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Genomics and Proteomics

By Namrata S. Patil, Ph.D. Medical Contributor

These are the new buzzwords in the biotech industry right now. What do they mean? Most of us have heard of genomics or the characterization of the complete set of genes in an organism and of the human genome project. The human genome project essentially mines the sequence of the all the DNA in human cells. DNA or deoxyribonucleic acid is found in every cell and is composed of a double-stranded string of four bases or units-adenine, guanine, cytosine and thymidine. As the DNA is sequenced, the order of the bases is revealed, for instance ATGGGCCTT. A string of about 1000-5000 such bases codes for one gene. The human genome has over 3 billion bases that codes for an estimated 50,000-100,000 genes. All of us have heard of genes, the genetic elements that control various physical traits, from eye color, height and skin color to traits that confer susceptibility to high blood pressure or diabetes etc. If you do the math and are wondering about the extra DNA apart from the genes, there is also a lot of 'stuffer' DNA in the human genome. It is believed to be involved in regulating when and where specific genes will get expressed. For instance, during development of the fetus, very specific genes are turned on one after the other to ensure the correct fetal development, from those involved in beating of the heart beginning at weeks 5-6, to formation of the early limb buds at week 7 etc. To look at the how this gene or specific DNA sequence gives rise to the actual physical trait, we need to look within the cell. In each cell, a gene gets transcribed into a message that is made of RNA or ribonucleic acid. This messenger RNA (mRNA) is a string made of adenine, guanine, cytosine and uracil instead of thymine of DNA and is typically single-stranded. The mRNA then gets translated to form a protein. A protein is made up of a string of 20 kinds of amino acids. You have probably heard of essential amino acids as dietary supplements. The body can make most of these amino acids, the ones it can't are termed essential, ie. one is dependent on the diet for these. Remember the dietary supplement for one of the essential amino acid lysine in Jurassic park? Going on with story in the cell, a set of three bases, called a codon, encodes for one amino acid. For instance AAA or AAG codes for lysine. These amino acids are joined together to form a protein as the cell machinery reads the messenger RNA. In the simplest scenario, one gene transcribes one message that is translated into one protein. This scenario allows predicting the sequence of the protein fairly accurately, with good software, if the sequence of the gene (DNA) is known. In reality however, one gene can code for multiple messages by the mRNA being spliced or altered after transcription, which in turn can translate into multiple proteins. Then there are some genes that are never transcribed or some messages that are never translated. Further, after being synthesized the protein can be modified biochemically in the cell, and these modifications can drastically change the function of the protein in the cell. Several proteins are required for a cell to survive and reproduce, to generate energy and synthesize essential molecules. Enter proteomics, the way to characterize a complete profile of proteins present in a given cell or biological system. Proteomics is essentially functional genomics in

that it sorts gene products or proteins, into families related by function, rather than DNA sequence similarity. Biologically, this makes a lot more sense since the proteins for each process in the cell are frequently quite unrelated, as are the DNA sequences of the genes that encode them, and so the link between them cannot be found by searching for DNA sequence similarities. Thus, though genomics is very useful, it cannot always predict what gene product or protein may be really important for a particular process in the cell or a disease. Finally since most drugs typically target proteins, that is where the proteomic companies make their grand entrance. To date, the limitations of proteomic companies are mostly technical, since proteins are much harder to analyze than nucleic acids. But since that is where the real action takes place, that is where the real disease mechanisms and potential cures will be discovered!

Genomics is sequencing the entire DNA in the cell to be able to predict the message and proteins that will be expressed Proteomics is identifying all the proteins in the cell to be able to discover their function in cell processes and disease