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

Cultural Profile of the Philippines Essay

The Philippines is a country with diverse culture. The country is divided into regions and provinces wherein each region or province has distinct cultures of their own. Greatly influenced by the Spanish colonization in the 14th to 18th century, the country has a lot of colorful festivals that showcase that the cultures and products of the regions. Part of the Filipinos’ diverse culture is their languages. Officially, Filipino and English are the major languages. Filipino is a compendium of more than 180 dialects but most of the words are based on Tagalog, the lingua franca of the National Capital Region, the seat of the government. Majority of Filipinos speak eight major dialects namely Tagalog, Cebuano, Ilocano, Hiligaynon or Ilonggo, Bicol, Waray, Pampango and Pangasinense. English, on the other hand, is used as a medium of instruction in many educational institutions and as language in documents of the government (â€Å"About the Philippines†). Impact on Business Communication Because the Philippines has been colonized by many nationalities, it has adopted a lot of cultures. With that, Filipinos become flexible in dealing with other people with other cultures and social backgrounds. Moreover, they have the willingness to learn especially that labor has been one the major exports of the country. Many Filipinos are becoming competitive in the global market and business. In terms of relationships, Filipinos possess strong interpersonal relationships that make it more advisable for them to be introduced first to a third party than having them introducing themselves. However, Filipinos value relationships so much be it with their families of relatives or even in business. They do not focus only to business but they make ways in knowing their business partners deeper even to their personal affairs. They believe that when they know the people they are dealing with; it is easier for them to communicate their ideas for the business. They value their relationships not only for the present business deals but also for the future. They are used to referring people they know to be employees in their businesses (â€Å"Philippines — Language, Culture, Customs, and Etiquette†). In business, they also make sure that they are presentable at all times and they prefer face-to-face meeting from making phone calls or email; that is one way they can build relationships to people and business colleagues. Since they are relational, sometimes they are more particular with the personalities rather than the company they represent (â€Å"Philippines — Language, Culture, Customs, and Etiquette†). In the global business, the flexibility, adoptability and professionalism of Filipinos could be advantages especially about their being relational. They will open more areas of communication among their fellow employees and to other people outside the company which they believe can help them in their work. Also, they can easily learn other languages that may be required in doing business because their culture has already thought their tongues to be more adoptive to environments. References Kwintessential Cross Cultural Solutions. (______. ) Philippines — Language, Culture, Customs, and Etiquette. Retrieved May 14, 2008 from http://www. kwintessential. co. uk/resources/global-etiquette/philippines-country-profile. html Wow Philippines. (______. ) About the Philippines. Retrieved May 14, 2008 from http://www. tourism. gov. ph/discover/h

What Needs to be Done About Good Nonfiction Essay Topics Before It Is Too Late

What Needs to be Done About Good Nonfiction Essay Topics Before It Is Too Late A specific use of terminology is critical in a text which should be educational. The lexical structure of your very own specialized file has to be correct and totally free of all sorts of ambiguities. Finding a new domain no longer needs to have a lot of time! Transferring a domain tends to have a very long time, an extremely long time actually. 1 mistake many IELTS pupils do make is to select the test, with no comprehension of how the check functions. Teachers also needs to supply the youngsters suitable instructions for every type of composition that they need to compose. Teens ought to be able to pick their bedtime. Ally you must do is to correctly submit your order instructions and create the payment. If you want to help your son or daughter understand how causal relationships work, you can discover some handy cause and effect worksheets here. It is worth it to read superior magazines. For beginners, it is best to try out both to be in a better position to generate an educated selection. Say you want to enrich your writing abilities to make certain that you may possibly send business e mails. Shakespearean materials found recognition within this age. Argumentative essay topics are so important since they are debatableand it's important to at all times be critically considering the world around us. Since you may see, the topics are split between multiple categories so it would be simpler that you select one. You can begin with the kind of topic you pick for your compare and contrast essay. Researching the topic will permit you to find out more about what fascinates you, and should you pick something you truly like, writing the essay will be more enjoyable. Let's shake this up already! Superior world war two research paper topics. Persuasive essay standpoint. Yes, there's a person who can aid you with your essays expert essay writers at MyPerfectWords. Moral argumentative essay topics are a few of the simplest to get carried away with. Narrative essays serve a broad range of purposes. Inside my experience, descriptive essays are only difficult in regards to deciding just what things to write about. In the following article, you will discover lots of helpful suggestions about how to compose a creative essay you may use whenever making your very own intriguing stories and articles. You are able to interest books, movies or articles which are discussing exactly the same topic you're likely to approach in your essay. This informative article puts more focus on subjects and topic for these kinds of essays since without a great subject, you might wind up getting stuck and need to start over and over again. Some authors point with a summary of love. The above mentioned compare and contrast essay topics are only a few of many topics you are able to decide to go over in your essay. The very first thing you ought to do is identify the form of compare and contrast essay which you are handling. In most instances, the topics you select should be closely related. Lucky for you, there are a lot of topics you could concentrate on when writing and it's all your responsibility to figure out the precise topic that you wish to build on. Good Nonfiction Essay Topics - What Is It? Year round school isn't a good idea. Think about a great title for your undertaking. Egg laying business program. Business plan associated with biotechnology. When you're prepared to think of a thesis, take a look at these Argumentative Thesis Statement Examples. Normally, the teachers or professors assign the topics by themselves. School tests aren't powerful. The IELTS test was made to look at your capacity to convey in English, therefore finally you're not able to score nicely without a massive level of Language.

Instantiation and the Initialize Method