Drosophila in bio–medical science
Drosophila melanogaster (Diptera: Drosophilidae) is a small fly, about 3mm long, commonly known as the fruit fly. They are cosmopolitan, human commensal, which originated in sub-Saharan Africa and today inhabit all continents except Antarctica. In nature, associated primarily with rotting fruits where they feed on yeast, bacteria, and plant matter within ripe. Fruit flies are generalists and use a variety of fruits and vegetables for nutrition, life and reproduction.
Ever since T. H. Morgan, in the early 1900s, began his research using Drosophila as a model organism, this little fly has gained an important place in research on fundamental animal biology. Apart from research in the field of genetics and behaviour, this fly has an important place in research related to genomics, development, physiology, ecology, and evolution, but also in biomedical research. Over the years, this fly has been responsible for even 6 Nobel Prizes in Physiology or Medicine:
- T. H. Morgan discovered the relationship of genes to chromosomes and the role played by chromosomes in heredity (1933);
- H. J. Muller for discovering that radiation increase mutation rates (1946);
- E. Lewis, C. Nüsslein-Volhard, and E. Wieschaus for discovering genetic control of embryonic development and cellular pathways (1995);
- R. Axel and L. B. Buck for discoveries of “odorant receptors and the organization of the olfactory system” (2004);
- B. A. Beutler and J. A. Hoffmann for discoveries concerning the activation of innate immunity (2011);
- J. C. Hall, M. Rosbash and M. W. Young for discoveries of the molecular mechanisms that control circadian rhythms (2017).
What makes D. melanogaster such good models?
- They are small and easy to manipulate;
- Flies are easily cultured in the laboratory and have many offspring and brief generation times: D. melanogaster is holometabolous with a short generation time: from a fertilized egg to an adult in 10 to 12 days at 25°. After fertilization, the embryo develops and hatches into a worm-like larva in one day, followed by three larval stages. The first and second instars last about one day each, while the third instar requires two days. Thus, larval development is complete in five days, after which they pupate. They remain in the stadium of immobile pupa for about five days. Due to that period, the body is completely remodelled to give the adult winged form. Adults emerge from the pupal case and became fertile within about 12 hours;
- It is easy to differentiate the sexes: adults have pronounced sexual dimorphism;
- They have a simple genome and completely sequencing: fruit flies have 4 pairs of chromosomes (one is the sex chromosomes, and three are autosomes), about 14000 protein-coding genes. Genome is compact and easy to manipulate;
- Care and culture flies require little space and equipment, it is low in cost.
In the past years, D. melanogaster is a valuable model in the creation of animal models of human disease. It is known that about 60% of human genes and 75% of human disease genes have homologs in D. melanogaster. The fruit fly is increasingly used in biomedical research, especially when it comes to complex disorders, like mental or neurological illness, heart disease, obesity, and cancer. Drosophila has an important place in research related to Alzheimer’s disease, autism spectrum disorders, Fragile X syndrome, spinocerebellar ataxia type 1 (SCA1), Huntington’s disease, Parkinson’s disease (PD), epileptic encephalopathy, phosphoribosyl pyrophosphate synthetase (PRPS)-associated disorders, the transcription and nucleotide excision repair factor TFIIH-related diseases, central nervous system disorders associated with glial defects, multi sex combs (mxc)-associated lymphoma, alcohol use disorder, maturity-onset diabetes of the young type 2 (MODY-2), amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease (CMT) and infectious diseases.
Loss-of-function alleles have been identified for near to 60% of genes, of which 77% are orthologs to human genes. Mutations were most often induced by chemicals and radiation. In recent years, transgenic technology has expanded the experimental range of use of Drosophila, allowing human genes to be introduced into flies. On the one hand, this allowed us to obtain information about how human gene products, mostly proteins, can contribute to the improvement of the mutant phenotype of flies, on the other hand, the expression of human disease alleles in flies often mimics disease pathology. This is possible due to the high evolutionary conservation of genetic and cellular signalling pathways in flies and humans.