How Does DNA Work?
How does DNA work? Today we're taking a conceptual overview of the amazing facility of DNA: what it looks like, how it relates to chromosomes and genes, and how it translates to life-sustaining protein products.
DNA stands for deoxyribonucleic acid. It's made up of four base pairs (A, T, C, G) that code for all the proteins in your body.
The DNA double helix is a beautiful molecule, evolved over billions of years, to create the diversity of all life on Earth.
Today we'll look at how DNA is coiled, replicated, and expressed on a moment-to-moment basis in order to create and sustain your life.
What is DNA?
DNA is a self-replicating molecule that resides in the nucleus of every cell of your body. Think of it as a recipe book for making a human being from scratch.
Inside the recipe book are chapters which represent chromosomes. There are 46 chromosomes in your cells: 23 come from your mother, and 23 come from your father. When you lay them out in their corresponding pairs, you get your karyotype.
Different species have different numbers of chromosomes. For instance, rats have 42 chromosomes making up their DNA. Chickens have 78 chromosomes. And butterflies have really run away with the idea, evolving 380 chromosomes.
The number of chromosomes isn't down to an organism's complexity—but rather the pathway in its evolution. Evolution is driven by deletions, duplications, and mutations in DNA. The whole process is random; no-one's doing any housekeeping. So after hundreds of millions of years, there's a lot of redundancy passed on in DNA.
Back to the recipe book. If chromosomes are chapters, then genes are individual recipes in each chapter.
Some traits are determined by a single gene: examples include long eyelashes, a chin fissure, or brown eyes. However, most traits are the result of multiple gene interactions, such as intelligence, autism, or coat colour if you're a Golden Retriever.
We'll look at how genes are expressed in a moment. First, let's take a look at how genes, chromosomes, and DNA relate to each other.
How Genes Form Chromosomes
Take a moment to visualise the the process of thousands of base pairs making up genes, which coil into chromosomes to form your complete set of DNA.
- Base pairs, in their thousands or millions, form genes.
- Genes reside in the double helix.
- The double helix winds into nucleosomes.
- Nucleosomes coil and twist into supercoils.
- Supercoils fold into loops to form chromosomes.
- Chromosomes collectively make up DNA.
This bundling and coiling is a finely tuned process. Different coiling styles occur in different cells appropriate to local gene expression.
In other words, although every cell in your body contains eye colour genes, the DNA in your iris cells coil to make the pigment genes more accessible for expression.
The coiling process happens a lot. Every time a cell divides (every few hours or days, depending on the cell's role) all 46 chromosomes uncoil into vast stretches of DNA. This exposes the base pairs for replication, before it re-coils into its resting state in chromosome form.
The Molecular Structure of DNA
From now on, we're going to zoom in and look at how DNA works very closely indeed.
The double helix shape of DNA was made famous by Watson and Crick in 1953. However, few people know that this discovery was dependent on many other scientists before them, including Rosalind Franklin's X-ray crystallography which provided the critical clue to its structure.
We can think of DNA as a molecular jigsaw puzzle. Except there are only six different shapes and 18 billion pieces overall.
The six shapes in question the DNA bases (adenine, thymine, guanine, and cytosine) and the DNA backbone (sugar rings and phosphate groups).
Due to their chemical structures, the bases and backbone are compelled to join together like a ladder. This is how we find a beautiful order emerging out of apparent chaos, allowing for the evolution of life.
How DNA Bases Create Genes
How do these chemical molecules relate to genes? Frank Ryan has an analogy in his wonderful book, The Mysterious World of The Human Genome:
Imagine yourself in a landscape with a train track stretching out to the horizon. The rails represent the sugar-phosphate backbone of DNA, while the sleepers represent the complementary base pairs (A with T; G with C).
The train track is very long. As you walk along it, you can count off hundreds, then thousands, then millions, then billions of sleepers.
There are 27,000 of these sleepers in the average gene, although some are as long as two million. That's quite a lot of train track. If you were to examine your entire genome—that's all your DNA combined—you would have to walk along three billion sleepers (or six billion bases in total).
The precise sequence of base pairs are the blueprints to make specific proteins. Proteins aren't just the nourishment you get from milk; they form the basis of all living tissues. They're also key to biological processes: catalysing reactions, transporting molecules around the body, and transmitting messages between cells. Your body is built on proteins.
(Surprisingly, not every base pair is considered to form coding DNA. Far from it. In humans, it appears only 2% of our DNA codes directly for making proteins. The other 98%—referred to as non-coding DNA or junk DNA—is a mixed bag of knowns and unknowns.
Some stretches have been identified as regulatory DNA which instructs the DNA how to replicate. Other stretches have been identified as viral DNA inserted into your genome when you get sick. The rest is largely a mystery.)
Now we have the structural intricacies covered, how does DNA work?
Recall that DNA is like a recipe book: chromosomes are the chapters and genes are the recipes. In this analogy, who's the cook? Who's mixing the ingredients? And what do they make?
This is the process of gene expression, and it's happening all the time in your body to produce those life-sustaining proteins on demand.
There's lot's going on during rapid growth phases, like embryonic development and puberty. But genes are also essential for day-to-day living, such as making insulin if you've just had breakfast, or cortisol to regulate your stress response.
Gene expression takes place in three stages, known as the Central Dogma because it's so very important to how DNA works:
- Transcription (copying the recipe)
- RNA Processing (customising the recipe)
- Translation (converting the recipe into a dish)
Let's look at this molecular dance in more detail.
Step 1. Transcription Photocopies The Recipe
In DNA transcription, the helical DNA unwinds to expose the gene(s) to be expressed and makes a copy in the form of a molecule called RNA.
(RNA stands for ribonucleic acid. It's thought to be the evolutionary precursor to DNA, and has three key differences. RNA is single-stranded (DNA is double-stranded), and contains the base uracil (DNA contains thymine) and the sugar ribose (DNA contains deoxyribose.)
Copying DNA into RNA is like taking a photocopy of the recipe to work with. Imagine your kitchen is messy and you often set things on fire; you want to keep your very important recipe book nice and clean for future use.
(Remember, you like to cook thousands of times a day, and there's no way to buy a new recipe book if you damage this one.)
During DNA transcription:
- RNA polymerase travels along the DNA helix, teasing apart the two strands.
- Free-floating bases are attracted to their complementary partners along one strand of the DNA.
- The new strand of RNA now serves as the recipe photocopy, ready for meal prep.
Step 2. RNA Processing Customises The Recipe
In RNA processing the new strand of RNA (the photocopied recipe) goes through some important modifications:
- The RNA receives a cap and tail, determining how long it should be expressed.
- Spliceosomes remove non-coding bases (introns) and leave behind only coding bases (exons).
- Alternative splicing of RNA allows for different gene combinations to produce different proteins.
There is a pretty spectacular bit of biology going on here. The end product of gene expression all depends on which exons are spliced during RNA processing.
It means the same stretch of genetic code can be expressed in numerous ways, which is super efficient. It's ironic, then, that so much of DNA is non-coding junk, which is super inefficient. Damn you, nature.
Step 3. Translation Executes The Recipe
The third stage of gene expression is called translation because there is a change of language: from bases to amino acids.
The spliced RNA strand exits the cell nucleus and enters the cell cytoplasm. Here, it attaches to a ribosome, a molecular complex that holds the base sequence in groups of three (called codons).
Transfer RNA, or tRNA, is the critical translator here, while the ribosome holds everything in place. Each tRNA has a complementary anti-codon on one end, and an amino acid counterpart on the other. Molecular attractions take care of the rest.
What emerges is a long string of amino acids, also known as a polypeptide chain. These are the foundations of proteins, with multiple polypeptides folding into specific functional shapes.
The Genetic Code
"Tell me more about the codons!" I hear you scream. And you'd be right. This is a good thing to scream about, if anything is.
The relationship between codons and amino acids is defined in the genetic code, universal to all life on Earth.
For instance, the base sequence, or codon, C-G-C translates to the amino acid arginine. And the codon A-T-G translates to methionine, as well as being the signal to start building a polypeptide.
Here's the complete genetic code:
The genetic code has provided us with some fascinating insights into disease and evolution. For instance, we now know there are 64 possible codons in all (4 x 4 x 4) and only 20 amino acids. So multiple codons translate to the same amino acid, creating redundancy in the genetic code.
However, this is a good thing because it dampens the effects of mutations. A switch from G-T-T to G-T-C still codes for valine, thereby preventing a valine deficiency which causes neurological defects.
See my article on Animal Evolution to learn how genetic mutations can be good, bad, or neutral in our survival. Also What Happened to Gene Therapy? for an overview of how gene therapy repairs DNA errors.
How Fast is Gene Expression?
All of this takes place at an astonishing rate. A single ribosome can produce dozens of polypeptide chains every second.
And there are up to 10 million ribosomes in a typical body cell, enabling for simultaneous translation on a massive scale.
This, a single cell can throw out vast numbers of protein molecules on demand, and does so alongside thousands of other cells.
And that's pretty much how DNA works. At least, it's the simple version. Those who study these molecules in the lab have a profound understanding of the physical, chemical, and biological interactions at play—and continue to advance that knowledge all the time.
The take-home point is this: DNA and its entourage perform a continual and complex choreography, culminating in the normal functioning of any living organism, such as a friendly newt or toad. Isn't that brilliant?