Genome, evolution, Drosophila and beyond: the new dimensions

A century ago a little fly with red eyes was first used for genetic studies. That insignificant fly, called at that time Drosophila ampelophila, revolutionized biology while becoming the model we know today under the name of Drosophila melanogaster. Since then its study has never ceased, but the field of interest has somewhat changed during the century. To caricature a little, today we essentially learn from Drosophila meetings that the fly has a brain! It is true that the fly is a tremendous model organism for neurobiology. But this fly is, in fact, an appropriate and recognized model for the whole of biology. Indeed, Drosophila meetings are exceptional opportunities to gather biologists of diverse backgrounds together. There we not only learn about the latest improvements in our field of interest, but surely appreciate learning another bit of biology. From this biological melting pot has emerged a culture very specific to the fly community. Thus besides neurobiology, cell biology and development, a diversity of other research fields exist; they all have their own place in the cultural and historical dimension of the "drosophila" model. Several communications from those diverse research fields were presented at the 8th Japanese Drosophila Research Conference (JDRC8) and are briefly covered here. We believe it more judicious to call the model "drosophila" without a capital initial, as the model has never really been limited to only the Drosophila genus. The vernacular name "drosophila" is currently used to designate any fly of the Drosophilidae family and we believe the term more appropriate than "small fruit fly" or "vinegar fly" to better include the species and ecological diversity of the model.     

Drosophila as a lipotoxicity model organism — more than a promise?

Looking back over the century long research career of the fruit fly, Drosophila melanogaster has frequently been in the scientific spotlight with respect to fundamental discoveries in biology. The last decade witnessed the increasing importance of the fly as a human disease model but studies on energy homeostasis and lipometabolism remain in their infancy. This perspective, addressing readers largely unfamiliar with the Drosophila model system, aims to highlight the starting points for which the fly could be employed to gain a deeper understanding of lipotoxicity and possibly contribute to strategies for the identification of novel drug targets relevant to type 2 diabetes mellitus and the metabolic syndrome.     

Fruit fly research in China

Served as a model organism over a century, fruit fly has significantly pushed forward the development of global scientific research, including in China. The high similarity in genomic features between fruit fly and human enables this tiny insect to benefit the biomedical studies of human diseases. In the past decades, Chinese biologists have used fruit fly to make numerous achievements on understanding the fundamental questions in many diverse areas of biology. Here, we review some of the recent fruit fly studies in China, and mainly focus on those studies in the fields of stem cell biology, cancer therapy and regeneration medicine, neurological disorders and epigenetics.     

High-resolution, in vivo magnetic resonance imaging of Drosophila at 18.8 Tesla

High resolution MRI of live Drosophila was performed at 18.8 Tesla, with a field of view less than 5 mm, and administration of manganese or gadolinium-based contrast agents. This study demonstrates the feasibility of MR methods for imaging the fruit fly Drosophila with an NMR spectrometer, at a resolution relevant for undertaking future studies of the Drosophila brain and other organs. The fruit fly has long been a principal model organism for elucidating biology and disease, but without capabilities like those of MRI. This feasibility marks progress toward the development of new in vivo research approaches in Drosophila without the requirement for light transparency or destructive assays.     

The contribution of the Drosophila model to lipid droplet research

Intracellular lipid droplets have long been misconceived as evolutionarily conserved but functionally frugal components of cellular metabolism. An ever-growing repertoire of functions has elevated lipid droplets to fully-fledged cellular organelles. Insights into the multifariousness of these organelles have been obtained from a range of model systems now employed for lipid droplet research including the fruit fly, Drosophila melanogaster. This review summarizes the progress in fly lipid droplet research along four main avenues: the role of lipid droplets in fat storage homeostasis, the control of lipid droplet structure, the lipid droplet surface as a dynamic protein-association platform, and lipid droplets as mobile organelles. Moreover, the research potential of the fruit fly model is discussed with respect to the prevailing general questions in lipid droplet biology.     

Michael Akam and the rise of evolutionary developmental biology

Michael Akam has been awarded the 2007 Kowalevsky medal for his many research accomplishments in the area of evolutionary developmental biology. We highlight three tributaries of Michael’s contribution to evolutionary developmental biology. First, he has made major contributions to our understanding of development of the fruit fly, Drosophila melanogaster. Second, he has maintained a consistent focus on several key problems in evolutionary developmental biology, including the evolving role of Hox genes in arthropods and, more recently, the evolution of segmentation mechanisms. Third, Michael has written a series of influential reviews that have integrated progress in developmental biology into an evolutionary perspective. Michael has also made a large impact on the field through his effective mentorship style, his selfless promotion of younger colleagues, and his leadership of the University Museum of Zoology at Cambridge and the European community of evolutionary developmental biologist.     

Saprophagous insect larvae,Drosophila melanogaster,profit from increased species richness in beneficial microbes

Female fruit flies, Drosophila melanogaster, lay their eggs on decaying plant material. Foraging fly larvae strongly depend on the availability of dietary microbes, such as yeasts, to reach the adult stage. In contrast, strong interference competition with filamentous fungi can cause high mortality among Drosophila larvae. Given that many insects are known for employing beneficial microbes to combat antagonistic ones, we hypothesized that fly larvae engaged in competition with the noxious mould Aspergillus nidulans benefit from the presence of dietary yeast species, especially when they are associated with increasingly species rich yeast communities (ranging from one to six yeast species per community). On a nutrient‐limited fruit substrate infested with A. nidulans, both larval survival and development time were positively affected by more diverse yeast communities. On a mould‐free fruit substrate, merely larval development but not survival was found to be affected by increasing species richness of dietary yeasts. Not only yeast diversity had an effect on D. melanogaster life‐history traits, but also the identity of the yeast combinations. These findings demonstrate the importance of the structure and diversity of microbial communities in mutualistic animal–microbe interactions.     

Drosophila as a screening tool to study human neurodegenerative diseases

In an aging society, research involving neurodegenerative disorders is of paramount importance. Over the past few years, research on Alzheimer's and Parkinson's diseases has made tremendous progress. Experimental studies, however, rely mostly on transgenic animal models, preferentially using mice. Although experiments on mice have enormous advantages, they also have some inherent limitations, some of which can be overcome by the use of Drosophila melanogaster as an experimental animal. Among the major advantages of using the fly is its small genome, which can also be modified very easily. The fact that its genome lends itself to diverse alterations (e. g. mutagenesis, transposons) has made the fly a useful organism to perform large‐scale and genome‐wide screening approaches. This has opened up an entirely new field of experimental research aiming to elucidate genetic interactions and screen for modifiers of disease processes in vivo. Here, we provide a brief overview of how flies can be used to analyze molecular mechanisms underlying human neurodegenerative diseases.     

Eye development at the Houston "Fly Meeting"

The 47th Annual Drosophila Research Conference or "Fly Meeting" took place at Houston, Texas, USA from March 29th- April 2nd, 2006, under the aegis of the Genetics Society of America. The Fly Meeting provides an excellent opportunity for fly researchers to present their work and to get a snapshot of recent developments and upcoming trends in their research field. The fruit fly, Drosophila melanogaster is a very versatile model to study growth, patterning, neural development, evolution, systemetics and various other facets of biomedical science. The topics presented in the meeting covered a very broad spectrum of fly research. In this commentary, I have focused mainly on the presentations related to two fields: 1) research in various fields that use the Drosophila eye as a model system, and 2) the community resources available to all fly researchers.     

The power of Drosophila in modeling human disease mechanisms

Six years ago, DMM launched a subject collection called ‘Drosophila as a Disease Model’. This collection features Review-type articles and original research that highlight the power of Drosophila research in many aspects of human disease modeling. In the ensuing years, Drosophila research has further expanded to capitalize on genome editing, development of resources, and further interest in studying rare disease mechanisms. In the current issue of DMM, we again highlight the versatility, breadth, and scope of Drosophila research in human disease modeling and translational medicine. While many researchers have embraced the power of the fly, many more could still be encouraged to appreciate the strengths of Drosophila and how such research can integrate across species in a multi-pronged approach. Only when we truly acknowledge that all models contribute to our understanding of human biology, can we take advantage of the scope of current research endeavors.

Summary: This Editorial encourages us to embrace the power of the fly in studying human disease and highlights how Drosophila studies can be integrated with research in other species to further our understanding of human biology.

For over a century, scientists have used the fruit fly to learn about fundamental and evolutionarily conserved genetic and cellular processes. The pioneering work of Thomas Hunt Morgan and his students, in the early 20th century, proved that genes are located on chromosomes and led to the first chromosome linkage maps (Morgan, 1910). In the 1980s, Ed Lewis, Christiane Nüsslein-Volhard and Eric Wieschaus showed that individual genes could be mutated to cause characteristic embryonic patterning defects (Lewis, 1978; Nüsslein-Vollhard and Wieschaus, 1980). Their genetic studies allowed them to order genes within functional pathways through epistasis analyses. The genes they identified have counterparts across species and play key roles in development and disease from flies to humans. Indeed, much of the molecular circuitry for key signaling pathways, such as RAS, Notch, Hedgehog and Wnt, was elucidated in Drosophila (Ashton-Beaucage and Therrien, 2017; Bejsovec, 2018; Ingham, 2018; Salazar and Yamamoto, 2018). This rich history has established Drosophila as a powerful tool in biology, paving the way for further advances in basic and translational research.     

<Emphasis Type="Italic">Drosophila</Emphasis> as models to understand the adaptive process during invasion

The last few decades have seen a growing number of species invasions globally, including many insect species. In drosophilids, there are several examples of successful invasions, i.e. Zaprionus indianus and Drosophila subobscura some decades ago, but the most recent and prominent example is the invasion of Europe and North America by the pest species, Drosophila suzukii. During the invasive process, species often encounter diverse environmental conditions that they must respond to, either through rapid genetic adaptive shifts or phenotypic plasticity, or by some combination of both. Consequently, invasive species constitute powerful models for investigating various questions related to the adaptive processes that underpin successful invasions. In this paper, we highlight how Drosophila have been and remain a valuable model group for understanding these underlying adaptive processes, and how they enable insight into key questions in invasion biology, including how quickly adaptive responses can occur when species are faced with new environmental conditions.     

Drosophila melanogaster as a model system for the study of the function of calcium/calmodulin-dependent protein kinase II in synaptic plasticity

Drosophila melanogaster has been used as a biological model system for almost a century. In the last several decades,Drosophila has been used as a system to probe the molecular basis of behavior and discoveries in the fly have been at the forefront of the elucidation of important basic mechanisms. This review will outline the variety of approaches that makeDrosophila an excellent model system with which to study the function of the enzyme calcium/calmodulin-dependent protein kinase II (CaMKII) in synaptic plasticity. CaMKII has a well documented role in behavior and synaptic plasticity in both vertebrates and invertebrates. The behavioral and genetic richness ofDrosophila allow for a multi-level approach to understanding the physiological roles of this enzyme's function.     

The biology of the phonotactic parasitoid, Homotrixa sp. (Diptera: Tachinidae), and its impact on the survival of male Sciarasaga quadrata (Orthoptera: Tettigoniidae) in the field

Abstract.

• 1 Unlike most parasitoids, tachinid flies of the tribe Ormiini use sound to locate their hosts. Although thought to exert selection pressure on their host's calling behaviour, little is known about the biology of ormiines. Accordingly, this study reports the biology and impact of the ormiine Hornotrixa sp. upon calling males of the univoltine bushcricket Sciarasaga quadrata Rentz in south-western Australia.
• 2 Populations of adult S.quadrata were monitored in the field over two successive calling seasons. Females, which do not call, were not parasitized by Hornotrixa sp., but the risk of parasitism for males increased as the 3-month calling season progressed. Parasitism did not commence until c. 2 weeks into the calling season, but by the end of the season up to 87% of surviving males were parasitized.
• 3 Parasitized males lived for 14 days and were found singing until their penultimate evening before death in the field. Unparasitized males lived on average 69 days and a maximum of 119 days.
• 4 Multiparasitism of hosts was common, with up to sixteen fly larvae found within parasitized males. The number of fly larvae within hosts significantly increased at the end of the season. However, successful emergence of fly larvae from hosts, as well as pupal size, significantly decreased as more than one fly larva developed within the host.
• 5 Hornotrixa sp. has a long pupal duration of 30–31 days at 20°C. As a consequence, only one complete fly generation, which overwinters in the pupal stage, is likely within each host generation.
• 6 No evidence for differential (size-bias) mortality by Hornotrixa sp. on male S.quadrata was found. The size of parasitized and unparasitized males collected in the field was not significantly different.
• 7 It is concluded that Hornotrixa sp. is a significant mortality factor acting on the survival of adult male S.quadrata.

     

Drosophila melanogaster as an emerging model host for entomopathogenic fungi

Entomopathogenic fungi (EPF) infect insects and are of interest for understanding host-pathogen interactions and biological control of insect pests. The fruit fly Drosophila melanogaster offers an excellent model system for exploring the biology of EPF and their interactions with insects. In this review, we describe the advantages of using D. melanogaster as a model system to study EPF and highlight EPF of relevance to agriculture. We also propose possible directions for future research in this area. We predict that in the future, D. melanogaster will continue to be a productive system for understanding the biology of the fungi attacking insects and will no doubt contribute to the future of biological control, conservation and other areas.     

Recent findings in evolution and function of insect innexins

The past decade has seen significant advances in the field of innexin biology, particularly in the model invertebrate organisms, the nematode Caenorhabditis elegans and the fly Drosophila melanogaster. However, advances in genomics and functional techniques during this same period are ushering in a period of comparative innexin biology. Insects are the most diverse metazoan taxa in terms of species number, as well as in developmental, physiological, and morphological processes. Combined with genomics data, the study of innexins should rapidly advance. In this review, we consider the current state of knowledge regarding innexins in insects, focusing on innexin diversity, both evolutionary and functional. We also consider an unusual set of innexins, known as vinnexins, that have been isolated from mutualistic viruses of some parasitoid wasps. We conclude with a call to study insect innexins from a broader, evolutionary perspective. Knowledge derived from such comparative studies will offer significant insight into developmental and evolutionary physiology, as well as specific functional processes in a taxon that has huge biomedical and ecological impact on humans.     

Casein kinase 2, circadian clocks, and the flight from mutagenic light

Circadian clocks play a fundamental role in biology and disease. Much has been learned about the molecular underpinnings of these biological clocks from genetic studies in model organisms, such as the fruit fly, Drosophila melanogaster. Here we review the literature from our lab and others that establish a role for the protein kinase CK2 in Drosophila clock timing. Among the clock genes described thus far, CK2 is unique in its involvement in plant, fungal, as well as animal circadian clocks. We propose that this reflects an ancient, conserved function for CK2 in circadian clocks. CK2 and other clock genes have been implicated in cellular responses to DNA damage, particularly those induced by ultraviolet (UV) light. The finding of a dual function of CK2 in clocks and in UV responses supports the notion that clocks evolved to assist organisms in avoiding the mutagenic effects of daily sunlight.     

Coexistence of drosophilid flies: Aggregation, patch size diversity and parasitism

We carried out field experiments to investigate the coexistence of Drosophila species in domestic and forest areas on the basis of the aggregation model. Three cosmopolitan species Drosophila simulans Sturtevant, Drosophila melanogaster Meigen and Drosophila immigrans Sturtevant, and a native species, Drosophila auraria Peng, emerged abundantly from banana placed at the domestic station, while Drosophila immigrans and five native species, Drosophila lutescens Okada, Drosophila rufa Kikkawa and Peng, Drosophila bizonata Kikkawa and Peng, Drosophila sternopleuralis Okada and Kurokawa and Scaptodrosophila coracina (Kikkawa and Peng), were abundant at the forest station. The present analysis suggests that their coexistence was facilitated by the aggregation mechanism. In the cosmopolitan species, the density of individuals that emerged from patches increased with the increase of patch size, but the relationship between fly density and patch size was not clear in the native species. This difference in distribution patterns between the cosmopolitan and native species is likely to be due to the difference in the female visiting behavior. In the present analysis, however, it was not clear whether patch size diversity facilitated their coexistence or not. The effect of patch size diversity may have been masked, because the effect of aggregation was more prominent. The rate of parasitism by wasps was high in October at the domestic station, and in May and June at the forest station. The present result suggests that the rate of parasitism was density-dependent, at least at the domestic station, and therefore parasitism facilitates the coexistence of drosophilid species in domestic areas.     

Ultrastructural comparison of the Drosophila larval and adult ventral abdominal neuromuscular junction

Drosophila melanogaster has recently emerged as model system for studying synaptic transmission and plasticity during adulthood, aging and neurodegeneration. However, still little is known about the basic neuronal mechanisms of synaptic function in the adult fly. Per se , adult Drosophila neuromuscular junctions should be highly suited for studying these aspects as they allow for genetic manipulations in combination with ultrastructural and electrophysiological analyses. Although different neuromuscular junctions of the adult fly have been described during the last years, a direct ultrastructural comparison with their larval counterpart is lacking. The present study was designed to close this gap by providing a detailed ultrastructural comparison of the larval and the adult neuromuscular junction of the ventrolongitudinal muscle. Assessment of several parameters revealed similarities but also major differences in the ultrastructural organisation of the two model neuromuscular junctions. While basic morphological parameters are retained from the larval into the adult stage, the analysis discovered major differences of potential functional relevance in the adult: The electron‐dense membrane apposition of the presynaptic and postsynaptic membrane is shorter, the subsynaptic reticulum is less elaborated and the number of synaptic vesicles at a certain distance of the presynaptic membrane is higher.     

Progress inDrosophila genome manipulation

The introduction of cloned and manipulated genetic material into the germline of an experimental organism is one of the most powerful tools of modern biology. In the case of the fruit fly,Drosophila melanogaster, there is also an unparalleled range of sophisticated genetic tools to facilitate subsequent analysis. In consequence,Drosophila remains a most favourable model organism for the dissection of gene structure and functionin vivo. In this review we look at some of the achievements to date inDrosophila genome manipulation, and at what may be possible in the near future.