7. How DNA Works (1060;9/11;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.

The Genetic Code

If we were to take a stroll down one of the strands of a DNA double helix, we could announce the letters of the DNA nucleotides as we passed them: for example, ATGTCGGATAGATGA. A genetic code providing the instructions for synthesizing 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 to know the right amino acids to connect linearly to make a protein 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 sequences are called codons. We would interpret our earlier sequence--ATGTCGGATAGATGA--by grouping it into three-letter codons: ATG TCG GAT AGA TGA. 

This series of codons represents the instructions to make a very small five amino acid protein. The first codon in our gene, ATG, specifies the amino acid methionine (abbreviated "Met"). Thus, 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). And so on.

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 presented in a codon chart (figure) that specifies correspondences between codons and amino acids. 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. 

RNA and mRNA

There's one more layer 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 the gene sequence from the nucleus to the cytoplasm. It needs a molecular intermediary capable of crossing the nuclear membrane. The cell will use RNA molecules for this purpose.

Like DNA, RNA molecules are chains of nucleotides (i.e., polymers). But RNA nucleotides aren't identical to DNA nucleotides. The backbone components of the nucleotides differ by one small chemical attachment.

In addition to being composed of slightly different molecules, RNAs are also generally single-stranded whereas DNA molecules are generally double-stranded (i.e., they take the form of a double helix). The double stranded-ness of DNA enables it to replicate itself. RNA molecules don't self-replicate.

Finally, one of the four nucleotides differs between RNA and DNA. RNA nucleotides include uracil (U) rather than thymine (T). So the four RNA nucleotides are named using the letters A, G, C, and U rather than A, G, C, and T. Like the "T" DNA nucleotide, the "U" RNA nucleotide pairs with "A."

The job of transporting genetic information from the nucleus to the cytoplasm is performed by a specific type of RNA called an mRNA. The “m” stand for “messenger.” Think of mRNAs as photocopies of the DNA master copy of a gene. These photocopies are effectively "mailed out" into the cytoplasm where they're used by protein manufacturing machines called ribosomes to make proteins.

The creation of an mRNA using the gene as the template is called transcription. We'll be discussing mRNAs and transcription in more detail in the next chapter.

Central Dogma

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

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

First, the two rightward pointing arrows--one between DNA and RNA, and the other between RNA and protein--indicate that genetic information in cells flows in one direction only: from DNA to RNA to proteins. The flow of genetic information from DNA to mRNA 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. Today we know that there are a few exceptions to this rule. In 1970, scientists discovered enzymes that do use RNA to synthesize DNA. But the exceptions don't invalidate the rule that genetic information generally flows from DNA to mRNA to protein.

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

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