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Modern Genetics for Policymakers Lecture Series – S M Saminathan – Medium

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The similarity between the Drosophila genome and the human genome has enabled several researchers in the past century to unravel the enigmas of modern genetics. In the past hundred years, five Nobel prizes for physiology or medicine were awarded for pathbreaking works in the fruit flies. Thomas Morgan laid the foundation for modern genetics by experimentally confirming the location of genes on chromosomes and heredity. The study by Muller established that X-rays caused mutations in fruit flies. His research created global awareness in radiation exposure safety and unlocked the X-ray induced mutation universe. Recent research works on Drosophila revealed the essential genes that controlled early embryonic development. These works established that some genes are evolutionarily conserved and play an indispensable role in the development of embryos and segmentation. The genetic control of immunity and the underlying mechanism was also first discovered in the fruit flies. This discovery has led to an improved understanding of several diseases and developing an appropriate immune response. The genetic and molecular mechanism behind the circadian rhythm was the most recent discovery awarded the Nobel prize for physiology or medicine that used the fruit flies as the model organisms. Drosophila based experiments have also made progress in Cancer and Alzheimer’s’ research. Several studies in comparative and evolutionary genomics to demystify fundamental mechanisms in general biology show that Drosophila and its contributions to making the world a better place are far from over.

Introduction

Drosophila melanogaster Meigen; (Diptera: Drosophilidae) is an indispensable insect in medical research as its DNA exhibits sixty percent similarity with the human DNA. This similarity has enabled several prominent advancements in understanding human genetics and general biology. Drosophila is tiny, economical to manage and is easy to manipulate in the laboratory. The life cycle of the fruit flies takes only two weeks to complete. This short period has been a fantastic advantage for scientists across the world to design and perform experiments for studying several generations rapidly. Also, the Drosophila consists of only four pairs of chromosomes in its genome compared to twenty-three pairs in humans. The presence of fewer chromosomes has made gene manipulation and improved understanding of genes after mutation possible. The question of how particular genes interact with each other is also easily explained with Drosophila thus making it an ideal model organism for several genetic experiments in the past century.

Alfred Nobel was an important innovator and entrepreneur of his time. He had over three hundred and fifty-five patents to his credit with the most famous patent being the patent for dynamite. Over the years he had built various companies and had amassed sizable wealth. Alfred Nobel left an enormous sum of his wealth for the establishment of the Nobel prizes. As stated in his will five prizes were established and presented to the most qualified people who had helped advance humankind. From 1901 to 2018, five prizes for physiology or medicine were bestowed for pathbreaking works based on Drosophila. In the early 20th century Thomas Morgan used the fruit flies to prove the location of the genes in the chromosomes. His work on genes and heredity laid the foundation for modern genetics. He was the first person to secure the Nobel prize in 1933 for his work based on Drosophila. After Thomas Morgan, Hermann Joseph Muller won the prize in 1946 for his work on Drosophila in understanding the ability to increase mutation rates through irradiation by X-rays. In the past 20 years alone, scientists won three more Nobel prizes for their work based on fruit flies. In 1995, Edward B Lewis and his team employed Drosophila to discover and explain the genetic mechanisms and regulations behind embryonic development. The Nobel committee chose Jules A Hoffmann’s research on the activation of innate immunity on Drosophila for the year 2011. Most recently in 2017, the discovery of molecular mechanisms behind the circadian rhythms in Drosophila was honored with the Nobel prize.

Drosophila biology

More than seventy percent of human disease related genes are conserved in Drosophila (Rubin et al.,2000). All developmental stages of the fruit flies from the embryo stage to the adult stage are very useful for conducting genetic experiments (Pandey et al., 2011). The embryos of fruit flies undergo nine nuclear division cycles to form a cellular blastoderm. The cycles are composed of G and S phases, and each cycle takes only ten minutes to complete. The segmentation process immediately follows cellularization (Yamaguchi et al., 2018). Molecular pattern formation, cell fate perception, understanding the structure and molecular mechanism behind the formation of different organs and nervous system development are understood via experiments involving the embryo (Yamaguchi et al., 2018). The third instar larvae are usually employed to investigate foraging and several physiology related mechanisms. For research on cell cycles, eye imaginal discs in the larval stage are particularly useful. Imaginal discs are a group of cells primarily composed of an undifferentiated epithelium that produces adult body structures such as eyes, wing, and antennae. Various training and memory- retention are also feasible in the larval stage of the fruit flies.

During the pupal stage, most larval cells undergo apoptosis, while the imaginal discs are transformed into distinct organs as a result of hormonal changes happening in the larvae (Yamaguchi et al., 2018). The firm control of multiple cellular pathways in the pupal stage is useful for studying complex genetic mechanisms. Many of the adult fruit fly bodies and organs are similar to its mammalian counterparts. This similarity has long aided in research and development of various solutions to complex problems occurring in the mammalian bodies (Yamaguchi et al., 2018). The fruit fly nervous system has over a hundred thousand neurons enabling the fruit flies to exhibit mammalian brain cell like effects when treated with neuropathic drugs. The circadian rhythms, learning capabilities, ingestion of food and courtship are all crucial aspects of the Drosophila that makes it one of the ideal model organisms for genetic research (Yamaguchi et al., 2018).

In the past one hundred years, Drosophila has been a vital organism for fundamental research in genetics. It is believed with reasonable proof that the fruit flies genes share over seventy-five percent similarity with disease-causing human genes (Pandey et al., 2011). The comparison between Drosophila and human genome too exhibited substantial homologies, thus confirming the genetic importance of the fruit flies (Yamaguchi et al., 2018). At the nucleotide level, the similarity is around forty percent, while comparing the conserved functional domains of the proteins there is an astounding eighty percent match (Yamaguchi et al., 2018). Hence, the fruit flies have always been at the vanguard of modern genetics, where all primary genetic engineering tools are first tried and tested in Drosophila before generalizing to all other animals and plants. A single pair of fruit flies can produce hundreds of genetically identical progenies within ten days which is much faster and efficient than the rodent model (Yamaguchi et al., 2018). Drosophila contains balancer chromosomes. The balancer chromosomes carry inversions that inhibit the recovery of chromosome exchange events. As a result, the sequences in the balancer and balanced chromosomes are isolated and maintained. Also, the balancer chromosomes do not limit crossing over. The balancer chromosomes manage lethal and sterile mutations. The balancer chromosomes in the fruit flies can also be used for screening for mutations (Yamaguchi et al., 2018).

Foundation for modern genetics and heredity

Thomas Hunt Morgan experimentally confirmed that genes are located on chromosomes inside the nucleus of the cell by conducting experiments on the inheritance of genetic traits in Drosophila. He also discovered the crossover of small sections of chromosomes with one another. For his extensive work on chromosomes and heredity, he won the Nobel Prize in 1933. While working at Columbia University, Thomas Hunt Morgan set up the fly lab with Drosophila so that the transmission of genetic traits through successive generations can be studied. During a routine observation, he noted that a male fruit fly had developed white eyes instead of the usual bright red. He was curious about the whole situation so he set up a breeding line of the Drosophila with white eyes so that the trait could be analyzed. Through the works that followed for a total period of over seventeen years, Morgan was able to prove that a specific trait’s inheritance had linkage to a particular gene on the chromosomes (Miko, 2008).

While studying the inheritance of the white eyes trait, Morgan discovered an abnormal inheritance pattern, so he performed a test cross between the white-eyed trait bearing male and many thoroughbred red-eyed Drosophila to see if there is an inheritance of the trait (Miko, 2008). All the resulting F1 generation were purely red-eyed progenies. In a second test cross, red-eyed male and female from the F1 generation were crossed (Miko, 2008). This cross produced a three to one proportion of red to white, indicating that white was not dominant. This result was in lines with Mendelian genetics. Also, all the offspring had male pattern white eyes. Further analysis revealed that all the white-eyed Drosophila formed in the F2 generation were males with no exception. This correlation of a nonsexual trait like eye color with the sex of the insect is the first of its kind. The hypothesis is that the white eyes trait induced lethality in female Drosophila leading to the production of male progenies with white eyes. A third test cross between F1 females with red eyes and males with white eyes was done and analyzed. The results proved that the white-eyed trait was not lethal to female flies and all combinations of white-eyed flies and sex as feasible.

In the fourth test cross, the question of whether the white eyed characteristic also follows the inheritance of the X-chromosome from the maternal gametes was addressed by performing a reciprocal F1 cross. The fourth test cross developed all white eye males and all red eye females because the white eye female mother would most certainly be homozygous recessive as the white eye was found to be a recessive trait compared to the red-eye trait from previous test crosses (Miko, 2008). Also as female progenies inherit the only X chromosome from the male parent, it was evident that the female progenies would be red-eyed. Hence, even though for many years Morgan was an influential critic of the chromosomal theory of inheritance (Morgan,1909) through all these experiments in Drosophila, he and his team was able to give experimental proof for the first time that traits inherited in progenies via chromosomal factors similar to the inheritance of sex chromosomes (Miko, 2008).

X-rays and Mutation

Mutation is a sudden change in a living organism’s genetic code. It usually occurs as a result of an external influence such as a mutagen. Hermann Joseph Muller was the first to explain that the rate of mutation in genes of the Drosophila increase when exposed to X rays (Muller, 1927). He demonstrated linearity where the higher the dosage of X-rays exposure led to increased mutation rates in Drosophila (Muller, 1928). For this discovery, Muller earnt the Nobel Prize for the year 1946. Earlier he studied genetic mutations and the structure of chromosomes in fruit flies in Morgan’s fly lab and helped discover a class of genes called marker genes that let investigators identify specific loci in the genome, even after altering the chromosomes or genes (Gleason, 2017). Before his experiments using X-rays for mutation, Muller examined temperature as a potential mutagen. He developed a method to quantify the incidence of mutations in terms of numbers and frequency. This method was also used in his later experiments while using X-rays (Gleason, 2017).

Muller performed three experiments that demonstrated the increased mutation rates phenomenon in egg and sperm cells of Drosophila. In his first experiment, the chosen genetic marker was the bobbed bristles (bb) genes on the X-chromosome. The bb gene produced irregularities in the shape of the flies’ sensory bristles. Female flies had both X-chromosomes carrying the scv f gene which produced a different eye color and distinctly altered sensory bristles. Both the flies were exposed to X-rays and then allowed to mate resulting in heterozygous females, i.e., the females had both the genes, while the males only had the scv f gene. As the bb genes were recessive, they were not expressed but still carried in the females. To observe the effect of the X-rays on the F2 generation, the F1 generation was crossed (Gleason, 2017). The hypothesis is that the radiation-induced mutation was lethal in the fruit flies initially exposed to the X-rays if the males in F2 generation lacked the bb gene and only had scv f gene. Another hypothesis is that the radiation-induced mutation was lethal in the fruit flies initially exposed to the X-rays if the males in the F2 generation lacked the scv f gene and only had bb gene. Upon observation of the one thousand cultures and one thousand control, it was evident that the mutations did not appear spontaneously as eighty-eight out of seven hundred and fifty-eight cultures had lethal mutations. This number is very high compared to the control group where only one lethal mutation was observed among nine hundred and forty-seven cultures (Muller, 1928).

In the second experiment, the chosen genetic markers were X-linked ClB genes that are lethal to male fruit flies. By controlled mating, F2 fruit flies with male progenies inheriting either X-chromosomes with the lethal ClB gene or X-chromosomes from radiation exposed parents were bred (Gleason, 2017). The hypothesis is that if the previous generation has developed lethal mutations in the X-chromosomes, then no living male offspring would be produced. By calculating the fraction of male and female progenies in the F2 generation, it was evident that the X-ray exposure was lethal. Also, X-ray exposure caused one hundred and fifty times more lethality through a lethal mutation as opposed to the spontaneous lethality through lethal mutations that befell in the control group (Muller, 1928). In the third experiment, the progenies of X-ray exposed Drosophila exhibited visible mutations. The chosen female fruit flies had two X-chromosomes fused into one and a Y-chromosome. The chosen male fruit flies had X-linked bb gene and were subjected to X-rays.

Upon crossing and observation, instead of normal inheritance where the males inherit the maternal X- chromosome, paternal X-chromosomes and maternal Y-chromosome were inherited (Muller, 1928). As a result, all non-lethal mutations in the male parent can are visible in the F1. The frequency of the visible mutations was higher in fruit flies exposed to X-rays than the spontaneously occurring mutations even though the abnormal phenotypes like the change in eye color, change in shape of bristles and wings remained the same (Gleason, 2017). This discovery that X-rays induced genes to mutate had vast implications. Even as early as the beginning of the 20th century the applications of the X-rays expanded into medical, dental, and industrial fields (Gleason, 2017). In radiology, Muller’s work explained the risks of X-rays. It revealed that X-rays could hinder reproductive potential. Only after his discovery precautions were taken to protect people in hospitals from X-rays as it can affect sperm and egg cells in addition to hindering embryo development (Gleason, 2017). In genetics, his research demonstrated that environmental agents like radiation could affect heritable traits. This historic discovery has led to unprecedented advancement in every aspect of gene editing where induced mutations were previously impossible (Gleason, 2017).

Genes that control early embryo development

In 1995, three scientists were conferred the Nobel prize for their work on revealing the critical genetic mechanisms of early embryonic development. Volhard and Wieschaus recognized and classified Drosophila genes that are very important in defining the body blueprint and the formation of segments. Scientist Lewis separately explored the genetic mechanisms behind the development of body segments and specialized organs. He discovered the curious phenomenon that on the chromosomes genes are prearranged in the similar sequence as the segments they controlled. Hence, in a developmental genes complex, the first genes control the head region, followed by the genes controlling the abdominal area and the genes controlling the posterior regions of the end of the complex of developmental genes.

Through their work, the three scientists have helped understand the congenital malformations in humans. In (Nüsslein-Volhard & Wieschaus, 1980) lethal embryonic mutants in fruit flies were identified at fifteen different loci. These genes when mutated alter the segmentation in the larvae. Pattern duplication, pattern deletion in adjacent segments and pattern deletion in alternating segments are the alterations observed. Also, three classes of loci affecting segmentation are described in the research. The are segment polarity mutants, Pair-rule mutants and gap mutants.

The first class is the segment polarity mutants that effect deletions in each segment. Genetic Mutants in this class of loci appear to have a normal amount of segments. Upon analysis, however, it is evident that a fraction of the regular pattern is deleted in each segment and the remaining fragment is duplicated in the form of a mirror-image (Nüsslein-Volhard & Wieschaus, 1980). Six such loci have been identified in this class and the characteristic feature of all mutants is that a defined fraction of the pattern in each segment is deleted. As this deletion comes with the duplication with a mirror image of the residual fragment of the pattern it is confirmed that the loci are involved in the designation of the fundamental pattern of the segments (Nüsslein-Volhard & Wieschaus, 1980).In the Pair-rule mutants class, homologous fragments of each of the six loci are distinguished by its own specific pattern of deletions in alternating segments. The identification of the fragments existing or eliminated in the mutant larvae is done by analysing the phenotypes produced in alleles that have low expressivity (Nüsslein-Volhard & Wieschaus, 1980). In the class of Gap mutants, one unbroken stretch of segments deleted. Alteration is not repeated at particular intervals along the axis of the embryo-like the first two classes of mutants. However, up to eight contiguous segments are deleted from the concluding pattern. Three loci causing such gaps in the pattern were found (Nüsslein-Volhard & Wieschaus, 1980). It is experimentally verified that all the three loci are needed for a normal segmental subdivision of one continuous body section.

In (Lewis, 1978) it was identified that the bithorax gene complex in the fruit flies contains at least eight genes that encode for regulating thoracic and abdominal development. He also explained how homeotic genes interact with each other and how the gene order matched with the segment order along the fruit fly’s body axis (Lewis, 1978). Several genes investigated by Nüsslein-Volhard, Wieschaus, and Lewis are responsible for embryo polarity and body segmentation (Lewis, 1978; Nüsslein-Volhard & Wieschaus, 1980). Understanding congenital malformations in humans was an important application of their discovery. Mutations in critical genes were found to be the primary reason. Other important applications in understanding human diseases include Waardenburg’s syndrome that causes deafness, facial bone defects, and iris pigment alteration. Aniridia which results in a complete loss of the iris is also found to be caused by a genetic mutation (Lewis,1995). Thus, the work of all three scientists have broadened the understanding of evolutionarily conserved strategies that control early embryo development.

Genetic control of immunity

The Nobel Prize for 2011 was divided into two halves, with the first half awarded to Jules Hoffmann and Bruce Beutler for path breaking research in discovering receptor proteins that are responsible for triggering innate immune responses. The second half of the Nobel prize was awarded to Ralph Steinman for his discovery of the role of dendritic in adaptive immunity. Their study has enabled the humankind by answering several questions that help in the understanding of the immune system. The components of the immune system were discovered by the string of findings that were awarded the Nobel prize like the mechanism behind the construction of antibodies and the mechanism behind the recognition of foreign substances by T cells. However, the mechanisms that trigger innate immunity and mediate the interaction between the innate immune system and adaptive immune system was not known until the discoveries of Bruce Beutler, Jules Hoffmann, and Ralph Steinman. Jules Hoffmann and his team were investigating how fruit flies combat infections. In addition to using mice for their research, they also used flies with mutations including essential genes like toll, an essential gene for embryonal development as discovered by Volhard the winner of Nobel Prize for medicine 1995.

Insects have beneficial host defense mechanisms against invading pathogens. Coagulation is immediately induced after injury followed by encapsulation of the pathogens by the blood cells; and the synthesis of powerful antimicrobial peptides (Lemaitre et al.,1996). There are two functionally distinct classes of peptides, one for antibacterial peptides and another for antimicrobial peptides. The mechanism that controls the triggering of this peptide synthesis was the key still elusive. In (Lemaitre et al.,1996) the expression of anti-fungal peptide genes and anti-bacterial peptide genes was analyzed. This examination was done in strains bearing mutants that alter dorso-ventral pattern in the Drosophila embryo. It is evident that the embryo regulatory genes Toll ligand, spätzle, and cact play a substantial part in the governing drosomycin the antifungal peptide gene (Lemaitre et al.,1996). The presence of significant variations in the control of antibacterial peptides and antifungal peptides expression was also explained. In adult fruit flies two different kinds of mutants were examined. Mutants with loss of function mutations producing completely dorsalized embryos and gain of function mutations in Toll and loss-of-function mutations in cact that are ventralizing were chosen (Lemaitre et al.,1996). The dorsalizing mutants were tested with a bacterial injection that stimulates antifungal and antibacterial gene expression while the ventralizing mutants were investigated in the absence of injection. Later Northern blot analysis was performed to examine the anti-microbial gene expression. The manifestation of the dorsoventral signaling genes was also studied (Lemaitre et al.,1996). Results from various experiments confirmed that mutations affecting various genes that enable the production of anti- microbial peptides to reduce the resistance to microbial infection to a large extent (Lemaitre et al.,1996). Thus the mechanism that triggers innate immunity was explained. The role of the Toll gene as an essential defense mechanism trigger and the necessity of Toll activation for mounting a successful

defense was also experimentally proven by Hoffmann. Bruce Beutler while working on mice found aToll-like receptor that helped in bacterial binding (Poltorak et al., 1998). Ralph Steinman confirmed that dendritic cells activate T-cells in mice (Steinman & Witmer, 1978). The insights from these discoveries have helped in understanding the immune system; thus enabling the development of new techniques for preventing and managing diseases. Improved vaccines development and stimulation of the immune system to attack tumors are some of the examples that were a result of this path-breaking research. These discoveries also help in discovering newer approaches to handle inflammatory diseases.

Biological clock

The Nobel Assembly awarded Jeffrey Hall, Michael Rosbash and Michael Young the Nobel prize for the year 2017 for discovering the mechanisms that control the rhythm of the biological clock. Using Drosophila the gene that controls the normal functioning of the daily biological rhythm was discovered. It is demonstrated that a particular gene locus codes for the protein that collects inside the cell throughout the night and is subsequently deteriorated in the day. Additional components managing the self-sustaining biological clock inside individual cells were also identified. Seymour Benzer and Ronald Konopka were the first to recognize genetic control of circadian cycle in Drosophila. They experimentally confirmed that fruit fly mutants with gene locus named per period on the X chromosome disrupted their biological clock (Konopka & Benzer, 1971). In three classes of per mutations were found. The first class is perl mutants with a longer twenty nine hour circadian rhythm period than the usual twenty four hour period. The second class of per mutants was pers mutants. They have shorter rhythm period of around nineteen hours. The third class of mutants per0 had no detectable circadian rhythms (Konopka & Benzer, 1971). Further experiments revealed that all mutants also exhibited variation in the periodicity of male courtship songs (Kyriacou et al.,1980). In (Zehring et al.,1984) it was found that mutations at the per locus disrupt several biological rhythms in Drosophila including the change in length and frequency of courtship song rhythms in males. Changes in circadian locomotor behavior and eclosion was also observed (Bargiello et al., 1984). When transformants were used to insert subsegments of the per gene to mutant arrhythmic Drosophila the rhythmicity was restored in both the experiments (Bargiello et al., 1984; Zehring et al.,1984). In (Siwicki et al., 1988) antibodies were developed for the per gene using small peptides of the sequence as immunogens. Specific staining was identified in diverse tissue types on per protein including the embryonic CNS, cellular bodies in the brain of the Drosophila pupae, imaginal cells, optic lobes, and the gut. It was experimentally verified that the intensity of the staining in the visual system was observed to waver peaking in the night (Siwicki et al.,1988).

In (Hardin et al.,1990) Drosophila mutants in the per gene exhibited changes in the circadian and ultradian cycles. It was hypothesized that the per protein regulated the period gene. It was demonstrated that the mRNA levels also oscillate in addition to the gene product levels (Hardin et al., 1990). This indicates that the PER protein cycling could be a product of the per RNA cycling. The reason behind this connection is the presence of an inhibitory feedback loop through which the per protein prevents its own synthesis (Hardin et al., 1990). Therefore when the per gene is expressed, period mRNA is produced. This mRNA is the template for the per protein which is later accumulated in the nucleus. Also as the period gene expression is barred in the nucleus, an inhibitory feedback mechanism is developed resulting in the circadian rhythm. It was later found that the per protein reached the nucleus with the help of another protein called TIM (Vosshall et al.,1994). This protein is produced by the expression of the timeless gene. when the two proteins TIM and per joined together they enter the nucleus and complete the feedback loop that inhibits the period gene activity (Vosshall et al.,1994). The frequency of the oscillation was controlled by the expression of another gene named doubletime.Doubletime codes for DBT protein that assists in delaying the buildup of the per protein (Price et al.,1998). After these discoveries circadian biology became a meticulous and dynamically evolving field in humans and many other organisms. The biological clock controls important functions like behavior, hormonal levels, rest, body heat and metabolism. With the understanding of the molecular mechanism many of these fundamental aspects of human well-being can be improved.

Discussion

Fundamental knowledge obtained from research in Drosophila is useful for curing various ailments. Drosophila based genetic tools are available for a vast array of fundamental research. One such critical tool is the genetic mosaic technique (Xu & Rubin,1993). Later this tool was modified to establish mosaic analysis with a repressible cell marker (MARCM) system. Using the genetic mosaic technique, somatic clones of mutants can be induced in living cells. This tool allows the co-existence of cells with different genetic makeup in the same living organism which is very useful for cancer research (Enomoto et al.,2018). Research in Drosophila led to the discovery of the cell death mechanism that occurs in all living organisms (Orme et al., 2009). This mechanism also called apoptosis is triggered when a cell gets damaged beyond repair. As a result, the cells die in a suicide mission leaving the healthy cells to survive and take up the reusable contents. This programmed cell death is not triggered in cancer cells, thus assisting in the rapid tumor development process. Recent research in fruit flies has confirmed that the heightened levels of molecules called inhibitors of apoptosis proteins are the primary reason why cancer cells develop and lead to the development of tumor cells (Orme et al., 2009). This discovery holds promise in human cancer research and can be very useful in drug discovery to target the inhibitors of apoptosis proteins levels thereby preventing cancer cells from spreading. Similarly, many cancer suppressor genes that were initially identified in Drosophila were subsequently detected, and their homologs were proven to play important roles in oncogenesis in human cancer research (Yamaguchi et al., 2018). Drosophila is also used for studying tumor formation and metastasis as a cancer model. In recent times drosophila has also become one of the model important model organisms for cancer drug discovery and the evaluation of compound pharmacodynamics (Akasaka & Ocorr, 2009; Gao et al., 2014).

In recent times, nervous system related experiments can be efficiently designed and executed using Drosophila. This capacity of Drosophila has enabled in improving the understanding of neurodegeneration and Alzheimer’s in humans. Alzheimer’s disease affects older adults leading to neurodegeneration and memory defects (Tsuda et al.,2018). Beta-amyloid (Aβ) is the truncated peptide responsible for disease formation. Experiments on the fruit flies have demonstrated that the rapid degradation of the nerve cells (axons) is responsible for neurological diseases like Alzheimer’s. A vast number of model systems are established using Drosophila by altering the production of Aβ molecules in the brain (Tsuda et al.,2018). Also, several mutants and transgenic Drosophila lines can be obtained from stock centers across the world such as the Bloomington Drosophila Stock Center , Vienna Drosophila Resource Center and the Exelixis Collection. Drosophila is used to study human diseases for recognizing unique biomarkers and targets for therapy. They are also used for screening candidate drugs for treatment. The main limitation in using Drosophila is that it does not have hemoglobin, so experiments around diseases involving hemoglobin cannot be studied using the fruit fly models. Mammalian models like rodents are used in such cases. The sequencing of the fruit fly genome was completed recently (Adams et al., 2000). The initial annotation and identification revealed thirteen thousand six hundred genes out of which two thousand five hundred were already characterized. Twenty years down the lane these numbers would be higher now. Several species of Drosophila were studied in the past. Drosophila pseudoobscura Frolova; (Diptera: Drosophilidae) is another important species that was used extensively in evolutionary genetics research. Chromosomal inversions and the possibility of the evolution of new organisms was also understood primarily due to fundamental research involvingD. pseudoobscura (Sturtevant & Dobzhansky, 1936). Several more Drosophila species like D. simulans, D. grimshawi also have critical aspects that hold clues for understanding the world of genetics in the years to come (Hales et al., 2015). In this way, Drosophila holds promise for not only in medical research but also in comparative and evolutionary genomics for discovering functional elements in genomes that can further enhance life on earth.

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