Genome Sequencing and Comparative Genomics Term Paper

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Genomes and Comparative Genomics

Over the last decade we have achieved rapid strides in the field of genetic engineering. The study of molecular biology has been fairly advanced mainly aided by the unprecedented growth in information technology. Today bio-informatics has opened new vitas for us and we are already progressing in investigating and in the comparative study of genomes. This has shed new light up on our knowledge of the evolutionary process and the important concepts such as protein folding and selective expression, which have so far eluded our understanding, are beginning to unfold. Let us have a brief overlook of the subject.

The Role of DNA

One of the greatest achievements of the twentieth century has been the unraveling of the mysteries behind the DNA and the mechanism of protein synthesis. Genes are the fundamental units of biological inheritance and are made up of Deoxyribonucleic acid (DNA). Genes are responsible for the manufacture of proteins that direct the different bodily functions. This idea of the important role of DNA in protein synthesis opened new possibilities in the sense that, by way of artificial insertion of DNA material, it is possible to stimulate the synthesis of the required protein. One of the complex and at same time most elegant aspects of our lives is the process by which instructions pertaining to protein synthesis is encoded in the DNA and the perfect manner in which the cytoplasmic components interpret them and assemble the proteins. The important point is that the order of assembling the amino acids (in the process of protein synthesis) is dictated by the order of the bases (ATCG) for that particular gene.

Scientists refer to the whole process of issuing instruction and protein synthesis as transcription and translation. The instructions in the DNA are first transcribed and then translated or converted into proteins. The procedure is a follows. The DNA instructions are transcribed into another molecule called mRNA, which is actually a copy of the DNA. The next step is the translating of the instructions in the mRNA molecule into protein form. mRNA instructions are actually in the form of words, which consist of groups of three bases called as codon. These codons in turn direct the cellular machinery in the assembling the protein. (Adding amino acids at the appropriate place).

The study of mRNA molecules holds the key to understanding the process of gene expression. The expression of a gene depends on the presence of the mRNA molecule within the cell. Whenever a particular protein is in demand the gene constructs a mRNA molecule. The mRNA molecule can be separated from the other constituents of the cell by centrifuging process. Today genetic engineers are able to isolate mRNA molecules that contain the genetic information for the synthesis of the protein molecule. These mRNA molecules can then be transferred to the specific DNA sequence.

This process has proved to be a huge bottleneck for researchers involved in genetic engineering. But soon it was found that the difficulties associated with transferring the mRNA back into the DNA sequence could be overcome by using enzymes. The process first identified in viruses involved the use of enzymes that convert mRNA into DNA. These enzymes are called as reverse transcriptases because they reverse the process of transcribing DNA into mRNA. Thus by adding reverse transcriptase enzymes to mRNA strands we will be able to create DNA strands. There are some other enzymes like the DNA polymerase that are used to convert the single strand DNA to its original double helical structure. So the process of synthesizing complementary DNA (cDNA an exact replica of the mRNAs) has become much easier. [G.R Chhatwal, 86]

History of DNA Sequencing

Fredrick Sanger was the first person to develop a satisfactory DNA sequencing technique. Sanger's technique was based on copying the DNA strands using deoxyribonucleic acid triphosphates and terminating the strands with dideoxyribonucleic acid triphosphates. Then using x-rays he was able to arrive at the location of the nucleotides bonds within the strands. However the process was highly cumbersome and time consuming one taking years together to complete the sequencing process. Sanger used his technique and successfully sequenced bacteriophage PX174 in 1977(REF) and in sequencing bacteriophage Lambda in 1982. The first complete genome to be sequenced was the human mitochondria genome in 1981. However Fleischmann and his group hold the credit for the first ever sequencing of a living organism when they successfully sequenced the DNA of Haemophilus influenzae in 1995. Scientists have been successful in sequencing more than a hundred different organisms and research is further proceeding with already a great amount of work done in arriving at the human genome.

Over the years Sanger's method was greatly simplified using fluorescent tags to the dideoxyribonucleic acid triphosphates and using laser beam to identify them. The DNA sequencing techniques have evolved a long way from the manual, labor-intensive methods to using the highly sophisticated modern techniques. However a remarkable breakthrough in Gene sequencing was achieved in 1983 when Kary Mullis the American researcher found out the polymerize chain reaction method. [Mullis, KB] There were many refinements made to these techniques and the time consumed for DNA sequencing was significantly reduced. Another major breakthrough in the sequencing technique was the 'short-gun' method devised by Craig Venter in 1991. This was an entirely different concept based on breaking down the DNA strand into thousands of smaller strands, which can be decoded using separate machines and finally reassembled. The correctness of this method is attested by the fact that the human genome project, which is currently underway, employs the 'short gun' method of DNA sequencing.

Sequencing Genomes (The applications)

There are immense applications for the genome-sequencing program. Once a complete genome is arrived at, the information can be used for improving our understanding and knowledge about any species. Right from improving our understanding of the phylogenetic relationships, which explain relationships between different species to developing efficient molecular treatment for life threatening diseases and extensive use in the field of forensic science the list of potential applications is seemingly endless.

Medical Applications

The field of molecular medicine will gain a new impetus with the completion of human genome project. Soon it will be possible for us to identify disease causes at the very basic level and respond with suitable treatments. Having the genome available would greatly accelerate our understanding of the specific genes that are responsible for hereditary diseases. Once this is identified scientists can consider gene therapy wherein the disease-causing gene can be replaced by the healthy gene. Genetic disorders will no longer be untreatable and gene therapy will mark an entirely new level of medical treatment. Another important application would be faster and easier management of organ or tissue transplants. With the genome information available organ transplants can be decided instantly. [Office of Science]

Agricultural Applications

Already we are hearing about genetically modified foods. The knowledge of Plant genomes provides us with the power to manipulate them in such a way so as to maximize the yield and minimize the loss. Scientists have succeeded in growing insect resistant and high yielding crops. With proper application of genetic engineering in the near future we can expect to generate huge yield without ever having to use harmful pesticides.

Forensic Science

The field of forensic science is already benefiting from the availability of DNA sequencing techniques. Today forensic experts are able to solve crimes with very little information that they have using the DNA fingerprint. Just like ordinary fingerprint analysis forensic experts would be able to tap the possibility of DNA sequencing for identifying culprits. This is already a reality and in the near future we can expect crime solving to be a lot easier and accurate with the availability of faster DNA sequencing techniques. [Office of Science]

Comparative Genomics

The study of genomes of different species would present us with a better picture as to the evolutionary trends, bioarcheology and anthropology. Researchers have identified that 99.9% of the genome information is common for the different human races stressing once again the possibility of a common ancestral origin. In the same vein they have also found that the chimpanzees have about 98.4% of genetic information common with humans. [Hecht, J] So the improvements in genome science is helping us ascertain our evolutionary trends better than ever before. Similarly mouse and human beings are found to share 97.5% of the DNA material implicating a common ancestral origin some hundred million years ago. [Cohlan, A]

Presently software programs are available which can expedite the comparison of genomes of different species. By means of comparing it is possible to identify the exact function of each gene as well as the purpose of the non-coding regions within a gene. Furthermore comparative study of genomes has confirmed the existence of gene duplications within different species. These genes may either be active or passive within the particular species and hence by means of a comparative study of the genes we may be able to better identify the selective…

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