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Polycomb-group proteins

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Polycomb-group proteins ( PcG proteins ) are a family of protein complexes first discovered in fruit flies that can remodel chromatin such that epigenetic silencing of genes takes place. Polycomb-group proteins are well known for silencing Hox genes through modulation of chromatin structure during embryonic development in fruit flies ( Drosophila melanogaster ). They derive their name from the fact that the first sign of a decrease in PcG function is often a homeotic transformation of posterior legs towards anterior legs, which have a characteristic comb-like set of bristles.

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106-894: In Drosophila , the Trithorax-group (trxG) and Polycomb-group (PcG) proteins act antagonistically and interact with chromosomal elements, termed Cellular Memory Modules (CMMs). Trithorax-group (trxG) proteins maintain the active state of gene expression while the Polycomb-group (PcG) proteins counteract this activation with a repressive function that is stable over many cell generations and can only be overcome by germline differentiation processes. Polycomb Gene complexes or PcG silencing consist of at least three kinds of multiprotein complex Polycomb Repressive Complex 1 (PRC1), PRC2 and PhoRC . These complexes work together to carry out their repressive effect. PcGs proteins are evolutionarily conserved and exist in at least two separate protein complexes;

212-681: A white eyed mutant in 1910 to the academic community. He was in search of a model organism to study genetic heredity and required a species that could randomly acquire genetic mutation that would visibly manifest as morphological changes in the adult animal. His work on Drosophila earned him the 1933 Nobel Prize in Medicine for identifying chromosomes as the vector of inheritance for genes. This and other Drosophila species are widely used in studies of genetics , embryogenesis , chronobiology , speciation , neurobiology , and other areas. However, some species of Drosophila are difficult to culture in

318-460: A 2014 study from McGill University in Montreal, Canada which suggests that mice handled by men rather than women showed higher stress levels. Another study in 2016 suggested that gut microbiomes in mice may have an impact upon scientific research. Ethical concerns, as well as the cost, maintenance and relative inefficiency of animal research has encouraged development of alternative methods for

424-573: A high pectin concentration, which is an indicator of how much alcohol will be produced during fermentation. Citrus, morinda , apples, pears, plums, and apricots belong into this category. The larvae of at least one species, D. suzukii , can also feed in fresh fruit and can sometimes be a pest. A few species have switched to being parasites or predators . Many species can be attracted to baits of fermented bananas or mushrooms, but others are not attracted to any kind of baits. Males may congregate at patches of suitable breeding substrate to compete for

530-580: A local review board called the Institutional Animal Care and Use Committee (IACUC). All laboratory experiments involving living animals are reviewed and approved by this committee. In addition to proving the potential for benefit to human health, minimization of pain and distress, and timely and humane euthanasia, experimenters must justify their protocols based on the principles of Replacement, Reduction and Refinement. "Replacement" refers to efforts to engage alternatives to animal use. This includes

636-406: A lower total neutrophil fraction in the blood , a lower neutrophil enzymatic capacity, lower activity of the complement system , and a different set of pentraxins involved in the inflammatory process ; and lack genes for important components of the immune system, such as IL-8 , IL-37 , TLR10 , ICAM-3 , etc. Laboratory mice reared in specific-pathogen-free (SPF) conditions usually have

742-473: A matter of putting in a small piece of the natural host to receive the eggs. The Drosophila Species Stock Center located at Cornell University in Ithaca , New York, maintains cultures of hundreds of species for researchers. Drosophila is considered one of the most valuable genetic model organisms; both adults and embryos are experimental models. Drosophila is a prime candidate for genetic research because

848-547: A model for neuronal development by Sydney Brenner in 1963, and has been extensively used in many different contexts since then. C. elegans was the first multicellular organism whose genome was completely sequenced, and as of 2012, the only organism to have its connectome (neuronal "wiring diagram") completed. Arabidopsis thaliana is currently the most popular model plant. Its small stature and short generation time facilitates rapid genetic studies, and many phenotypic and biochemical mutants have been mapped. A. thaliana

954-666: A nearly transparent body during early development, which provides unique visual access to the animal's internal anatomy during this time period. Zebrafish are used to study development, toxicology and toxicopathology, specific gene function and roles of signaling pathways. Other important model organisms and some of their uses include: T4 phage (viral infection), Tetrahymena thermophila (intracellular processes), maize ( transposons ), hydras ( regeneration and morphogenesis ), cats (neurophysiology), chickens (development), dogs (respiratory and cardiovascular systems), Nothobranchius furzeri (aging), non-human primates such as

1060-551: A portal from which to download sequences (DNA, RNA, or protein) or to access functional information on specific genes, for example the sub-cellular localization of the gene product or its physiological role. Many animal models serving as test subjects in biomedical research, such as rats and mice, may be selectively sedentary , obese and glucose intolerant . This may confound their use to model human metabolic processes and diseases as these can be affected by dietary energy intake and exercise . Similarly, there are differences between

1166-585: A rather immature immune system with a deficit of memory T cells . These mice may have limited diversity of the microbiota , which directly affects the immune system and the development of pathological conditions. Moreover, persistent virus infections (for example, herpesviruses ) are activated in humans, but not in SPF mice, with septic complications and may change the resistance to bacterial coinfections . “Dirty” mice are possibly better suitable for mimicking human pathologies. In addition, inbred mouse strains are used in

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1272-419: A time, so that they can be laid together on one site. Others that breed in more-abundant but less nutritious substrates, such as leaves, may only lay one egg per day. The eggs have one or more respiratory filaments near the anterior end; the tips of these extend above the surface and allow oxygen to reach the embryo. Larvae feed not on the vegetable matter itself, but on the yeasts and microorganisms present on

1378-468: A unicellular green alga with well-studied genetics, is used to study photosynthesis and motility . C. reinhardtii has many known and mapped mutants and expressed sequence tags, and there are advanced methods for genetic transformation and selection of genes. Dictyostelium discoideum is used in molecular biology and genetics , and is studied as an example of cell communication , differentiation , and programmed cell death . Among invertebrates,

1484-503: A wide variety of experimental techniques and goals from many different levels of biology—from ecology , behavior and biomechanics , down to the tiny functional scale of individual tissues , organelles and proteins . Inquiries about the DNA of organisms are classed as genetic models (with short generation times, such as the fruitfly and nematode worm), experimental models, and genomic parsimony models, investigating pivotal position in

1590-548: A wider assortment of lineages on the tree of life . The primary reason for the use of model organisms in research is the evolutionary principle that all organisms share some degree of relatedness and genetic similarity due to common ancestry . The study of taxonomic human relatives, then, can provide a great deal of information about mechanism and disease within the human body that can be useful in medicine. Various phylogenetic trees for vertebrates have been constructed using comparative proteomics , genetics, genomics as well as

1696-412: Is Escherichia coli ( E. coli ), which has been intensively investigated for over 60 years. It is a common, gram-negative gut bacterium which can be grown and cultured easily and inexpensively in a laboratory setting. It is the most widely used organism in molecular genetics , and is an important species in the fields of biotechnology and microbiology , where it has served as the host organism for

1802-593: Is a genus of fly , belonging to the family Drosophilidae , whose members are often called "small fruit flies" or pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit. They should not be confused with the Tephritidae , a related family, which are also called fruit flies (sometimes referred to as "true fruit flies"); tephritids feed primarily on unripe or ripe fruit , with many species being regarded as destructive agricultural pests, especially

1908-441: Is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Model organisms are widely used to research human disease when human experimentation would be unfeasible or unethical . This strategy is made possible by the common descent of all living organisms, and

2014-492: Is a connection between the number of time females choose to mate and chromosomal variants of the third chromosome. It is believed that the presence of the inverted polymorphism is why re-mating by females occurs. The stability of these polymorphisms may be related to the sex-ratio meiotic drive. However, for Drosophila subobscura , the main mating system is monandry, not normally seen in Drosophila. The following section

2120-438: Is an attractive behaviour. Females respond via their perception of the behavior portrayed by the male. Male and female Drosophila use a variety of sensory cues to initiate and assess courtship readiness of a potential mate. The cues include the following behaviours: positioning, pheromone secretion, following females, making tapping sounds with legs, singing, wing spreading, creating wing vibrations, genitalia licking, bending

2226-417: Is based on the following Drosophila species: Drosophila serrata , Drosophila pseudoobscura , Drosophila melanogaster , and Drosophila neotestacea . Polyandry is a prominent mating system among Drosophila . Females mating with multiple sex partners has been a beneficial mating strategy for Drosophila . The benefits include both pre and post copulatory mating. Pre-copulatory strategies are

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2332-494: Is based on the following Drosophila species: Drosophila melanogaster , Drosophila simulans , and Drosophila mauritiana . Sperm competition is a process that polyandrous Drosophila females use to increase the fitness of their offspring. The female Drosophila has two sperm storage organs, the spermathecae and seminal receptacle, that allows her to choose the sperm that will be used to inseminate her eggs. However, some species of Drosophila have evolved to only use one or

2438-439: Is difficult to build an animal model that perfectly reproduces the symptoms of depression in patients. Depression, as other mental disorders , consists of endophenotypes that can be reproduced independently and evaluated in animals. An ideal animal model offers an opportunity to understand molecular , genetic and epigenetic factors that may lead to depression. By using animal models, the underlying molecular alterations and

2544-407: Is explored as a mechanism of controlling viral diseases ( e.g. Dengue fever) by transferring these Wolbachia to disease-vector mosquitoes. The S. poulsonii strain of Drosophila neotestacea protects its host from parasitic wasps and nematodes using toxins that preferentially attack the parasites instead of the host. Since the Drosophila species is one of the most used model organisms, it

2650-502: Is inactivated in the young embryo . The Polycomb gene FIE is expressed in unfertilised egg cells of the moss Physcomitrella patens and expression ceases after fertilisation in the developing diploid sporophyte. It has been shown that unlike in mammals the PcG are necessary to keep the cells in a differentiated state. Consequently, loss of PcG causes de-differentiation and promotes embryonic development. Polycomb-group proteins also intervene in

2756-450: Is known to regulate ink4 locus (p16, p19). Regulation of Polycomb-group proteins at bivalent chromatin sites is performed by SWI/SNF complexes, which oppose the accumulation of Polycomb complexes through ATP-dependent eviction. In Physcomitrella patens the PcG protein FIE is specifically expressed in stem cells such as the unfertilized egg cell . Soon after fertilisation the FIE gene

2862-632: Is no substitute for a living organism when studying complex interactions in disease pathology or treatments. Debate about the ethical use of animals in research dates at least as far back as 1822 when the British Parliament under pressure from British and Indian intellectuals enacted the first law for animal protection preventing cruelty to cattle. This was followed by the Cruelty to Animals Act of 1835 and 1849, which criminalized ill-treating, over-driving, and torturing animals. In 1876, under pressure from

2968-431: Is no useful in vitro model system available. Model organisms are drawn from all three domains of life, as well as viruses . One of the first model systems for molecular biology was the bacterium Escherichia coli ( E. coli ), a common constituent of the human digestive system. The mouse ( Mus musculus ) has been used extensively as a model organism and is associated with many important biological discoveries of

3074-575: Is one step in the immune responses to some pathogens. Dudzic et al. 2019 additionally find a large number of shared serine protease messengers between Spätzle/Toll and melanization and a large amount of crosstalk between these pathways.   immigrans-tripunctata  radiation   D. quadrilineata  species group   Samoaia   Zaprionus   D. tumiditarsus  species group   Liodrosophila   Dichaetophora   Hirtodrosophila Model organism A model organism

3180-420: Is particularly useful as a toxicology model, and as a neurological model and source of primary cell cultures, owing to the larger size of organs and suborganellar structures relative to the mouse, while eggs and embryos from Xenopus tropicalis and Xenopus laevis (African clawed frog) are used in developmental biology, cell biology, toxicology, and neuroscience. Likewise, the zebrafish ( Danio rerio ) has

3286-705: Is seen during courtship and mating . Drosophila species are prey for many generalist predators, such as robber flies . In Hawaii , the introduction of yellowjackets from mainland United States has led to the decline of many of the larger species. The larvae are preyed on by other fly larvae, staphylinid beetles , and ants . Fruit flies use several fast-acting neurotransmitters, similar to those found in humans, which allow neurons to communicate and coordinate behavior. Acetylcholine, glutamate, gamma-aminobutyric acid (GABA), dopamine, serotonin, and histamine are all neurotransmitters that can be found in humans, but Drosophila also have another neurotransmitter, octopamine,

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3392-479: Is similar to a human condition. These test conditions are often termed as animal models of disease . The use of animal models allows researchers to investigate disease states in ways which would be inaccessible in a human patient, performing procedures on the non-human animal that imply a level of harm that would not be considered ethical to inflict on a human. The best models of disease are similar in etiology (mechanism of cause) and phenotype (signs and symptoms) to

3498-496: Is studied, again, because it is easy to grow for an animal, has various visible congenital traits and has a polytene (giant) chromosome in its salivary glands that can be examined under a light microscope. The roundworm Caenorhabditis elegans is studied because it has very defined development patterns involving fixed numbers of cells, and it can be rapidly assayed for abnormalities. Animal models serving in research may have an existing, inbred or induced disease or injury that

3604-477: Is used with the aim of solving medical problems such as Alzheimer's disease, AIDS, multiple sclerosis, spinal cord injury, many headaches, and other conditions in which there is no useful in vitro model system available. Models are those organisms with a wealth of biological data that make them attractive to study as examples for other species and/or natural phenomena that are more difficult to study directly. Continual research on these organisms focuses on

3710-407: Is very diverse in appearance, behavior, and breeding habitat. The term " Drosophila ", meaning "dew-loving", is a modern scientific Latin adaptation from Greek words δρόσος , drósos , " dew ", and φιλία , philía , "lover". Drosophila species are small flies, typically pale yellow to reddish brown to black, with red eyes. When the eyes (essentially a film of lenses) are removed,

3816-497: The D. melanogaster Spiroplasma poulsonii (named MSRO). The male-killing factor of the D. melanogaster MSRO strain was discovered in 2018, solving a decades-old mystery of the cause of male-killing. This represents the first bacterial factor that affects eukaryotic cells in a sex-specific fashion, and is the first mechanism identified for male-killing phenotypes. Alternatively, they may protect theirs hosts from infection. Drosophila Wolbachia can reduce viral loads upon infection, and

3922-598: The Drosophila DNA damage response, including deficiencies in expression of genes involved in DNA damage repair , accelerates intestinal stem cell ( enterocyte ) aging. Sharpless and Depinho reviewed evidence that stem cells undergo intrinsic aging and speculated that stem cells grow old, in part, as a result of DNA damage. The following section is based on the following Drosophila species: Drosophila simulans and Drosophila melanogaster . Courtship behavior of male Drosophila

4028-458: The Mediterranean fruit fly . One species of Drosophila in particular, Drosophila melanogaster , has been heavily used in research in genetics and is a common model organism in developmental biology . The terms "fruit fly" and " Drosophila " are often used synonymously with D. melanogaster in modern biological literature. The entire genus, however, contains more than 1,500 species and

4134-502: The National Anti-Vivisection Society , the Cruelty to Animals Act was amended to include regulations governing the use of animals in research. This new act stipulated that 1) experiments must be proven absolutely necessary for instruction, or to save or prolong human life; 2) animals must be properly anesthetized; and 3) animals must be killed as soon as the experiment is over. Today, these three principles are central to

4240-494: The fru mutation leads back to the typical courtship behavior. A novel class of pheromones was found to be conserved across the subgenus Drosophila in 11 desert dwelling species. These pheromones are triacylglycerides that are secreted exclusively by males from their ejaculatory bulb and transferred to females during mating. The function of the pheromones is to make the females unattractive to subsequent suitors and thus inhibit courtship by other males. The following section

4346-410: The fruit fly Drosophila melanogaster is famous as the subject of genetics experiments by Thomas Hunt Morgan and others. They are easily raised in the lab, with rapid generations, high fecundity , few chromosomes , and easily induced observable mutations. The nematode Caenorhabditis elegans is used for understanding the genetic control of development and physiology. It was first proposed as

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4452-622: The rhesus macaque and chimpanzee ( hepatitis , HIV , Parkinson's disease , cognition , and vaccines ), and ferrets ( SARS-CoV-2 ) The organisms below have become model organisms because they facilitate the study of certain characters or because of their genetic accessibility. For example, E. coli was one of the first organisms for which genetic techniques such as transformation or genetic manipulation has been developed. The genomes of all model species have been sequenced , including their mitochondrial / chloroplast genomes. Model organism databases exist to provide researchers with

4558-558: The 20th and 21st centuries. Other examples include baker's yeast ( Saccharomyces cerevisiae ), the T4 phage virus, the fruit fly Drosophila melanogaster , the flowering plant Arabidopsis thaliana , and guinea pigs ( Cavia porcellus ). Several of the bacterial viruses ( bacteriophage ) that infect E. coli also have been very useful for the study of gene structure and gene regulation (e.g. phages Lambda and T4 ). Disease models are divided into three categories: homologous animals have

4664-546: The DBA ("dilute, brown and non-agouti") inbred mouse strain and the systematic generation of other inbred strains. The mouse has since been used extensively as a model organism and is associated with many important biological discoveries of the 20th and 21st centuries. In the late 19th century, Emil von Behring isolated the diphtheria toxin and demonstrated its effects in guinea pigs. He went on to develop an antitoxin against diphtheria in animals and then in humans, which resulted in

4770-428: The PcG repressive complex 1 (PRC1) and the PcG repressive complex 2–4 (PRC2/3/4). PRC2 catalyzes trimethylation of lysine 27 on histone H3 (H3K27me2/3), while PRC1 mono- ubiquitinates histone H2A on lysine 119 (H2AK119Ub1). In mammals Polycomb Group gene expression is important in many aspects of development like homeotic gene regulation and X chromosome inactivation , being recruited to the inactive X by Xist RNA ,

4876-615: The United States by 1965. It has been estimated that developing and producing the vaccines required the use of 100,000 rhesus monkeys, with 65 doses of vaccine produced from each monkey. Sabin wrote in 1992, "Without the use of animals and human beings, it would have been impossible to acquire the important knowledge needed to prevent much suffering and premature death not only among humans, but also among animals." Other 20th-century medical advances and treatments that relied on research performed in animals include organ transplant techniques,

4982-430: The United States. Subsequent research in model organisms led to further medical advances, such as Frederick Banting 's research in dogs, which determined that the isolates of pancreatic secretion could be used to treat dogs with diabetes . This led to the 1922 discovery of insulin (with John Macleod ) and its use in treating diabetes, which had previously meant death. John Cade 's research in guinea pigs discovered

5088-546: The analog of norepinephrine. Acetylcholine is the primary excitatory neurotransmitter and GABA is the primary inhibitory neurotransmitter utilized in the drosophila central nervous system. In Drosophila, the effects of many neurotransmitters can vary depending on the receptors and signaling pathways involved, allowing them to act as excitatory or inhibitory signals under different contexts. This versatility enables complex neural processing and behavioral flexibility. Glutamate can serve as an excitatory neurotransmitter, specifically at

5194-438: The anticonvulsant properties of lithium salts, which revolutionized the treatment of bipolar disorder , replacing the previous treatments of lobotomy or electroconvulsive therapy. Modern general anaesthetics, such as halothane and related compounds, were also developed through studies on model organisms, and are necessary for modern, complex surgical operations. In the 1940s, Jonas Salk used rhesus monkey studies to isolate

5300-457: The basic knowledge in fields such as human physiology and biochemistry , and has played significant roles in fields such as neuroscience and infectious disease . For example, the results have included the near- eradication of polio and the development of organ transplantation , and have benefited both humans and animals. From 1910 to 1927, Thomas Hunt Morgan 's work with the fruit fly Drosophila melanogaster identified chromosomes as

5406-494: The behaviours associated with mate choice and the genetic contributions, such as production of gametes, that are exhibited by both male and female Drosophila regarding mate choice. Post copulatory strategies include sperm competition, mating frequency, and sex-ratio meiotic drive. These lists are not inclusive. Polyandry among the Drosophila pseudoobscura in North America vary in their number of mating partners. There

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5512-434: The brain is revealed. Drosophila brain structure and function develop and age significantly from larval to adult stage. Developing brain structures make these flies a prime candidate for neuro-genetic research. Many species, including the noted Hawaiian picture-wings, have distinct black patterns on the wings. The plumose (feathery) arista , bristling of the head and thorax, and wing venation are characters used to diagnose

5618-420: The causal relationship between genetic or environmental alterations and depression can be examined, which would afford a better insight into pathology of depression. In addition, animal models of depression are indispensable for identifying novel therapies for depression. Model organisms are drawn from all three domains of life, as well as viruses . The most widely studied prokaryotic model organism

5724-500: The components of the SNARE complex are known to be somewhat substitutable: Although the loss of SNAP-25 - a component of neuronal SNAREs - is lethal, SNAP-24 can fully replace it. For another example, an R-SNARE not normally found in synapses can substitute for synaptobrevin . The Spätzle protein is a ligand of Toll . In addition to melanin 's more commonly known roles in the endoskeleton and in neurochemistry , melanization

5830-439: The conservation of metabolic and developmental pathways and genetic material over the course of evolution . Research using animal models has been central to most of the achievements of modern medicine. It has contributed most of the basic knowledge in fields such as human physiology and biochemistry , and has played significant roles in fields such as neuroscience and infectious disease . The results have included

5936-465: The control of flowering by silencing the Flowering Locus C gene. This gene is a central part of the pathway that inhibits flowering in plants and its silencing during winter is suspected to be one of the main factors intervening in plant vernalization . Drosophila Oinopota Kirby & Spence, 1815 Drosophila ( / d r ə ˈ s ɒ f ɪ l ə , d r ɒ -, d r oʊ -/ )

6042-475: The decaying breeding substrate. Development time varies widely between species (between 7 and more than 60 days) and depends on the environmental factors such as temperature , breeding substrate, and crowding. Fruit flies lay eggs in response to environmental cycles. Eggs laid at a time (e.g., night) during which likelihood of survival is greater than in eggs laid at other times (e.g., day) yield more larvae than eggs that were laid at those times. Ceteris paribus ,

6148-530: The evolutionary tree. Historically, model organisms include a handful of species with extensive genomic research data, such as the NIH model organisms. Often, model organisms are chosen on the basis that they are amenable to experimental manipulation. This usually will include characteristics such as short life-cycle , techniques for genetic manipulation ( inbred strains, stem cell lines, and methods of transformation ) and non-specialist living requirements. Sometimes,

6254-556: The family. Most are small, about 2–4 millimetres (0.079–0.157 in) long, but some, especially many of the Hawaiian species, are larger than a house fly . Environmental challenge by natural toxins helped to prepare Drosophila e to detox DDT , by shaping the glutathione S -transferase mechanism that metabolizes both. The Drosophila genome is subject to a high degree of selection, especially unusually widespread negative selection compared to other taxa . A majority of

6360-421: The females, or form leks , conducting courtship in an area separate from breeding sites. Several Drosophila species, including Drosophila melanogaster , D. immigrans , and D. simulans , are closely associated with humans, and are often referred to as domestic species. These and other species ( D. subobscura , and from a related genus Zaprionus indianus ) have been accidentally introduced around

6466-531: The findings can be applied to deduce genetic trends in humans. Research conducted on Drosophila help determine the ground rules for transmission of genes in many organisms. Drosophila is a useful in vivo tool to analyze Alzheimer's disease. Rhomboid proteases were first detected in Drosophila but then found to be highly conserved across eukaryotes , mitochondria , and bacteria . Melanin's ability to protect DNA against ionizing radiation has been most extensively demonstrated in Drosophila , including in

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6572-455: The first to perform experiments on living animals. Discoveries in the 18th and 19th centuries included Antoine Lavoisier 's use of a guinea pig in a calorimeter to prove that respiration was a form of combustion, and Louis Pasteur 's demonstration of the germ theory of disease in the 1880s using anthrax in sheep. Research using animal models has been central to most of the achievements of modern medicine. It has contributed most of

6678-417: The flies were more cold resistant and also had the highest concentration of Wolbachia. The microbiome in the gut can also be transplanted among organisms. It was found that Drosophila melanogaster became more cold-tolerant when the gut microbiota from Drosophila melanogaster that were reared at low temperatures. This depicted that the gut microbiome is correlated to physiological processes. Moreover,

6784-523: The following three stages: insemination, sperm storage, and fertilizable sperm. Among the preceding species there are variations at each stage that play a role in the natural selection process. This sperm competition has been found to be a driving force in the establishment of reproductive isolation during speciation. Parthenogenesis does not occur in D. melanogaster , but in the gyn-f9 mutant, gynogenesis occurs at low frequency. The natural populations of D. mangebeirai are entirely female, making it

6890-608: The formative study by Hopwood et al. 1985. Like other animals, Drosophila is associated with various bacteria in its gut. The fly gut microbiota or microbiome seems to have a central influence on Drosophila fitness and life history characteristics. The microbiota in the gut of Drosophila represents an active current research field. Drosophila species also harbour vertically transmitted endosymbionts, such as Wolbachia and Spiroplasma . These endosymbionts can act as reproductive manipulators, such as cytoplasmic incompatibility induced by Wolbachia or male-killing induced by

6996-550: The genome arrangement facilitates the sequencing of the model organism's genome, for example, by being very compact or having a low proportion of junk DNA (e.g. yeast , arabidopsis , or pufferfish ). When researchers look for an organism to use in their studies, they look for several traits. Among these are size, generation time , accessibility, manipulation, genetics, conservation of mechanisms, and potential economic benefit. As comparative molecular biology has become more common, some researchers have sought model organisms from

7102-467: The genome is under selection of some sort, and a supermajority of this is occurring in non-coding DNA . Effective population size has been credibly suggested to positively correlate with the effect size of both negative and positive selection . Recombination is likely to be a significant source of diversity . There is evidence that crossover is positively correlated with polymorphism in D. populations. Drosophila species are found all around

7208-430: The geochemical and fossil record. These estimations tell us that humans and chimpanzees last shared a common ancestor about 6 million years ago (mya). As our closest relatives, chimpanzees have a lot of potential to tell us about mechanisms of disease (and what genes may be responsible for human intelligence). However, chimpanzees are rarely used in research and are protected from highly invasive procedures. Rodents are

7314-563: The guidance of animal models. Treatments for animal diseases have also been developed, including for rabies , anthrax , glanders , feline immunodeficiency virus (FIV), tuberculosis , Texas cattle fever, classical swine fever (hog cholera), heartworm , and other parasitic infections . Animal experimentation continues to be required for biomedical research, and is used with the aim of solving medical problems such as Alzheimer's disease, AIDS, multiple sclerosis, spinal cord injury, many headaches, and other conditions in which there

7420-460: The habit of laying eggs at this 'advantageous' time would yield more surviving offspring, and more grandchildren, than the habit of laying eggs during other times. This differential reproductive success would cause D. melanogaster to adapt to environmental cycles, because this behavior has a major reproductive advantage. Their median lifespan is 35–45 days. DNA damage accumulates in Drosophila intestinal stem cells with age. Deficiencies in

7526-540: The heart-lung machine, antibiotics , and the whooping cough vaccine. In researching human disease , model organisms allow for better understanding the disease process without the added risk of harming an actual human. The species of the model organism is usually chosen so that it reacts to disease or its treatment in a way that resembles human physiology , even though care must be taken when generalizing from one organism to another. However, many drugs, treatments and cures for human diseases are developed in part with

7632-428: The heart-lung machine, antibiotics , and the whooping cough vaccine. Treatments for animal diseases have also been developed, including for rabies , anthrax , glanders , feline immunodeficiency virus (FIV), tuberculosis , Texas cattle fever, classical swine fever (hog cholera), heartworm , and other parasitic infections . Animal experimentation continues to be required for biomedical research, and

7738-412: The host cells for propagation. In eukaryotes , several yeasts, particularly Saccharomyces cerevisiae ("baker's" or "budding" yeast), have been widely used in genetics and cell biology , largely because they are quick and easy to grow. The cell cycle in a simple yeast is very similar to the cell cycle in humans and is regulated by homologous proteins. The fruit fly Drosophila melanogaster

7844-904: The human equivalent. However complex human diseases can often be better understood in a simplified system in which individual parts of the disease process are isolated and examined. For instance, behavioral analogues of anxiety or pain in laboratory animals can be used to screen and test new drugs for the treatment of these conditions in humans. A 2000 study found that animal models concorded (coincided on true positives and false negatives) with human toxicity in 71% of cases, with 63% for nonrodents alone and 43% for rodents alone. In 1987, Davidson et al. suggested that selection of an animal model for research be based on nine considerations. These include 1) appropriateness as an analog, 2) transferability of information, 3) genetic uniformity of organisms, where applicable, 4) background knowledge of biological properties, 5) cost and availability, 6) generalizability of

7950-621: The immune systems of model organisms and humans that lead to significantly altered responses to stimuli, although the underlying principles of genome function may be the same. The impoverished environments inside standard laboratory cages deny research animals of the mental and physical challenges are necessary for healthy emotional development. Without day-to-day variety, risks and rewards, and complex environments, some have argued that animal models are irrelevant models of human experience. Mice differ from humans in several immune properties: mice are more resistant to some toxins than humans; have

8056-404: The laboratory, often because they breed on a single specific host in the wild. For some, it can be done with particular recipes for rearing media, or by introducing chemicals such as sterols that are found in the natural host; for others, it is (so far) impossible. In some cases, the larvae can develop on normal Drosophila lab medium, but the female will not lay eggs; for these it is often simply

8162-408: The laboratory. Some examples include: Spontaneous models refer to diseases that are analogous to human conditions that occur naturally in the animal being studied. These models are rare, but informative. Negative models essentially refer to control animals, which are useful for validating an experimental result. Orphan models refer to diseases for which there is no human analog and occur exclusively in

8268-584: The laws and guidelines governing the use of animals and research. In the U.S., the Animal Welfare Act of 1970 (see also Laboratory Animal Welfare Act ) set standards for animal use and care in research. This law is enforced by APHIS's Animal Care program. In academic settings in which NIH funding is used for animal research, institutions are governed by the NIH Office of Laboratory Animal Welfare (OLAW). At each site, OLAW guidelines and standards are upheld by

8374-434: The longest. D. melanogaster sperm cells are a more modest 1.8 mm long, although this is still about 35 times longer than a human sperm. Several species in the D. melanogaster species group are known to mate by traumatic insemination . Drosophila species vary widely in their reproductive capacity. Those such as D. melanogaster that breed in large, relatively rare resources have ovaries that mature 10–20 eggs at

8480-412: The majority of work with recombinant DNA . Simple model eukaryotes include baker's yeast ( Saccharomyces cerevisiae ) and fission yeast ( Schizosaccharomyces pombe ), both of which share many characters with higher cells, including those of humans. For instance, many cell division genes that are critical for the development of cancer have been discovered in yeast. Chlamydomonas reinhardtii ,

8586-505: The male and female. Recent experiments explore the role of fruitless ( fru ) and doublesex ( dsx ), a group of sex-behaviour linked genes. The fruitless ( fru ) gene in Drosophila helps regulate the network for male courtship behavior; when a mutation to this gene occurs altered same sex sexual behavior in males is observed. Male Drosophila with the fru mutation direct their courtship towards other males as opposed to typical courtship, which would be directed towards females. Loss of

8692-522: The master regulator of XCI or embryonic stem cell self-renewal. The Bmi1 polycomb ring finger protein promotes neural stem cell self-renewal. Murine null mutants in PRC2 genes are embryonic lethals while most PRC1 mutants are live born homeotic mutants that die perinatally. In contrast overexpression of PcG proteins correlates with the severity and invasiveness of several cancer types. The mammalian PRC1 core complexes are very similar to Drosophila. Polycomb Bmi1

8798-495: The microbiome plays a role in aggression, immunity, egg-laying preferences, locomotion and metabolism . As for aggression, it plays a role to a certain degree during courtship. It was observed that germ-free flies were not as competitive compared to the wild-type males. Microbiome of the Drosophila species is also known to promote aggression by octopamine OA signalling. The microbiome has been shown to impact these fruit flies' social interactions, specifically aggressive behaviour that

8904-474: The modern methods of immunization and largely ended diphtheria as a threatening disease. The diphtheria antitoxin is famously commemorated in the Iditarod race, which is modeled after the delivery of antitoxin in the 1925 serum run to Nome . The success of animal studies in producing the diphtheria antitoxin has also been attributed as a cause for the decline of the early 20th-century opposition to animal research in

9010-550: The most common animal models. Phylogenetic trees estimate that humans and rodents last shared a common ancestor ~80-100mya. Despite this distant split, humans and rodents have far more similarities than they do differences. This is due to the relative stability of large portions of the genome, making the use of vertebrate animals particularly productive. Genomic data is used to make close comparisons between species and determine relatedness. Humans share about 99% of their genome with chimpanzees (98.7% with bonobos) and over 90% with

9116-493: The most virulent forms of the polio virus, which led to his creation of a polio vaccine . The vaccine, which was made publicly available in 1955, reduced the incidence of polio 15-fold in the United States over the following five years. Albert Sabin improved the vaccine by passing the polio virus through animal hosts, including monkeys; the Sabin vaccine was produced for mass consumption in 1963, and had virtually eradicated polio in

9222-436: The mouse. With so much of the genome conserved across species, it is relatively impressive that the differences between humans and mice can be accounted for in approximately six thousand genes (of ~30,000 total). Scientists have been able to take advantage of these similarities in generating experimental and predictive models of human disease. There are many model organisms. One of the first model systems for molecular biology

9328-463: The near- eradication of polio and the development of organ transplantation , and have benefited both humans and animals. From 1910 to 1927, Thomas Hunt Morgan 's work with the fruit fly Drosophila melanogaster identified chromosomes as the vector of inheritance for genes, and Eric Kandel wrote that Morgan's discoveries "helped transform biology into an experimental science". Research in model organisms led to further medical advances, such as

9434-437: The neuromuscular junction in fruit flies. This differs from vertebrates, where acetylcholine is used at these junctions. In Drosophila, histamine primarily functions as a neurotransmitter in the visual system. It is released by photoreceptor cells to transmit visual information from the eye to the brain, making it essential for vision. As with many Eukaryotes, this genus is known to express SNAREs , and as with several others

9540-412: The only obligate parthenogenetic species of Drosophila. Parthenogenesis is facultative in parthenogenetica and mercatorum . D. melanogaster is a popular experimental animal because it is easily cultured en masse out of the wild, has a short generation time, and mutant animals are readily obtainable. In 1906, Thomas Hunt Morgan began his work on D. melanogaster and reported his first finding of

9646-423: The other. Females have little control when it comes to cryptic female choice . Female Drosophila through cryptic choice, one of several post-copulatory mechanisms, which allows for the detection and expelling of sperm that reduces inbreeding possibilities. Manier et al. 2013 has categorized the post copulatory sexual selection of Drosophila melanogaster , Drosophila simulans , and Drosophila mauritiana into

9752-454: The overwhelming majority of studies, while the human population is heterogeneous, pointing to the importance of studies in interstrain hybrid, outbred , and nonlinear mice. Some studies suggests that inadequate published data in animal testing may result in irreproducible research, with missing details about how experiments are done omitted from published papers or differences in testing that may introduce bias. Examples of hidden bias include

9858-451: The production of the diphtheria antitoxin and the 1922 discovery of insulin and its use in treating diabetes, which had previously meant death. Modern general anaesthetics such as halothane were also developed through studies on model organisms, and are necessary for modern, complex surgical operations. Other 20th-century medical advances and treatments that relied on research performed in animals include organ transplant techniques,

9964-686: The relationship between human and fruit fly genes is very close. Human and fruit fly genes are so similar, that disease-producing genes in humans can be linked to those in flies. The fly has approximately 15,500 genes on its four chromosomes, whereas humans have about 22,000 genes among their 23 chromosomes. Thus the density of genes per chromosome in Drosophila is higher than the human genome. Low and manageable number of chromosomes make Drosophila species easier to study. These flies also carry genetic information and pass down traits throughout generations, much like their human counterparts. The traits can then be studied through different Drosophila lineages and

10070-505: The results, 7) ease of and adaptability to experimental manipulation, 8) ecological consequences, and 9) ethical implications. Animal models can be classified as homologous, isomorphic or predictive. Animal models can also be more broadly classified into four categories: 1) experimental, 2) spontaneous, 3) negative, 4) orphan. Experimental models are most common. These refer to models of disease that resemble human conditions in phenotype or response to treatment but are induced artificially in

10176-476: The same causes, symptoms and treatment options as would humans who have the same disease, isomorphic animals share the same symptoms and treatments, and predictive models are similar to a particular human disease in only a couple of aspects, but are useful in isolating and making predictions about mechanisms of a set of disease features. The use of animals in research dates back to ancient Greece , with Aristotle (384–322 BCE) and Erasistratus (304–258 BCE) among

10282-469: The species studied. The increase in knowledge of the genomes of non-human primates and other mammals that are genetically close to humans is allowing the production of genetically engineered animal tissues, organs and even animal species which express human diseases, providing a more robust model of human diseases in an animal model. Animal models observed in the sciences of psychology and sociology are often termed animal models of behavior . It

10388-405: The stomach, attempt to copulate, and the copulatory act itself. The songs of Drosophila melanogaster and Drosophila simulans have been studied extensively. These luring songs are sinusoidal in nature and varies within and between species. The courtship behavior of Drosophila melanogaster has also been assessed for sex-related genes, which have been implicated in courtship behavior in both

10494-581: The study of disease. Cell culture, or in vitro studies, provide an alternative that preserves the physiology of the living cell, but does not require the sacrifice of an animal for mechanistic studies. Human, inducible pluripotent stem cells can also elucidate new mechanisms for understanding cancer and cell regeneration. Imaging studies (such as MRI or PET scans) enable non-invasive study of human subjects. Recent advances in genetics and genomics can identify disease-associated genes, which can be targeted for therapies. Many biomedical researchers argue that there

10600-491: The use of computer models, non-living tissues and cells, and replacement of “higher-order” animals (primates and mammals) with “lower” order animals (e.g. cold-blooded animals, invertebrates) wherever possible. "Reduction" refers to efforts to minimize number of animals used during the course of an experiment, as well as prevention of unnecessary replication of previous experiments. To satisfy this requirement, mathematical calculations of statistical power are employed to determine

10706-483: The vector of inheritance for genes. Drosophila became one of the first, and for some time the most widely used, model organisms, and Eric Kandel wrote that Morgan's discoveries "helped transform biology into an experimental science". D. melanogaster remains one of the most widely used eukaryotic model organisms. During the same time period, studies on mouse genetics in the laboratory of William Ernest Castle in collaboration with Abbie Lathrop led to generation of

10812-489: The world by human activities such as fruit transports. Males of this genus are known to have the longest sperm cells of any studied organism on Earth, including one species, Drosophila bifurca , that has sperm cells that are 58 mm (2.3 in) long. The cells mostly consist of a long, thread-like tail, and are delivered to the females in tangled coils. The other members of the genus Drosophila also make relatively few giant sperm cells, with that of D. bifurca being

10918-780: The world, with more species in the tropical regions. Drosophila made their way to the Hawaiian Islands and radiated into over 800 species. They can be found in deserts , tropical rainforest , cities , swamps , and alpine zones . Some northern species hibernate . The northern species D. montana is the best cold-adapted, and is primarily found at high altitudes. Most species breed in various kinds of decaying plant and fungal material, including fruit , bark , slime fluxes , flowers , and mushrooms . Drosophila species that are fruit-breeding are attracted to various products of fermentation, especially ethanol and methanol . Fruits exploited by Drosophila species include those with

11024-417: Was the bacterium Escherichia coli , a common constituent of the human digestive system. Several of the bacterial viruses ( bacteriophage ) that infect E. coli also have been very useful for the study of gene structure and gene regulation (e.g. phages Lambda and T4 ). However, it is debated whether bacteriophages should be classified as organisms, because they lack metabolism and depend on functions of

11130-569: Was the first plant to have its genome sequenced . Among vertebrates , guinea pigs ( Cavia porcellus ) were used by Robert Koch and other early bacteriologists as a host for bacterial infections, becoming a byword for "laboratory animal", but are less commonly used today. The classic model vertebrate is currently the mouse ( Mus musculus ). Many inbred strains exist, as well as lines selected for particular traits, often of medical interest, e.g. body size, obesity, muscularity, and voluntary wheel-running behavior. The rat ( Rattus norvegicus )

11236-480: Was vastly used in genetics. However, the effect abiotic factors , such as temperature, has on the microbiome on Drosophila species has recently been of great interest. Certain variations in temperature have an impact on the microbiome. It was observed that higher temperatures (31 °C) lead to an increase of Acetobacter populations in the gut microbiome of Drosophila melanogaster as compared to lower temperatures (13 °C). In low temperatures (13 °C),

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