How DNA Works

DNA is one of the nucleic acids, information-containing molecules in the cell (ribonucleic acid, or RNA, is the other nucleic acid). DNA is found in the nucleus of every human cell. The information in DNA:

The key to all of these functions is found in the molecular structure of DNA, as described by Watson and Crick.

Although it may look complicated, the DNA in a cell is just a pattern made up of four different parts called nucleotides. Imagine a set of blocks that has only four shapes, or an alphabet that has only four letters. DNA is a long string of these blocks or letters. Each nucleotide consists of a sugar (deoxyribose) bound on one side to a phosphate group and bound on the other side to a nitrogenous base.

There are two classes of nitrogen bases called purines (double-ringed structures) and pyrimidines (single-ringed structures). The four bases in DNA's alphabet are:

Watson and Crick discovered that DNA had two sides or strands, and that these strands were twisted together like a twisted ladder — the double helix. The sides of the ladder comprise the sugar-phosphate portions of adjacent nucleotides bonded together.

The phosphate of one nucleotide is covalently bound (a bond in which one or more pairs of electrons are shared by two atoms) to the sugar of the next nucleotide. The hydrogen bonds between phosphates cause the DNA strand to twist. The nitrogenous bases point inward on the ladder and form pairs with bases on the other side, like rungs. Each base pair is formed from two complementary nucleotides (purine with pyrimidine) bound together by hydrogen bonds. The base pairs in DNA are adenine with thymine and cytosine with guanine.

DNA is a long molecule. For example, a typical bacterium, like E. coli, has one DNA molecule with about 3,000 genes. If drawn out, this DNA molecule would be about 1 millimeter long. However, a typical E. coli is only 3 microns long (3 one-thousandths of a millimeter). So to fit inside the cell, the DNA is highly coiled and twisted into one circular chromosome.

Complex organisms, like plants and animals, have 50,000 to 100,000 genes on many different chromosomes (most humans have 46 chromosomes). In the cells of these organisms, the DNA is twisted around bead-like proteins called histones. The histones are also coiled tightly to form chromosomes, which are in the nucleus of the cell.

When a cell reproduces, the chromosomes (DNA) get copied and distributed to each offspring or daughter cell. Non-sex cells have two copies of each chromosome that get copied and each daughter cell receives two copies (mitosis). During meiosis, precursor cells have two copies of each chromosome that gets copied and distributed equally to four sex cells. The sex cells (sperm and egg) have only one copy of each chromosome. When sperm and egg unite in fertilization, the offspring have two copies of each chromosome.

DNA carries the information for making all the cell's proteins. These proteins implement all the functions of a living organism and determine the organism's characteristics. When the cell reproduces, it must pass all of this information on to the daughter cells.

Before a cell can reproduce, it must first replicate — or make a copy of — its DNA. Where DNA replication occurs depends upon whether the cell is a prokaryote or a eukaryote. DNA replication occurs in the cytoplasm of prokaryotes and in the nucleus of eukaryotes. Regardless of where DNA replication occurs, the basic process is the same.

The structure of DNA lends itself easily to DNA replication. Each side of the double helix runs in opposite (antiparallel) directions. The beauty of this structure is that it can unzip down the middle and each side can serve as a pattern or template for the other side (called semi-conservative replication). However, DNA does not unzip entirely. It unzips in a small area called a replication fork, which then moves down the entire length of the molecule.

Let's look at the details:

Different types of cells replicate their DNA at different rates. Some cells constantly divide, like those in your hair and fingernails and bone marrow cells. Other cells go through several rounds of cell division and stop (including specialized cells, like those in your brain, muscles and heart). Finally, some cells stop dividing, but can be induced to divide to repair injury (such as skin cells and liver cells). In cells that do not constantly divide, the cues for DNA replication/cell division come in the form of chemicals. These chemicals can come from other parts of the body (hormones) or from the environment.

DNA carries all the information for your physical characteristics, which are essentially determined by proteins. DNA contains the instructions for making a protein. In DNA, each protein is encoded by a gene (a specific sequence of DNA nucleotides that specify how a single protein is to be made). Specifically, the order of nucleotides within a gene specifies the order and types of amino acids that must be put together to make a protein.

A protein is made of a long chain of chemicals called amino acids. There are various types of proteins with different functions:

The particular sequence of amino acids in the chain is what makes one protein different from another. This sequence is encoded in the DNA where one gene encodes for one protein.

How does DNA encode the information for a protein? There are only four DNA bases, but there are 20 amino acids that can be used for proteins. So, groups of three nucleotides form a codon that specifies which of the 20 amino acids goes into the protein. A 3-base codon yields 64 possible patterns (4*4*4), which is more than enough to specify 20 amino acids.

Because there are 64 possible codons and only 20 amino acids, there is some repetition in the genetic code. Also, the order of codons in the gene specifies the order of amino acids in the protein. It may require anywhere from 100 to 1,000 codons (300 to 2,000 nucleotides) to specify a given protein. Each gene also has codons to designate the beginning (start codon) and end (stop codon) of the gene.

Building proteins is very much like building a house:

Let's look at each phase of the new construction more closely.

In a eukaryote, DNA never leaves the nucleus, so its information must be copied. This copying process is called transcription and the copy is mRNA. Transcription takes place in the cytoplasm (prokaryote) or in the nucleus (eukaryote). The transcription is performed by an enzyme called RNA polymerase.

To make mRNA, RNA polymerase:

mRNA is happy to live in a single-stranded state (as opposed to DNA's desire to form complementary double-stranded helixes). In prokaryotes, all the nucleotides in the mRNA are part of codons for the new protein. However, in eukaryotes only, there are extra sequences in the DNA and mRNA called introns, which don't code for proteins.

This mRNA is then further processed:

No one knows why this processing occurs in eukaryotes. Finally, at any one moment, many genes are being transcribed simultaneously according to the cell's needs for specific proteins.

The working copy of the blueprint (mRNA) must now go the construction site where the workers will build the new protein. If the cell is a prokaryote such as an E. coli bacterium, then the site is the cytoplasm. If the cell is a eukaryote, such as a human cell, then the mRNA leaves the nucleus through large holes in the nuclear membrane (nuclear pores) and goes to the endoplasmic reticulum (ER).

Next, we'll learn about translation — the assembly process.

To continue with our house metaphor, once the working copy of the blueprint has reached the site, the workers must assemble the materials according to the instructions; this process is called translation. In the case of a protein, the workers are the ribosomes and special RNA molecules called transfer RNA (tRNA). The construction materials are the amino acids.

First, let's look at the ribosome. The ribosome is made of RNA called ribosomal RNA (rRNA). In prokaryotes, rRNA is made in the cytoplasm; in eukaryotes, rRNA is made in the nucleolus. The ribosome has two parts, which bind on either side of the mRNA. Within the large part are two "rooms" (P- and A-sites) that will fit two adjacent codons of the mRNA, two tRNA molecules and two amino acids. At first, the P-site holds the first codon in the mRNA and A-site holds the next codon.

Next, let's look at the tRNA molecules. Each tRNA has a binding site for an amino acid. Because each tRNA is specific for a single amino acid, it must be able to recognize the codon on the mRNA that codes for that particular amino acid. Therefore, each tRNA has a specific three-nucleotide sequence called an anti-codon that matches up with the appropriate mRNA codon, like a lock and key.

For example, if a codon on mRNA has the sequence ... uracil-uracil-uracil ... (UUU), which codes for the amino acid phenylalanine, then the anti-codon on the phenylalanine tRNA will be adenine-adenine-adenine (AAA); remember that A binds with U in RNA. The tRNA molecules float in the cytoplasm and bind free amino acids. Once bound to amino acids, the tRNAs (also called amino-acyl tRNAs) will seek out ribosomes.

Finally, let's look at the events in the synthesis of new proteins. For example, let's consider a small mRNA molecule with the following sequence:

We know this sequence of amino acids by using a table of the genetic code. The genetic code table above is for mRNA and specifies the bases in the first, second and third positions of the codon with their corresponding amino acids.

Let's read the amino acid specified by the mRNA codon, AUG, using the table at the top of the page. First, place your left finger on the first position codon (A), in the first column of the table. Move your left finger across the row under the second position codon (U) in the first row. Now, place your right finger over the third position codon (G) in the same row of the last column (G). Move your right finger across the row until it meets your left finger and read the amino acid. You should see methionine.

Now let's look at the order of events in the synthesis of our protein from our sample mRNA:

Several ribosomes can attach to a molecule of mRNA one after another and begin making proteins. So, several proteins can be made from one mRNA. In fact, in E. coli bacteria, translation of the mRNA begins even before transcription is finished.

In the human genome, there are 50,000 to 100,000 genes. As DNA polymerase copies the DNA sequence, some mistakes occur. For example, one DNA base in a gene might get substituted for another. This is called a mutation (specifically a point mutation) or variation in the gene. Because the genetic code has built-in redundancies, this mistake might not have much effect on the protein made by the gene.

In some cases, the error might be in the third base of a codon and still specify the same amino acid in the protein. In other cases, it may be elsewhere in the codon and specify a different amino acid. If the changed amino acid is not in a crucial part of the protein, then there may be no adverse effect. However, if the changed amino acid is in a crucial part of the protein, then the protein may be defective and not work as well or at all; this type of change can lead to disease.

Other types of mutations in DNA can occur when small segments of DNA break off the chromosome. These segments can get placed back at another spot in the chromosome and interrupt the normal flow of information. These types of mutations (deletions, insertions, inversions) usually have severe consequences.

There is lots of extra DNA in the human genome that does not code for proteins. Scientists used to believe noncoding DNA served no real purpose. However, they have recently discovered that at least some of it is integral to the function of cells, such as determining when and where some genes are turned on or off or assisting in protein assembly. These aren't necessarily benign duties. For example, a small change in noncoding DNA that alters the pattern of a critical protein can disrupt normal development and lead to health problems.

The Human Genome Project (HGP) was initiated in the 1990s with the goal of determining the sequence of the entire human genome and to answer some basic questions: What genes were present? Where were they located? What were the sequences of the genes and the intervening DNA (noncoding DNA)? The HGP was an overwhelming success, delivering the first rough draft human genome sequence in 2000 and the final high-quality version in 2003. In the years since, it has paved the way for medical advances in everything from identifying more targeted cancer treatments to diagnosing rare genetic disease.

This task was monumental, along the order of the Apollo space program to put the first man on the moon. The HGP scientists and contractors developed new technologies to sequence DNA that were automated and less expensive.

Basically, to sequence DNA, you place all the enzymes and nucleotides (A, G, C and T) necessary to copy DNA into a test tube. A small percentage of the nucleotides have a fluorescent dye attached to them (a different color for each type). You then place the DNA that you want to sequence into the test tube and let it incubate.

During the incubation process, the sample DNA gets copied over and over again. For any given copy, the copying process stops when a fluorescent nucleotide gets placed into it. So, at the end of the incubation process, you have many fragments of the original DNA of varying sizes and ending in one of the fluorescent nucleotides.

DNA technology will continue to develop as we try to understand how the elements of the human genome work and interact with the environment.