7. How DNA Works (933;8/17;pre-RL)

How does a string of letters—really, a string of molecules—actually do anything? In this chapter, we shift our focus from structure to function and examine how DNA works.

If we were to take a stroll down a strand of DNA, we could announce the letters of the DNA nucleotides as we passed them: ATGTCGGATAGATGA, for example. A genetic code that provides the instructions for making a protein is hidden in these 15 letters. Every protein in your body starts as a DNA sequence like this, but much longer.

Reading the genetic code is surprisingly simple. The code works by assigning every possible three-letter combination of DNA nucleotides to one of the 20 amino acids. These three-nucleotide combinations are called codons. For example, we would interpret our earlier sequence ATGTCGGATAGATGA by grouping it into three-letter codons. Grouped in threes, the sequence becomes: ATG TCG GAT AGA TGA. 

This series of codons represents the instructions to make a very small five amino acid protein. Each one corresponds to a specific amino acid. The first codon in our small gene, ATG, for example, specifies the amino acid methionine (abbreviated "Met"). The first amino acid in our protein will be methionine. The second amino acid is specified by the second codon, TCG, which corresponds to the amino acid serine (Ser).

Think of a three-letter codon as a word in a spoken language. Think of an entire gene as a sentence. In other words, a gene (sentence) is a string of codons (words) that has meaning to the cell. 

The entire genetic code can be succinctly presented in a codon chart (see figure) that specifies codon-amino acid correspondence. To read the chart, start on left-hand side and select a letter: T, C, A or G. That will be the first letter of the codon. Next select a second letter from the top list and then a third letter from the right hand options.

For example, let's say we select C from the left-had ("First base in the codon") list. Then we select A from the top, horizontal list and then G from the right-hand lists. That gives us the codon CAG, which corresponds to the amino acid glycine (Gly).

Given that there are three bases per codon, a stretch of DNA 450 bases long will yield 150 codons. With a 150-codon gene, the cell can make a protein that’s 150 amino acids long. Just as DNA’s structure makes copying possible, its nucleotide sequence, read as triplets, makes it readable. 

There one twist to this story. Because the DNA genome resides inside the nucleus but protein synthesis occurs in the cytoplasm, the cell needs a way to transport genetic information: a molecular intermediary capable of crossing the nuclear membrane.

This job is performed by a type of RNA called mRNA. The “m” stand for “messenger,” which is fitting since, again, mRNAs ferry genetic instructions from the DNA to ribosomes, the protein-manufacturing machines in the cytoplasm I mentioned in Chapter 3.

Think of a mRNA molecule as akin to a photocopy of the code contained in a gene--one written in single-stranded RNA rather than double-stranded DNA. This mRNA photocopy will be used in the cytoplasm to synthesize the protein in a process called transcription.

So, to summarize, to make a protein, the cell must know the order of its amino acids. That information is encoded as genes in DNA. But that information in the gene is turned into an mRNA photocopy that leaves the nucleus and is physically used to construct the protein.

This is a good place for me to introduce a law-like generalization in the field of molecular biology known as Central Dogma. It concerns the flow of genetic information between three kinds of biomolecules: DNA, RNA and proteins. This principle was proposed by Francis Crick of Watson and Crick fame in 1958 but still (more or less) holds up today.

Crick first presented Central Dogma as a diagram (see Figure __). The diagram shows the three type of biomolecules--DNA, RNA and proteins--listed from left to right with rightward pointing arrows between them, and with one circular arrow associated only with DNA. It encapsulates several truisms.

First, the two arrows between DNA, RNA and proteins indicate that genetic information in cells flows in only one direction: from DNA to RNA to proteins. The flow of genetic information from DNA to RNA occurs in the process previously mentioned: transcription. The mechanism for transferring information between an mRNA and a protein is called translation.

The second truism--implied by the lack of left-pointing arrows--is that information cannot flow in the other direction: from proteins to RNA to DNA. But since then, in 1970, scientists did discover enzymes that use RNA to synthesize and exact copy in DNA. But these exceptions don't invalidate the rule that genetic information generally flows from DNA to RNA, and then to protein.

The diagram’s third truism is represented by the circular arrow. It indicates that information encoded in a DNA molecule can be copied to create another identical DNA molecule. This process is called replication. It occurs every time a cell divides and requires two genomes for each of the two new daughter cells.

Let's concluse this chapter by using the Central Dogma diagram to orient ourselves. The next chapter is focused on the first arrow in the diagram: transcription. The chapter after that will cover the second arrow: translation. Genome replication, the circular arrow, will be the subject of the entire second half of this book.

For now, though, let's set our sights on transcription and the synthesis of mRNAs--our genetic information messengers--in the nucleus.