis on mechanistic considerations and explore the potential impact of a systems biology approach to the problem.     

Persistent degenerative changes in thymic organ function revealed by an inducible model of organ regrowth

The thymus is the most rapidly aging tissue in the body, with progressive atrophy beginning as early as birth and not later than adolescence. Latent regenerative potential exists in the atrophic thymus, because certain stimuli can induce quantitative regrowth, but qualitative function of T lymphocytes produced by the regenerated organ has not been fully assessed. Using a genome-wide computational approach, we show that accelerated thymic aging is primarily a function of stromal cells, and that while overall cellularity of the thymus can be restored, many other aspects of thymic function cannot. Medullary islet complexity and tissue-restricted antigen expression decrease with age, representing potential mechanisms for age-related increases in autoimmune disease, but neither of these is restored by induced regrowth, suggesting that new T cells produced by the regrown thymus will probably include more autoreactive cells. Global analysis of stromal gene expression profiles implicates widespread changes in Wnt signaling as the most significant hallmark of degeneration, changes that once again persist even at peak regrowth. Consistent with the permanent nature of age-related molecular changes in stromal cells, induced thymic regrowth is not durable, with the regrown organ returning to an atrophic state within 2 weeks of reaching peak size. Our findings indicate that while quantitative regrowth of the thymus is achievable, the changes associated with aging persist, including potential negative implications for autoimmunity.     

A systems biology approach to understanding elevated serum alanine transaminase levels in a clinical trial with ximelagatran

Ximelagatran was developed for the prevention and treatment of thromboembolic conditions. However, in long-term clinical trials with ximelagatran, the liver injury marker, alanine aminotransferase (ALT) increased in some patients. Analysis of plasma samples from 134 patients was carried out using proteomic and metabolomic platforms, with the aim of finding predictive biomarkers to explain the ALT elevation. Analytes that were changed after ximelagatran treatment included 3-hydroxybutyrate, pyruvic acid, CSF1R, Gc-globulin, L-glutamine, protein S and alanine, etc. Two of these analytes (pyruvic acid and CSF1R) were studied further in human cell cultures in vitro with ximelagatran. A systems biology approach applied in this study proved to be successful in generating new hypotheses for an unknown mechanism of toxicity.     

Diel variation in a dynamic sexual display and its association with female mate-searching behaviour

Dynamic sexual signals often show a diel rhythm and may vary substantially with time of day. Diel and short-term fluctuations in such sexual signals pose a puzzle for condition capture models of mate choice, which assume a female preference for male traits that reliably reflect a male's quality. Here we experimentally manipulated the food supply of individual male field crickets Gryllus campestris in their natural habitat in two consecutive seasons to determine (i) the effect of male nutritional condition on the fine-scaled variation of diel investment in acoustic signalling and (ii) the temporal association between the diel variation in male signalling and female mate-searching behaviour. Overall food-supplemented males signalled more often, but the effect was only visible during the daytime. In the evening and the night, signal output was still high but the time spent signalling was unrelated to a male's nutritional condition. Females' mate-searching behaviour also showed a diel rhythm with peak activity during the afternoon, when differences among calling males were highest, and where signal output reliably reflects male quality. These findings suggest that males differing in nutritional condition may optimize their investment in signalling in relation to time of day as to maximize mating success.     

Applications of mass spectrometry in metabolomic studies of animal model and invertebrate systems

Metabolomics provides rich datasets for systems biology. Massspectrometric (MS) techniques are rapidly gaining in importancefor untargeted metabolic profiling. In this review, we surveythe various techniques for sample preparation and analysis relatingto the various MS techniques and illustrate the potential ofthese techniques for both observing complete metabolomes anddetecting changes in the metabolism resulting from genetic mutationof other perturbations. The use of some of these techniquesin the study of model organisms including rodent and variousinvertebrate models is described. The invertebrate systems areof particular interest since such organisms have valuable mutantresources, such as RNAi panels directed against nearly all thegenes in the genome. The demonstration that they are readilycompatible with metabolomic approaches is particularly importantfor systems approaches to metabolic pathways.      

Improvements in algal lipid production: a systems biology and gene editing approach

Background: In the wake of rising energy demands, microalgae have emerged as potential sources of sustainable and renewable carbon-neutral fuels, such as bio-hydrogen and bio-oil.

Purpose: For rational metabolic engineering, the elucidation of metabolic pathways in fine detail and their manipulation according to requirements is the key to exploiting the use of microalgae. Emergence of site-specific nucleases have revolutionized applied research leading to biotechnological gains. Genome engineering as well as modulation of the endogenous genome with high precision using CRISPR systems is being gradually employed in microalgal research. Further, to optimize and produce better algal platforms, use of systems biology network analysis and integration of omics data is required. This review discusses two important approaches: systems biology and gene editing strategies used on microalgal systems with a focus on biofuel production and sustainable solutions. It also emphasizes that the integration of such systems would contribute and compliment applied research on microalgae.

Conclusions: Recent advances in microalgae are discussed, including systems biology, gene editing approaches in lipid bio-synthesis, and antenna engineering. Lastly, it has been attempted here to showcase how CRISPR/Cas systems are a better editing tool than existing techniques that can be utilized for gene modulation and engineering during biofuel production.     

Species specificity and intraspecific variation in the chemical profiles of Heliconius butterflies across a large geographic range

In many animals, mate choice is important for the maintenance of reproductive isolation between species. Traits important for mate choice and behavioral isolation are predicted to be under strong stabilizing selection within species; however, such traits can also exhibit variation at the population level driven by neutral and adaptive evolutionary processes. Here, we describe patterns of divergence among androconial and genital chemical profiles at inter‐ and intraspecific levels in mimetic Heliconius butterflies. Most variation in chemical bouquets was found between species, but there were also quantitative differences at the population level. We found a strong correlation between interspecific chemical and genetic divergence, but this correlation varied in intraspecific comparisons. We identified “indicator” compounds characteristic of particular species that included compounds already known to elicit a behavioral response, suggesting an approach for identification of candidate compounds for future behavioral studies in novel systems. Overall, the strong signal of species identity suggests a role for these compounds in species recognition, but with additional potentially neutral variation at the population level.     

Lipopolysaccharide-stimulated responses in rat aortic endothelial cells by a systems biology approach

The vascular endothelium plays an important role in regulating immune and inflammatory responses to resist pathogens infection. Although it has been known that lipopolysaccharide (LPS) is a critical inducer of sepsis or endotoxemia, the systematic responses of LPS-stimulation in endothelial cells (ECs) are still unclear. The present study aims to analyze the late-phase responses of LPS-induced rat aortic ECs by using systematic biology approaches, including rat cDNA microarray, 2-DE and MALDI-TOF MS/MS, and cytokine protein array. Furthermore, to improve the efficiency of analysis of the bulk systematic data of rat, we designed a set of bioinformatic tools to convert and integrate these rat data into the corresponding human genes or proteins IDs based on BioCarta, KEGG, and Gene Ontology databases. Using the systematic analysis, it was shown that LPS could promote some signaling or metabolic pathways as well as pathophysiologic phenomena of proliferation, atherogenesis, inflammation, and apoptosis through activated nuclear factor-kappaB pathway in ECs. Interestingly, ECs also activated the mediators of anti-inflammation, antiapoptosis, and antioxidation to protect themselves. Moreover, the expressions of altered genes, proteins, and their involvement in the hypothetical signaling pathway can provide further understanding of inflammation associated responses in ECs.     

From computational modelling of the intrinsic apoptosis pathway to a systems-based analysis of chemotherapy resistance: achievements,perspectives and challenges in systems medicine

Our understanding of the mitochondrial or intrinsic apoptosis pathway and its role in chemotherapy resistance has increased significantly in recent years by a combination of experimental studies and mathematical modelling. This combined approach enhanced the quantitative and kinetic understanding of apoptosis signal transduction, but also provided new insights that systems-emanating functions (i.e., functions that cannot be attributed to individual network components but that are instead established by multi-component interplay) are crucial determinants of cell fate decisions. Among these features are molecular thresholds, cooperative protein functions, feedback loops and functional redundancies that provide systems robustness, and signalling topologies that allow ultrasensitivity or switch-like responses. The successful development of kinetic systems models that recapitulate biological signal transduction observed in living cells have now led to the first translational studies, which have exploited and validated such models in a clinical context. Bottom-up strategies that use pathway models in combination with higher-level modelling at the tissue, organ and whole body-level therefore carry great potential to eventually deliver a new generation of systems-based diagnostic tools that may contribute to the development of personalised and predictive medicine approaches. Here we review major achievements in the systems biology of intrinsic apoptosis signalling, discuss challenges for further model development, perspectives for higher-level integration of apoptosis models and finally discuss requirements for the development of systems medical solutions in the coming years.     

Wine biotechnology in South Africa: towards a systems approach to wine science

The wine industry in South Africa is over three centuries old and over the last decade has reemerged as a significant competitor in world wine markets. The Institute for Wine Biotechnology (IWBT) was established in partnership with the Department of Viticulture and Oenology at Stellenbosch University to foster basic fundamental research in the wine sciences leading to applications in the broader wine and grapevine industries. This review focuses on the different research programmes of the Institute (grapevine, yeast and bacteria biotechnology programmes, and chemical-analytical research), commercialisation activities (SunBio) and new initiatives to integrate the various research disciplines. An important focus of future research is the Wine Science Research Niche Area programme, which connects the different research thrusts of the IWBT and of several research partners in viticulture, oenology, food science and chemistry. This 'Functional Wine-omics' programme uses a systems biology approach to wine-related organisms. The data generated within the programme will be integrated with other data sets from viticulture, oenology, analytical chemistry and the sensory sciences through chemometrics and other statistical tools. The aim of the programme is to model aspects of the wine making process, from the vineyard to the finished product.