Wednesday, May 6, 2020
JFK WAS GOOD. THATS WHY THEY KILLED HIM Essay Example For Students
JFK WAS GOOD. THATS WHY THEY KILLED HIM Essay JFkIm reminded of the expression out of the mouths of babes whenever I think about the question my son asked me one day when I was talking about JFK. It was in November 1988 and I had just bought LIFE magazines special 25th Anniversary edition of the assassination of President Kennedy. I was sitting on the couch looking at the pictures when my two sons came home from school. They sat down beside me and I started telling them about JFK but I couldnt stop crying. One of them asked me why I was still crying after all these years. I told them that it was because JFK was so good and the people who killed him were so bad but JFK was gone and the people who killed him were still here. Then my littlest son asked, Mommy, if President Kennedy was so good then why did they kill him?I was just about to go into a long explanation when it occurred to me that the answer was actually contained in the question and I replied, President Kennedy was good. Thats why they killed him.Several years later I was reading Arthur Schlesingers classic, A THOUSAND DAYS, and was struck by the truth of the dedication he chose. It was a quote from Ernest Hemingway:If people bring so much courage to this worldthe world has to kill them to break themso of course it kills them. The world breaks every one and afterwardmany are strong at the broken places. But those that will not break it kills. It kills the very good and the very gentleand the very brave impartially. In the years since 1988 Ive been trying to teach people the truth about JFK. Ive found that the only way to de-program them from the lies theyve been told is to tell them to snap out of it and start thinking. I ask them if they would trust the people who blew JFKs brains out in broad daylight to tell them the truth about anything. Most assure me they wouldnt. I tell them that there is a strong body of evidence suggesting that the same people who arranged the assassination of JFK now own most of the mainstream media and use that media to tell lies about JFKs life and death. They pay authors to write the books and documentaries that tell the lies. I then suggest they go and read 1984 because Orwell is proving to be very accurate in many of his convictions. I tell them that in 1984 Orwell told us that: BIG BROTHER (the Party) owned the print media, as well as film and radio; and used it to twist reality into whatever shape it chose. The Ministry of Truth (Lies) supplied the citizens of Oceania with newspapers, films, textbooks, telescreen programmes, plays, novels with every conceivable kind of information, instruction, or entertainment. Anonymous directing brains co-ordinated the whole effort and laid down the laws of policy which made it necessary that this fragment of the past should be preserved, that one falsified, and the other rubbed out of existence.I also remind people to trust the reality of their own senses and remember how they felt the day JFK died. If they are old enough most of them remember where they were when they heard JFK had been shot. Lots of people who werent even BORN remember the day, because their par ents have told them about it. I then explain to them that it is those memories that the liars are trying to destroy, and their new lies are intended for the next generation. Orwell called it falsification of the past, where the truth goes down the memory hole. I tell them thats the meaning behind the 1984 quote: Who controls the past, controls the future: who controls the present, controls the past.As the conversation comes to a close, one thing we always agree on, is that the people who slaughtered JFK were evil. And the enemy of evil is good. Kennedy opposed evil, therefore Kennedy was good. Thats why they killed him. And then they killed his brother. And then they took his son. .u33f3d78b9adb9eb6ce842e6f76603ed7 , .u33f3d78b9adb9eb6ce842e6f76603ed7 .postImageUrl , .u33f3d78b9adb9eb6ce842e6f76603ed7 .centered-text-area { min-height: 80px; position: relative; } .u33f3d78b9adb9eb6ce842e6f76603ed7 , .u33f3d78b9adb9eb6ce842e6f76603ed7:hover , .u33f3d78b9adb9eb6ce842e6f76603ed7:visited , .u33f3d78b9adb9eb6ce842e6f76603ed7:active { border:0!important; } .u33f3d78b9adb9eb6ce842e6f76603ed7 .clearfix:after { content: ""; display: table; clear: both; } .u33f3d78b9adb9eb6ce842e6f76603ed7 { display: block; transition: background-color 250ms; webkit-transition: background-color 250ms; width: 100%; opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #95A5A6; } .u33f3d78b9adb9eb6ce842e6f76603ed7:active , .u33f3d78b9adb9eb6ce842e6f76603ed7:hover { opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #2C3E50; } .u33f3d78b9adb9eb6ce842e6f76603ed7 .centered-text-area { width: 100%; position: relative ; } .u33f3d78b9adb9eb6ce842e6f76603ed7 .ctaText { border-bottom: 0 solid #fff; color: #2980B9; font-size: 16px; font-weight: bold; margin: 0; padding: 0; text-decoration: underline; } .u33f3d78b9adb9eb6ce842e6f76603ed7 .postTitle { color: #FFFFFF; font-size: 16px; font-weight: 600; margin: 0; padding: 0; width: 100%; } .u33f3d78b9adb9eb6ce842e6f76603ed7 .ctaButton { background-color: #7F8C8D!important; color: #2980B9; border: none; border-radius: 3px; box-shadow: none; font-size: 14px; font-weight: bold; line-height: 26px; moz-border-radius: 3px; text-align: center; text-decoration: none; text-shadow: none; width: 80px; min-height: 80px; background: url(https://artscolumbia.org/wp-content/plugins/intelly-related-posts/assets/images/simple-arrow.png)no-repeat; position: absolute; right: 0; top: 0; } .u33f3d78b9adb9eb6ce842e6f76603ed7:hover .ctaButton { background-color: #34495E!important; } .u33f3d78b9adb9eb6ce842e6f76603ed7 .centered-text { display: table; height: 80px; padding-left : 18px; top: 0; } .u33f3d78b9adb9eb6ce842e6f76603ed7 .u33f3d78b9adb9eb6ce842e6f76603ed7-content { display: table-cell; margin: 0; padding: 0; padding-right: 108px; position: relative; vertical-align: middle; width: 100%; } .u33f3d78b9adb9eb6ce842e6f76603ed7:after { content: ""; display: block; clear: both; } READ: Attempt at reconstruction EssayBut, as I say, dont believe me. Do your own research. Turn off the telescreen while you still can. Stop taking the soma of BRAVE NEW WORLD. Learn what Kennedy was up against before and during his administration. Learn what happened after his death. Soon a picture will begin to emerge, and the picture is not pretty. But it is accurately described by Orwell in 1984.
Friday, May 1, 2020
She Stoops to Conquer free essay sample
When they are done, the Landlord comes in and says there are two lost travelers outside looking for directions to get to Mr. Hardcastles residence. Tony tells the Landlord to send them in to him. Tony then tells his friends to go away so they will not ruin the joke he is planning. The Landlord shows Marlow and Hastings in and comments on how lost the two travelers are. Hastings reminds Marlow that if he had not been so shy they would have stopped for directions and arrived at their destination much sooner. Tony approaches Marlow and Hastings. He says that he has heard they are looking for Mr. Hardcastle. When they confirm his assumption, he gives them an artificially complicated set of directions. When Marlow and Hastings comment that it will be impossible to find the Act III Summary Act III is set solely in Hardcastles home. Hardcastle enters alone, confused over what his friend Charles Marlow meant by describing the young Marlow as modest, considering the young mans behavior thus far. We will write a custom essay sample on She Stoops to Conquer or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page Hardcastle is particularly worried that the behavior will put off his daughter. Kate enters, in a plain dress per her fathers wishes, and both express their shock at how different Marlow is from his or her expectations. Of course, Kate is confused over his modesty (expecting impudence), and Hardcastle over his impudence (expecting modesty). They realize the contradiction but Hardcastle does see they both know enough to reject him, a decision Kate approves unless she can reveal him to be more pleasing to each of them than they yet realize. Hardcastle finds such an outcome unlikely, but grants her license to attempt to correct his first impression, assuming her desire to do so is only because she thinks he is good-looking, and so wants to find something to like in his character. They leave, and Tony rushes on, holding the casket containing Constances jewels. Hastings joins him, and Tony reveals he has stolen the jewels, which concerns Hastings since he knows Constance is slowly finding success at convincing the old woman to turn over the jewels willfully. Tony calms him, assuring Hastings that he himself will take care of any resentment that might arise in Mrs. Hardcastle. They hear the women approaching, so Hastings exits quickly with the casket. Mrs. Hardcastle attempts to convince Constance that a young woman does not need jewels, which should be reserved to disguise her faded beauty when she gets older. Constance does not accept the argument, so Mrs. Hardcastle attempts to have Tony praise her beauty to dissuade her from pursuing the jewels. Tony pulls his mother aside, and suggests she lie to Constance, claiming the jewels have been stolen so as to put an end to the matter. Mrs. Hardcastle, who admits to him that she merely wants to save the jewels for him (and hence does she try to set them up in marriage), gladly accepts the plan. Mrs. Hardcastle makes a mock confession of the missing jewels, which Constance refuses to believe until Tony stands as witness to the lie, claiming he too has seen them missing. Constance is upset, and Mrs. Hardcastles offer to lend the girl her garnets does nothing to comfort her, but Mrs. Hardcastle nevertheless leaves to fetch them. While she is gone, Tony confesses his plan to Constance, who is happy. However, Mrs. Hardcastle returns quickly, having discovered the jewels have actually been stolen. She laments their loss dramatically, and Tony plays along, as though this is still their play-acting for Constances benefits. Her attempts to convince him the jewels are actually stolen (which he of course knows to be the case) only lead him to play-act harder, which makes her angrier until she charges offstage. All exit, and Kate enters with a maid, laughing about the joke Tony played on the men. The maid tells Kate that, as they passed Marlow moments before, he asked the maid about Kate, believing her to be a barmaid because of her simple dress, and because he was so shy with her before that he had never seen her face. Kate sees in this mistake an opportunity to deceive him, and decides to continue playing the barmaid so that she can glimpse his true character and so that she shall beà seen. The maid wonders whether Kate can pull off such a ruse, but Kate promises she has the required acting skills. Marlow enters, remarking to himself how terrible is his situation and how he will leave soon. Kate, acting the barmaid, approaches him and asks if she can help, offers he refuses until he notices her beauty. He grows immediately flirty and open, remarking on the nectar of her lips. They speak with great wit, and he confesses to his ability with ladies in town, speaking in lively tones of his life there. Kate asks whether he was so free when he spoke with Miss Hardcastle (which is of course herself, but he doesnt realize that), and he insists he is not in awe of her. Kate also says, in character, that she has lived in the house for 18 years. Overcome with passion, he pulls her close right as Mr. Hardcastle enters. Marlow quickly exits, and Hardcastle confronts Kate, accusing her of lying about Marlows modesty before since he just saw such an aggressive move. Kate asks for more time to reveal his true characterââ¬âhis virtues that will improve with age. Hardcastle denies her until she promises to prove her point by the end of the evening, a limit to which he agrees.
Saturday, March 21, 2020
Teacher Cadet free essay sample
Ever since I was younger, I possessed unique individual qualities. I was always the girl in class who always reminded the teacher about homework, the one who never missed an assignment, and the one who always made the honor roll. In fact, I never settled for mediocre because I knew one day it will pay off. Throughout my educational career, Iââ¬â¢ve learned that being yourself is the key to becoming successful. The world is filled with people attempting to duplicate someone which is why Iââ¬â¢ve always pushed myself to be unique. I devote much time in expressing my individual capabilities. Whether itââ¬â¢s singing on the choir or going more in depth into my spirituality; I always leave room for me. I am a firm believer in devoting my time to my individualism. When a person knows there inner-self and can come to turns with their problems, it shows a high level of maturity. We will write a custom essay sample on Teacher Cadet or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page For me, learning is the foundation for education. And without education there is just nothing to rely on. There is not a day that passes that I do not learn something new. Surrounding myself around a diverse group of people has a lot to do with as well. Over the past years, I have learned to value my diversity and how it affects my everyday life. For example, since enrolling in Teacher Cadet, I have learned so much about myself and peers that I probably would have never known until now. Iââ¬â¢ve also learned priceless values that helped shape me into the person I am today. In most cases, we do not consider that learning is necessary to move forward in life. Honestly, learning is my passion as a young adult. There is so much in the world that I am not aware of. So when someone enlightens me on unfamiliar topics, I immediately become intrigued and interested. In actuality, I enjoy learning new things from leaders and teachers who want to see me succeed in life. Leadership is attained by mutual cooperation between multiple parties. Usually, people who follow need inspiration so they will be able to eventually model the personââ¬â¢s behavior. Leading is not an easy task. It takes much patience, diligence and effort to fully lead a crowd of people. Throughout my day, I take the challenge as being the leader in many different things. For one, I am a squad leader in JROTC. That is a huge responsibility when you are in control of a lot of individuals. I believe responsibility and leadership are closely related because you cannot have one without the other. In my short career, I have accomplished many things. Iââ¬â¢ve been nominated for national society of high school scholars and received an invitation to theà People to People. Leadership Symposium. Without perseverance, I would not have been able to accomplish these things. I always strive to be the best and to the best. I love going the extra mile in everything I do. Many people do not enjoy volunteering in the community. Well, I love to volunteer my quality time to organizations in need. Being JROTC has sculpted me into a volunteer worker that actually enjoy helping people. You will be surprised the amount of help many organizations request. On many occasions, Iââ¬â¢ve volunteered at the Crisis Ministry of Charlotte. Assisting with folding, unpacking and stocking shelves were some of the few things I did. It was an amazing experience. I met a lot of people who were welcoming and assisted me with anything I needed. Ultimately, I enjoy being myself. Itââ¬â¢s what I do best. My success is not measured on how perfect I am but what I obtain in life. Although, I fall short of my goals every day, I still manage to keep going. Thereââ¬â¢s nothing worse than a person giving up on something they really want. When I decide to give up, thereââ¬â¢s always that voice in the back of my head that says ââ¬Å"Tytiana, Keep on keeping on.â⬠And of course I have no choice but to listen. Being a leader and a learner has changed my entire outlook and attitude toward life.
Thursday, March 5, 2020
Food, Eating and Drinking in Genesis essay
Food, Eating and Drinking in Genesis essay Food, Eating and Drinking in Genesis essay Food, Eating and Drinking in Genesis essayFood, eating and drinking have multiple implications in Genesis, which vary from the source of living granted for people by God to the subject of the seduction and downfall of humans, who have violated divine laws through eating the forbidden fruit.Initially, God provided food for humans and made them live a happy and careless life, as they were supposed to respect divine laws and live in the Eden, where they could rip fruits brought by the land and use them as food: ââ¬Å"I give you every seed-bearing plant on the face of the whole earth and every tree that has fruit with seed in it. They will be yours for foodâ⬠(Genesis 1: 29). Therefore, food was granted for people by God and they should just rip fruits and food from the land blessed by God.One of the turning point in the Genesis story is the story of seduction of Eve by the Serpent and Adam by Eve. Humans eat the forbidden fruit in the Eden. The act of eating the forbidden fruit sy mbolizes the violation of divine laws and rebellion of humans against God. The act of eating the fruit is the direct violation of Godââ¬â¢s ban to eat from the tree of knowledge. At the same time, the act of eating the forbidden fruit implies the intrinsic strife of humans for knowledge as well as the implicit sinfulness of humans, who cannot obey to strict divine laws but, instead, want to live their own life, even if it contradicts to the will of God.Thus, food, eating and drinking reveals the Godââ¬â¢s care for people and negligence of people with the divine will.
Tuesday, February 18, 2020
Development of International Business Essay Example | Topics and Well Written Essays - 1250 words
Development of International Business - Essay Example Also known as the Global Value Chain (GVC), it is a sophisticated model that shows how a firm retrieves raw materials, imbibes value to them through different processes and techniques and sell the final goods to consumers. There is slight distinction between GCC and GVC. GCC focuses on effective role of powerful retailers and branded merchandisers and GVC provides approaches to expand firm level research on the dynamics and strategies of global industries. Dicken (2015) observed that the Global Production Network (GPN) associates concentrated diffusion of the value chains beyond firms and nations with the process of accumulation of stratified layers of participants of the network. It is also known as Value Network, Input- Output Matrix. It is basically a collection of two or more value chains in which at least one network linkage is shared. According to Ernest and Kim (2001), the chief firm or flagships can be of two types; the first type of flagships constitutes the part of brand leaders that permits suppliers to be self-reliant but demand powerful performance from them. The second type consists of contract manufacturers which built their own production channels and create unified supply chain which are accessible to brand leaders. A GPN lead by firms can participate in different value chains. Hence, a global value chain can have two or more production networks. Solectron, a renowned international electronics manufacturing company, i s an example of GPN (Fleischmann and Koberstein, 2014). There is a wide difference in the terms of the two concepts. ââ¬ËChainââ¬â¢ identifies the vertical arrangement of acts that leads to maintenance, delivery and consumption of a distinct goods or services. ââ¬ËNetworkââ¬â¢, on the other hand, designs both the horizontal and vertical linkages between economics factors, i.e., identifying the common economics factors in the value chains which are effective. Gereffi and Korzeniewicz (1994)
Monday, February 3, 2020
PHL317Marx and Marxism Essay Example | Topics and Well Written Essays - 1250 words
PHL317Marx and Marxism - Essay Example Marx and Engels underline a leading role of the working class supposing that popular revolution could overthrow the repressive oligarchies of wealth and did not set them apart from the principles of democracy but, on the contrary, placed them squarely in the mainstream of the mid- nineteenth-century democratic tradition. "The proletarian movement is the self-conscious, independent movement of the immense majority in the interest of the immense majority." Thus they could make the equation that "to win the battle of democracy" would be the same thing as "to raise the proletariat to the position of ruling class." A "democratic constitution" would produce the "rule of the proletariat" (Marx and Engels 2006). Thus Communist Manifesto could assert even more plainly in a contemporaneous article that "a necessary consequence of democracy in all civilized countries is the political rule of the proletariat" (Marx and Engels 2006). Marx and Engels did indeed mistake the birth pangs of industria lism for the death throes of capitalism (Selsam and Martel 43). What is important for is that political strategy rested upon these expectations--however fanciful--of a geometrically multiplying proletariat and an impending economic cataclysm. First, the Manifesto asserted, when free competition is viewed as a process over time, the inevitable result is a concentration of ownership, with the less efficient enterprises going bankrupt or bought up by the more efficient. This law of concentration applies not only to industry but also to agriculture and distributive enterprises. Thus the manifold gradations of preindustrial society give way to a great gray mass of almost undifferentiated wage earners. This tendency of capitalism to replace skilled by unskilled labor is scarcely mentioned by Marx's followers nowadays-for obvious reasons--yet it clearly belonged to the original prognosis. These events lead to dissatisfaction of the working class and force them to oppose the regime. In this case, it becomes the first way of revolution and further class struggle (Szporluk 84). The idea that the working class leads the revolution is based on the concept of majority rule. Marx conceived that each successive class was "called to rule" and to emancipate mankind in some degree. During each period of emancipation, history awarded majority support, as it were, to this ruling class, because the masses would perceive the leadership of the chosen group genuinely to advance the interests of the whole society. So it had been in proper bourgeois revolutions, when the masses had provided the muscle for the bourgeoisie in its struggle to break out from the fetters of feudalism. So it would be again when the proletariat was called upon to play its ultimate emancipatory role, but not, perhaps, before the compass needle of universal suffrage registered "various deviations" (Szporluk 89). Among these, Marx also seemed to anticipate that the successful creation of a republic would dissolve the tripartite class alliance, leaving the more radical proletarian minority at first i n opposition to a "pale" democratic government representing the petty-bourgeois and peasant majority. He implied as much when differentiating himself politically from one of the leading "petty-bourgeois" democrats" The Communist Manifesto states: "The bourgeoisie cannot exist without constantly revolutionizing the
Sunday, January 26, 2020
Comparative Genomics Research Benefits
Comparative Genomics Research Benefits ABSTRACT The rapidly emerging field of comparative genomics has yielded dramatic results. Comparative genome analysis has become feasible with the availability of a number of completely sequenced genomes. Comparison of complete genomes between organisms allow for global views on genome evolution and the availability of many completely sequenced genomes increases the predictive power in deciphering the hidden information in genome design, function and evolution. Thus, comparison of human genes with genes from other genomes in a genomic landscape could help assign novel functions for un-annotated genes. Here, we discuss the recently used techniques for comparative genomics and their derived inferences in genome biology. INTRODUCTION Comparative genomics is the study of the relationship of genome structure and function across different biological species or strains. Comparative genomics is an attempt to take advantage of the information provided by the signatures of selection to understand the function and evolutionary processes that act on genomes. While it is still a young field, it holds great promise to yield insights into many aspects of the evolution of modern species. The sheer amount of information contained in modern genomes (750 megabytes in the case of humans) necessitates that the methods of comparative genomics are automated. Gene finding is an important application of comparative genomics, as is discovery of new, non-coding functional elements of the genome. Human FOXP2 gene and evolutionary conservation is shown in a multiple alignment (at bottom of figure) in this image from the UCSC Genome Browser. Note that conservation tends to cluster around coding regions (exons). Comparative genomics exploits both similarities and differences in the proteins, RNA, and regulatory regions of different organisms to infer how selection has acted upon these elements. Those elements that are responsible for similarities between different species should be conserved through time (stabilizing selection), while those elements responsible for differences among species should be divergent (positive selection). Finally, those elements that are unimportant to the evolutionary success of the organism will be unconserved (selection is neutral). SCOPE OF COMPARATIVE GENOMICS One of the important goals of the field is the identification of the mechanisms of eukaryotic genome evolution. It is however often complicated by the multiplicity of events that have taken place throughout the history of individual lineages, leaving only distorted and superimposed traces in the genome of each living organism. For this reason comparative genomics studies of small model organisms (for example yeast) are of great importance to advance our understanding of general mechanisms of evolution. Having come a long way from its initial use of finding functional proteins, comparative genomics is now concentrating on finding regulatory regions and siRNA molecules. Recently, it has been discovered that distantly related species often share long conserved stretches of DNA that do not appear to code for any protein. One such ultra-conserved region, that was stable from chicken to chimp has undergone a sudden burst of change in the human lineage, and is found to be active in the developing brain of the human embryo. Computational approaches to genome comparison have recently become a common research topic in computer science. A public collection of case studies and demonstrations is growing, ranging from whole genome comparisons to gene expression analysis. This has increased the introduction of different ideas, including concepts from systems and control, information theory, strings analysis and data mining. It is anticipated that computational approaches will become and remain a standard topic for research and teaching, while multiple courses will begin training students to be fluent in both topic. Chromosomes from two genomes are drawn: human chromosome 1 (drawn with a global zoom factor of 50x) and mouse chromosomes 1-19, X, and Y with mouse chromosome 3 drawn enlarged 10-fold. Syntenic regions between human chromosome 1 and the mouse genome are connected by coloured curves (A), whose geometry and properties can be adjusted dynamically. Thus, all syntenic relationships with mouse chromosome 4 are coloured in orange (B), and all relationships falling within the 80-90 Mb region on human chromosome 1 are coloured in blue (C). Other relationships with alignments larger than 5 kb are coloured dark in grey (D) and all others are shown in light grey. The lines are drawn layered with light grey lines below all others, then dark grey, then blue and then orange. Although approximately 44,000 syntenic relationships are drawn, the use of a selective colour scheme maintains legibility. The outer track (E) is a histogram of the log density of syntenic regions over 100 kb windows on human c hromosome GENOMES ARE MADE OF Although living creatures look and behave in many different ways, all of their genomes consist of DNA, the chemical chain that makes up the genes that code for thousands of different kinds of proteins. Precisely which protein is produced by a given gene is determined by the sequence in which four chemical building blocks adenine (A), thymine (T), cytosine (C) and guanine (G) are laid out along DNAs double-helix structure BENEFITS OF COMPARATIVE GENOMICS Using computer-based analysis to zero in on the genomic features that have been preserved in multiple organisms over millions of years, researchers will be able to pinpoint the signals that control gene function, which in turn should translate into innovative approaches for treating human disease and improving human health. In addition to its implications for human health and well-being, comparative genomics may benefit the animal world as well. As sequencing technology grows easier and less expensive, it will likely find wide applications in agriculture, biotechnology and zoology as a tool to tease apart the often-subtle differences among animal species. Such efforts might also possibly lead to the rearrangement of our understanding of some branches on the evolutionary tree, as well as point to new strategies for conserving rare and endangered species. Comparative Genomics Goals Complete the sequence of the roundworm C. elegans genome by 1998. Complete the sequence of the fruitfly Drosophila genome by 2002. Develop an integrated physical and genetic map for the mouse, generate additional mouse cDNA resources, and complete the sequence of the mouse genome by 2008. Identify other useful model organisms and support appropriate genomic studies. METHODLOGY Genome correspondence Genome correspondence, the method of determining the correct correspondence of chromosomal segments and functional elements across the species compared is the first step in comparative genomics. This involves determining orthologous (genes diverged after a speciation event) segments of DNA that descend from the same region in the common ancestor of the species compared, and paralogous (genes diverged after a duplication event) regions that arose by duplication events prior to the divergence of the species compared. The mapping of regions across two genomes can be one-to-one in absence of duplication events; one-tomany if a region has undergone duplication or loss in one of the species, or many-to-many if duplication/loss has occurred in both lineages. Fitch et al., developed a method called BBH (Best Bidirectional Hits), which identifies gene pairs that are best matches of each other as orthologous. Tatusov et al., further enhanced this method, which matches groups of genes to groups of genes. Understanding the ancestry of the functional elements compared is central to our understanding and applications of genome comparison. Most comparative methods have focused on one-to-one orthologous regions, but it is equally important to recognize which segments have undergone duplication events, and which segments were lost since the divergence of the species. Comparing segments that arose before the divergence of the species may result in the wrong interpretations of sequence conservation and divergence. Further, in the presence of gene duplication, some of the evolutionary constraints that a region is under are relieved, and uniform models of evolution no longer capture the underlying selection for these sites. Thus, our methods for determining gene correspondence should account for duplication and loss events, and ensure that the segments we compare are orthologous Applications Gene identification Once genome correspondence is established, comparative genomics can aid gene identification. Comparative genomics can recognize real genes based on their patterns of nucleotide conservation across evolutionary time. With the availability of genome-wide alignments across the genomes compared, the different ways by which sequences change in known genes and in intergenic regions can be analyzed. The alignments of known genes will reveal the conservation of the reading frame of protein translation. The genome of a species encodes genes and other functional elements, interspersed with non-functional nucleotides in a single uninterrupted string of DNA. Recognizing protein-coding genes typically relies on finding stretches of nucleotides free of stop codons (called Open Reading Frames, or ORFs) that are too long to have likely occurred by chance. Since stop codons occur at a frequency of roughly 1 in 20 in random sequence, ORFs of at least 60 amino acids will occur frequently by chance (5% under a simple Poisson model), and even ORFs of 150 amino acids will appear by chance in a large genome (0.05%). This poses a huge challenge for higher eukaryotes in which genes are typically broken into many, small exons (on average 125 nucleotides long for internal exons) in mammals. The basic problem is distinguishing real genes those ORFs encoding a translated protein product from spurious ORFs the remaining ORFs whose presence is simply due to chance. In mammalian genomes, estimates of h ypothetical genes have ranged from 28,000 to more than 120,000 genes. The internal coding exons were easily identified using Comparative analysis of human genome with mouse genome. Regulatory motif discovery Regulatory motifs are short DNA sequences about 6 to 15bp long that are used to control the expression of genes, dictating the conditions under which a gene will be turned on or off. Each motif is typically recognized by a specific DNA-binding protein called a transcription factor (TF). A transcription factor binds precise sites in the promoter region of target genes in a sequence-specific way, but this contact can tolerate some degree of sequence variation. Thus, different binding sites may contain slight variations of the same underlying motif, and the definition of a regulatory motif should capture these variations while remaining as specific as possible. Comparative genomics provides a powerful way to distinguish regulatory motifs from non-functional patterns based on their conservation. One such example is the identification of TF DNA-binding motif using comparative genomics and denovo motif. The regulatory motifs of the Human Promoters were identified by comparison with other m ammals.Yet another important finding is the gene and regulatory element by comparison of yeast species. Applications of comparative genomics to wheat A number of important major traits requiring elucidation in wheat are essentially non-polymorphic. Thus there is no prospect of creating a mapping population which is the starting point of all positional cloning strategies in most species to date. Moreover given the size of the wheat genome, many traits lie in regions where the gene density per BAC is one or two, making it difficult if not impossible to walk from one wheat BAC to the next. The Ph1 locus (controlling chromosome pairing in wheat) is one such example, in which the starting point was wild type wheat and a mutant carrying a deletion of more than 70Mb (almost the size of the whole Arabidopsis genome). Its phenotype is not easy to score. My group wished to characterise this locus. We created three different types of mutagenised populations, sequenced the equivalent rice Ph1 region, built BAC libraries (all are now available free of IP) for Brachypodium (a small genome species more closely related to wheat), sequenced Brachy podium Ph1 equivalent region, built a hexaploid (CS) (737,000 clones) wheat in collaboration with INRA (providing a further 500,000 clones), exploited Jorge Dubcovskys Tetraploid wheat BAC library, sequenced wheat BACs and defined the tissues in which the Ph1 phenotype is expressed. I will discuss the approaches adopted and resources created. Application of comparative genomics to the analysis of vertebrate regulatory elements Gene regulatory regions (also known as cis-regulatory modules) in vertebrates are poorly understood and annotated by comparison with protein-coding sequences. The short and degenerate sequences of regulatory elements and their distribution over large intergenic and intronic regions pose a major challenge to genomics scientists. Comparative genomics can be used to identify putative regulatory regions, and to analyse regulatory regions into their constituent transcription factor binding sites. There is need for high throughput assay systems to analyse the function of predicted vertebrate gene regulatory regions Other applications Comparative genomics has wide applications in the field of molecular medicine and molecular evolution. The most significant application of comparative genomics in molecular medicine is the identification of drug targets of many infectious diseases. For example, comparative analyses of fungal genomes have led to the identification of many putative targets for novel antifungal. This discovery can aid in target based drug design to cure fungal diseases in human. Comparative analysis of genomes of individuals with genetic disease against healthy individuals may reveal clues of eliminating that disease. Comparative genomics helps in selecting model organisms. A model system is a simple, idealized system that can be accessible and easily manipulated. For example, a comparison of the fruit fly genome with the human genome discovered that about 60 percent of genes are conserved between fly and human. Researchers have found that two-thirds of human genes known to be involved in cancer have counterparts in the fruit fly. Even more surprisingly, when scientists inserted a human gene associated with early-onset Parkinsons disease into fruit flies, they displayed symptoms similar to those seen in humans with the disorder, raising the possibility that the tiny insects could serve as a new model for testing therapies aimed at Parkinsons. Thus, comparative genomics may provide gene functional annotation. Gene finding is an important application of comparative genomics. Comparative genomics identify Synteny (genes present in the same order in the genomes) and hence reveal gene clusters. Comparative genomics also helps in the clustering of regulatory sites, which can help in the recognition of unknown regulatory regions in other genomes. The metabolic pathway regulation can also be recognized by means of comparative genomics of a species. Dmitry and colleagues have identified the regulons of methionine metabolism in gram-positive bacteria using comparative genomics analysis. Similarly Kai Tan and colleagues have identified regulatory networks of H. influenzae by comparing its genome with that of E. coli. The adaptive properties of organisms like evolution of sex, gene silencing can also be correlated to genome sequence by comparative genomics. CONCLUSION The most unexpected finding in comparing the mouse and human genomes lies in the similarities between junk DNA, mostly retro-transposons, (transposons copied from mRNA by reverse transcriptase) in the two species. A survey of the location of retrotransposon DNA in both species shows that it has independently ended up in comparable regions of the genome. Thus junk DNA may have more of a function than was previously assumed. High performance computing tools help in comparing huge genomes. Because of its wide applications and feasibility, automation of comparing genomics is possible. Such Comparisons can aid in predicting the function of numerous hypothetical proteins. REFERENCES en.wikipedia.org/wiki/Comparative genomics www.ncbi.nlm.nih.gov www.springer.com
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