A Closer Look at DNA
Read on to learn about DNA structure and function as well as the role of DNA damage and alterations in disease.
DNA is an acronym for deoxyribonucleic acid. Its structure is complex, comprising two long helical strands of smaller molecules called nucleotides.
The three chemical components of a nucleotide are:
- sugar group
- phosphate group
- nitrogen base
Alternating sugar and phosphate groups form the structural backbone of DNA, according to the National Human Genome Research Institute (NHGRI). Each sugar group is attached to a nitrogen base.
There are only four different bases in DNA:
- adenosine (A)
- thymine (T)
- guanine (G)
- cytosine (C)
The specific order of the nucleotides is the sequence of the DNA molecule.
Human beings all have the same general DNA sequence that makes us a distinct species. This is the human genome. Variations in our genomes make us look, feel, and function differently from our parents and friends.
Some of this sequence is organized into genes. A gene is a code for building a protein, though some genes — called noncoding genes — do not perform this action.
The human genome contains about 30,000 genes that code for a protein. They vary in size, from 1,000 to 1 million bases long. Making a protein from a gene is a complex process, which this article describes in a later section.
A 2018 study that has not yet undergone peer review suggests that there are about 1,000 more protein-coding genes than scientists originally estimated.
Surprisingly, only 1% of the genome corresponds to genes. The rest of it plays a role in regulating “when, how, and how much of the gene and protein to make,” explains the NHGRI.
DNA is the instruction booklet for your body to:
- grow from a fertilized egg
- reproduce (have children)
To carry out all of its functions, the cell has to read the booklet to make proteins from the 30,000 genes it contains. The sections below explain how this happens.
Getting from DNA to protein
Simply put, getting from DNA to a protein is a two-step process. The cell must first make an exact copy of the gene into a form that can make a protein. This copy is messenger RNA (mRNA). The process of making mRNA is known as transcription.
mRNA is a single stranded nucleic acid. It has a ribose sugar group versus DNA’s deoxyribose. It also has the nitrogen base uracil instead of thymine (T).
Second, the cell reads the mRNA, three bases at a time, to lay down the building blocks of the protein. These building blocks are called amino acids. The process of making a protein is known as translation.
Each three-base sequence is a codon. There are 61 possible codons that code for 20 possible amino acids. Three codons act as “stop signs” for translation. The stop codon marks the end of the protein.
For example, G-C-A codes for the amino acid alanine, and U-C-A codes for the amino acid serine. The cell translates the mRNA with the corresponding amino acids until it reaches a stop codon.
The cell assembles the amino acids into a protein that performs a specific function in the cell.
The codon-to-amino acid recipe is the “genetic code.” It is universal, with nearly all life forms using it.
To understand the role of DNA in disease, it helps to know a little about genetic variation and DNA mutations.
All human beings have the same basic set of genes and proteins necessary to develop from a fertilized egg. However, there are thousands of differences in your genome that make you different from your family members and peers.
Single nucleotide polymorphisms
Some of these differences are single nucleotide polymorphisms (SNPs). For example, in a stretch of DNA, you might have a cytosine (C) while your friend has a thymine (T).
SNPs occur about every 1,000 nucleotides, so you have a lot of them, explains the National Library of Medicine (NLM).
Any given SNP is also very common, occurring in about 1% of the population. Researchers have identified more than 600 million SNPs around the world. Some SNPs are more common in some populations than others. SNPs can even run in families.
Technically, an SNP is a mutation in the DNA sequence. Historically, however, scientists have tended to consider a mutation a rare event. When a particular difference is very common, it is an SNP.
Most SNPs are harmless because they occur throughout your DNA and not in a protein-coding gene. Even if one does occur in a protein-coding gene, the SNP may not change the amino acid. That is because there is redundancy in the genetic code.
One or more SNPs do not usually cause a specific disease, but they may increase the chance of developing it. For example, you may have an SNP related to an increased risk of diabetes. They can have other effects as well, such as influencing how you respond to a certain drug.
According to the NLM, SNPs that lead to a change in an amino acid are known as substitution variants. They are not common in the general population, but they may be common in certain groups of people or even within a family. Substitution variants can change how the protein functions and may lead to disease.
For example, the mutation responsible for sickle cell disease is one nucleotide difference in the gene that codes for hemoglobin. The resulting codon translates to the amino acid valine instead of glutamic acid, which creates an atypical form of hemoglobin.
There are many more types of variations — including insertions, deletions, and duplications of large chunks of DNA — all of which can have more serious effects on a person’s health.
Many health conditions are due to a combination of SNPs and other variations in many genes or interactions between these gene variations and the environment. These are known as polygenic conditions. Examples include schizophrenia, type 2 diabetes, and cancer.
You can inherit some variations, or mutations, because you get half your DNA from your biological mother and half from your biological father.
Inherited mutations that lead to disease are known as genetic diseases, conditions, or syndromes. Sickle cell disease is one such example.
However, genetic anomalies can also occur later in life and lead to disease. Sometimes, mutations are the result of mistakes during cell division. Other times, they occur due to direct damage to the DNA. They can also result from a combination of these things.
Mistakes in DNA replication
When a cell needs to make a copy of itself, it grows and then divides into two. It produces a copy of its DNA — one for itself and one for the new cell. This is known as DNA replication. When the cell divides, each cell gets its own double stranded DNA molecule.
Sometimes, however, the replication machinery makes a mistake, such as copying the wrong nucleotide. Organisms have evolved to correct these types of errors in a variety of ways. That said, they do not always catch the error, and the variation remains in all other cells afterward. These variations may or may not be harmful, depending on the specific variation and where it occurs.
DNA damage can also drive genetic variation and certain effects on your health. The number of DNA-damaging events that occur per day can be in the tens of thousands, according to some estimates.
DNA damage can be due to:
- UV light
- free radicals
- toxins and chemicals
Your body has many ways of repairing the damage, but sometimes it remains. When a cell copies DNA and divides before repair, it can cause mutations. As with DNA replication errors, these mutations may have no effect at all or lead to distinct changes in a cell.
Two primary effects of DNA damage are cancer and aging.
By chance, if a mutation occurs in a gene involved in DNA repair, it may block the ability of the cell to repair its DNA. This can lead to more mutations than usual. As the cell continues to divide, it generates more, potentially dangerous mutations.
Mutations can also occur in genes that manage cell division. Some mutations may change how and when the cell divides. The cell may continue to grow and divide when it is not supposed to. This can lead to uncontrollable cell growth and cancer.
You can also be born with one or more mutations that increase your risk of developing cancer.
Cell death and aging
If the cell cannot repair the damage, the damage persists and tells the cell to stop dividing. This pathway protects you from cancer because a cell that divides with damaged DNA increases the risk of developing cancer.
However, a cell that no longer divides has a sort of “self-destruct” button, and the cell dies. This action is known as programmed cell death, or apoptosis.
As with cancer development, DNA damage that leads to aging accumulates slowly over your lifetime.
Damage to RNA and proteins also contributes to aging. An example is certain proteins in nerve cells. They can form large clumps as the cells age, which reduces the ability to function.
Researchers clarified the structure of DNA in 1953. This was the work of Rosalind Franklin, Maurice Wilkins, James Watson, and Francis Crick.
By studying pure crystals of DNA and building models, they determined that the 3D structure is two strands of DNA wound around one another. This is a double stranded DNA molecule. Watson and Crick named it the double helix.
Think of a twisted ladder with rails and steps. The rails of the ladder are the sugar-phosphate groups, and each step is a pair of nitrogen bases, one from each rail.
The nitrogen base pairs are very specific because of the chemical bonds they form. This feature generates the helical structure of double stranded DNA. The nitrogen-containing bases adenine (A) and thymine (T) form one type of pair, and guanine (G) and cytosine (C) form the other.
DNA is deoxyribonucleic acid. Your cells read the DNA to make proteins necessary for your body to develop and survive. It gives you the ability to reproduce and pass genetic information to your offspring.
DNA also plays a role in disease and aging. Throughout your life, environmental factors and life itself cause DNA damage. Your cells have sophisticated methods of repairing this damage, but the damage can lead to cancer-driving mutations and aging over time.
You can help minimize the amount of DNA damage that occurs by living a healthy lifestyle, such as by avoiding excessive exposure to UV light.