Facts of the Matter
Facts of the Matter
Unraveling the mystery
of the human genome
is only beginningMapping the human genome was a gargantuan effort, but that decade-long project was the easy part, and only the beginning of the understanding that has the potential to lead to practically unimaginable applications.
The genome contains the recipe for making all the proteins made by the human body, and at one time it was thought that knowing the genome would lead to understanding of the proteins they code for. As it turns out there is much more to it than this; merely knowing the alphabet doesn't mean you can read and write.
The human genome contains approximately three billion letters, or DNA base pairs, which translates into roughly 40,000 genes. Any one cell makes hundreds of thousands of distinct proteins, and in the human body overall, there are roughly half a million different proteins. These proteins differ slightly from one individual to another, which is part of what makes us individuals, why some of us are allergic to certain foods, or are more susceptible to certain diseases than other people.
Proteins are the fundamental chemicals of life. They are the bricks and mortar of cells and of virtually all body tissue, from hair and nails to skin and bones, teeth, enzymes, hormones, blood, antibodies, organs and muscles. Networks of proteins form the structure of the body, and the types of proteins and the way they are networked distinguishes the various types of cells. Although all cells have the same genome, cells of different types differ in which genes are active and therefore differ in which proteins they make.
Proteomics is a general term used for the study of proteins. It consists of three distinct but related areas of research: identifying all the proteins made in a cell, tissue or organism, determining the nature and structure of protein networks, and outlining the precise three-dimensional structure of proteins in order to find where drugs might turn their activity on or off.
Genes code for the production of proteins by lining up amino acids, dictating which amino acids should be strung together. But merely knowing the amino acid sequence of a protein does not specify what the protein does, how it is shaped or which other proteins it engages with.
No one knows for sure how a cell "knows" which protein to make and when.
For example, diseased cells may produce proteins that healthy cells don't, and vice versa.
Even worse, many variables, such as whether someone has just had a glass of wine, can affect the type of proteins the body produces.
One of the lessons learned from the genome project is that the old dogma of one gene coding for one protein is just not true. As it turns out, one gene can somehow give rise to many different proteins.
Another complication is that the geometry of proteins gives them many of their properties. Proteins form intricate networks, and once the amino acids are strung together, the proteins bend and fold into complex shapes.
Additionally, cells modify their proteins by adding sugars and fats, so merely stringing amino acids together, even in the correct sequence, will not ensure that the proper modifications are made.
In many cases, such as with enzymes, a protein fits into other molecules like a key into a lock, holding them close to facilitate chemical reactions, or keeping them apart to slow or prevent reactions from taking place.
Although there are techniques for determining the shape of existing proteins, it is a long and expensive process, and not one-hundred percent accurate. There is no sure way to predict the shape of a particular protein from the genome, even if the sequence of amino acids is known precisely. Predicting the shape of the proteins that are formed is a mystery, for now.
To understand what proteins do in the body and to develop useful drugs, it is necessary to know how the mix of proteins varies from one cell type to another and within a cell as conditions change; equally important is to know how proteins collaborate to carry out a cell's various activities and how the shapes of proteins enter into it.
There is much active proteomics research to unravel the "proteome," with hopes for providing answers to many diseases such as cancer, diabetes, and hundreds of others that are influenced by genetics in one way or another.
Proteins are the most important of all biochemicals, involved as they are in nearly all bodily processes in one way or another. Understanding the shapes and how the sequence of amino acids determines the shape is the central problem -- the most pressing and most intriguing one in biochemistry.
We could all be a little smarter, no? Richard Brill picks up
where your high school science teacher left off. He is a professor of science
at Honolulu Community College, where he teaches earth and physical
science and investigates life and the universe.
He can be contacted by e-mail at rickb@hcc.hawaii.edu