How Do Mutations Occur in Human Cells?

Before I begin explaining how mutations occur in human cells, I want you to look around. Do you notice certain differences in the people around you? Your own parents may look slightly or very different from you. Even siblings may have a different eye color or hair color. Some maybe tall and some maybe short.

These differences in the physical make up of each individual is all thanks to their individual DNA. There are many genes in the DNA that lead to polymorphism making each one of us unique. Apart from these changes, you may see some people suffer from defects or disorders related to their genes.

These defects occur due to mutation of genes leading to deviation from the normal variation in people.

Mutations are permanent changes that take place in a sequence of a gene. They tend to alter the behavior of a cell and this causes abnormal functioning of the cell. Mutation in human cells occur due to two reasons. Let us look them below.

These that are inherited from parents are called 'germline' or 'hereditary' mutations. This is because they are present in the egg or sperm cells, called germ cells. These remain in each and every cell of the body for life. The ones that occur only in an egg or sperm cell or just after fertilization are called de novo (new) mutations.

These occur as genetic disorders in a child with no family history of such disorders or defects. So, in simple terms, mutations present on both or either of the parent DNA passed on to the child are called inherited mutations.

They are those that occur in the DNA of individual cells during their life span. These are also called 'somatic mutations' as they occur due to the influence of the environmental factors. These occur at the molecular level due to the presence of certain chemicals in the environment, radiation, ionizing radiation, radioactive decay, viral infections and ultraviolet radiation. They cannot be passed on to the affected person's children.

Mutations can occur due to the mistakes made by the cell when copying or reading the DNA when it prepares itself for cell division. It may even occur due to presence of environmental agents like ultraviolet light, nuclear radiation and chemicals. Let us have a look at the various causes in detail.

Before a cell divides, it has to duplicate its entire DNA sequence. This is called DNA replication that begins after the protein DNA helicase separates the double stranded DNA molecule into 2 separate strands. There are many different types that can occur when protein DNA polymerase copies these single stranded DNA to make 2 double stranded DNA molecules.

They occur only when DNA polymerase makes a mistake once every 100,000,000 bases. The bases include adenine (A), thymine (T), guanine (G) and cytosine (C). Adenine always pairs with thymine and guanine forms pairs with cytosine. Any alteration in these sequences will result in mutations.

It is a single change in the one base of the gene sequence. For example, let us suppose that DNA polymerase was to read the following sentence for replication:

Correct Sequence: Jack and Jill Went Up The Hill
Point Mutation: Jack and Jill Went Yp The Hill

The simple change from 'U' to 'Y' results in point mutation in the progeny.

They are those where one or more bases are either inserted or deleted. When DNA polymerase reads the DNA, it reads it in three 'words'. This means, any changes, shifts, additions or deletions renders that sequence meaningless. Thus, the protein formed from that sequence is shortened or abnormal. For example:

Correct Sequence: Jack and Jill Went Up The Hill
Frame-shift Mutation: Jack and Jill Went Yo hTe Iill

When just one base or chains of bases are deleted from the DNA sequence, it results in deletion mutation. These deletions can also result in frame-shift mutations. A number of genes are affected, thus, the DNA is rendered meaningless. For example:

Correct Sequence: Jack and Jill Went Up The Hill
Deletion Mutation: Jack and Went Up The Hill

Just as bases can be deleted, extra bases can be inserted in a sequence. The result is the same - mutations in the cells that lead to non-functional proteins. For example:

Correct Sequence: Jack and Jill Went Up The Hill
Insertion Mutation: Jack and Jill Went Up Down The Hill

This is a type of mutation that leads to reversal of the entire sequence of the DNA. For example:

Correct Sequence: Jack and Jill Went Up The Hill
Inversion Mutation: Jack and Jill tneW pU ehT lliH

Environmental factors such as chemicals like hydroxylamine (NH₂OH), alkylating agents, DNA adducts, DNA intercalating agents, DNA crosslinkers or radiations like UV radiation, ionizing radiation, radioactive decay or presence of a viral infection can lead to mutations in DNA. These are caused by environmental agents and occur as follows:

When the nucleotide bases are altered, the DNA gets damaged. This can take place in the presence of UV light, nuclear radiation or certain chemicals that have the ability to modify the bases. For example, an altered base T will form a pair with C instead of A, thus, resulting in a mutation.

DNA strands are connected to each other by a phosphate backbone that helps in creation of double stranded DNA. Environmental agents tend to break the bonds between phosphate (P) and oxygen (O) groups, resulting in mutations. These tend to occur in the presence of powerful agents such as nuclear radiation.

When the phosphate backbone is broken, it leads to formation of mutated genes. The DNA will try to fix the broken ends by joining the other pieces of DNA. This may lead to another type of mutation called the translocation.

These mutations lead to mild, moderate to severe symptoms in the affected child or person. They lead to diseases such as sickle cell anemia, Down's syndrome, etc. DNA is the most important aspect for creation of life. Any changes or alterations in DNA will lead to irreversible defects or disorders for life.