Brain Candy: Biochemical LEGO Blocks
Biochemical LEGO Blocks
Life would be so much easier if we could just look at the source code. —Dave Olson
Magic Stuff
Just about all of the ``stuff'' in your body is made from proteins. Proteins, in turn, are made up of long strands of amino acids. Since there are only 20 amino acids, and since proteins can be used for so many useful things (like muscle, eyeballs, and bones), amino acids are a lot like the LEGO blocks of the biochemical world.
The discovery of how DNA encodes proteins is right up there in importance (at least in my mind) with the discovery of fire and the invention of the wheel. However, there are easily far more unanswered questions about biochemistry than answers. In fact, when the human genome project is finished in a couple of years, we may have enough research problems to last another century or more.
In this column, we will take a whirlwind tour through the process of genetic decoding. Along the way, I'll highlight some strange facts about biochemistry. At the end, we'll touch base on one of the best kept secrets of 1995: an adult human was cloned.
On Legos and Language
DNA is made from a chain of four chemical bases that can be represented by the letters A, C, G, and T (the letters are shorthand for the chemical names of the bases - adenine, guanine, cytosine, and thymine). Each base has a complement that it pairs up with (A with T and C with G), which means that every sequence of bases has a mirror version, for instance, ``CATTAG'' complements ``GTAATC'' and vice versa. The famed double helix of DNA consists of two long, intertwining strings of these letters, each a mirror of the other.
| DNA | Long strand of four base pairs: A, C, G, and T. |
| Gene | A contiguous segment of DNA that codes a protein. |
| Amino Acid | Comes in twenty varieties. Each corresponds to one or more base triplets. |
| Protein | A long strand of amino acids. Used as building material and for regulating biochemical reactions. |
Table 1. A Rossetta Stone of biochemistry.
The four base letters can be used to compose ``words'' inside of cells. We know that this language has exactly twenty words plus a couple of ``punctuation marks'' (i.e., DNA segments that mean ``this is the end of a sentence.'') A word is specified by three letters and corresponds to one of twenty amino acids. Extending the analogy, since a protein consists of many words, we can think of a protein as a long sentence or a paragraph. The mapping from base triplets to amino acids is the gist of the genetic code.
Weird Fact #1: The mapping from base triplets to amino acids is redundant because three bases can encode up to 64 different words. Moreover, this mapping could have been different. If DNA-based life is ever discovered elsewhere, it will probably use a very different mapping.
Table 1 contains a list of the basic building blocks of life, and describes how each related to the others. While recipes are handy things for chefs, the best recipe in the world is useless unless you have the right ingredients and the proper gizmos to do the job. To make use of DNA, cells need tools that ``understand'' the language of DNA. This is where RNA comes into the picture.
Figure 1. Gene expression in three stages: (1) the information encoded in DNA is copied to a strand of messenger RNA (mRNA) which (2) moves outside of the nucleus and eventually to a ribosome where (3) transfer RNA (tRNA) combines with the mRNA to assemble a protein.
Figure 1 illustrates the process by which protein is fabricated inside of a cell. It begins inside of a cell nucleus, where the double helix of DNA is pulled apart like a zipper. Messenger RNA (denoted mRNA) can then match up to a strand of the DNA so that a copy of the information can be safely transported outside of the cell. Once the mRNA travels through the cell's cytoplasm, it can then hookup with a ribosome, which takes care of the remainder of the protein making process.
Out in the cell cytoplasm, transfer RNA (tRNA) binds to free amino acids that are floating about. Each tRNA molecule binds to one type of amino acid and matches a specific three base sequence. The tRNA rendezvous with the mRNA in the ribosomes, where a protein chain is progressively assembled so that each amino acid in the chain matches a base triplet that appears in the DNA.
Weird Fact #2: Proteins can vary in many insignificant ways. Among humans, there are hundreds of variations of hemoglobin. However, hemoglobin in other animals can vary by as much as 50%, yet still perform the same basic function (transporting oxygen).
When Function Follows Form
Different amino acids behave in different ways when exposed to water. Some amino acids are attracted to water, some are repelled by it, and others are more or less neutral. In the aqueous interior of cells, proteins chains will twist, turn, fold, and contort so that the water-liking amino acids are exposed to the surface and the water-hating amino acids are trapped in the interior. This forces the linear chain to assume a three-dimensional shape, and it is this 3D shape that gives a protein it's chemical properties.
Understanding protein folding is one of the great open challenges of molecular biology. Currently, there is no general technique that can accurately predict what the 3D structure of a protein will look like just by examining the amino acid sequence that defines it. The problem is so complex that all current computer simulations of the problem are painfully slow and woefully inaccurate.
Context Sensitivity
Enzymes are proteins that are responsible for regulating biochemical reactions inside of cells. At any given time, a cell utilizes thousands of proteins at once to keep things going. However, most multicellular animals have many different cell types, and each of these cell types will have a different set of genes that are active.
How, then, do cells know which proteins to make? The answer, oddly enough, is that the current composition of a cell's chemical soup determines what genes are later expressed. Thus, a neuron ``knows'' it is supposed to be a neuron because its internal chemistry says as much. This means that to a certain extent, the protoplasm of a cell controls the nucleus, and the nucleus controls the protoplasm.
External chemical imbalances can also result in profound differences in gene expression. For example, hormone imbalance during pregnancy can result in infants that are physically one gender, but genetically another. This example just goes to show that the instructions in DNA do not always reign supreme.
Weird Fact #3: Humans and chimpanzees are 97% identical, genetically. Just considering structural proteins, we are 99% identical. Thus, most of the differences are in regulatory genes, which is to say, we are made of the same stuff, but just assembled differently.
Weird Science
In 1995, the DNA from Dr. Jose Cibelli, of Advance Cell Technology, was implanted into a cow's egg. The egg divided into 32 stem cells and was then destroyed. The story of this event hit the news three years later. However, every major news outlet missed the point: this story is bigger than Dolly the clone by orders of magnitude. Not only was human DNA cloned, but a human/cow hybrid existed for a short time.
Ironically, why such a creature was produced may have had more to do with politics than with science. Prohibitions on human fetal tissue experimentation has been cited as justification for producing trans-genetic animals.
No one really knows how such a hybrid would develop had cell division been allowed to continue. Given the differences between cow and human DNA, many experts believe that no viable organism would have developed. But suppose a chimpanzee egg was used instead. Since chimps and humans are so genetically similar, some biologists have speculated that a chimp egg / human nucleus combination would result in a human. But it may also be possible for this type of hybrid to produce an animal that looks like a chimp, but contains nothing but human nuclei; in other words, a chimp made from human proteins.