Lesson Explainer: Genetic and Chromosomal Mutations Biology • Third Year of Secondary School

In this explainer, we will learn how to define what a mutation is, recognize various types of mutations, and state some potential impacts of mutations.

Mutations are changes in an organism’s genome. For example, a rare mutation in the TYR gene can cause albinism in humans, where the body does not make any pigment in their skin, hair, and eyes. This can result in a person having very pale skin and very white hair. Mutations are incredibly important as they create genetic diversity. They drive evolution and allow species to adapt to changing environments and conditions. Two mutation types exist: genetic and chromosomal mutations.

Let’s take a look at genetic mutations first.

DNA is a long molecule with two sugar–phosphate strands that wind around each other to form a twisting ladder shape called a helix. Inside the helix, attached to the sugar–phosphate backbone, are four DNA bases, adenine (A), guanine (G), cytosine (C), and thymine (T). Its structure is shown in Figure 1. Within DNA molecules, the order and number of the bases can create genes which contain the genetic information to create characteristics and traits.

DNA sequences that encode information for creating characteristics are called “genes.” A gene is a sequence of DNA that codes for a particular protein, which in turn will produce a particular characteristic or version of a characteristic. For example, our genes are responsible for determining our eye color, natural hair color, and blood type and even play a role in how tall we can grow!

So, how does a sequence of DNA become a protein? First, the cell converts DNA sequences into a similar molecular sequence called RNA. The RNA sequence is then “read” by special organelles called ribosomes. Ribosomes translate the RNA into specific protein products that create observable characteristics in the organism. A basic outline of this process is shown in Figure 2.

It should be noted that gene sequences are translated into protein by “reading” the gene sequence in groups of three bases. Every three DNA bases correspond to a specific amino acid. This way of dividing nucleotides into consecutive triplets is called the sequence’s “reading frame.”

When a sequence of mRNA is translated into a protein, a ribosome matches every three mRNA bases to their corresponding amino acid. This allows the cell to create and reproduce a diversity of unique and specific proteins. The reading frame is very important for building the correct protein and expressing its corresponding trait. A codon wheel, such as the one shown below in Figure 3, can be used to determine what amino acid is matched to a sequence of three mRNA nucleotides. For instance, the sequence AGC will give the amino acid serine (ser).

Not all of an organism’s DNA are genes, some DNA has been considered “junk DNA” because it does not encode any information for observable traits! Other DNA sequences provide a location for regulatory proteins or contain repetitive sequences that prevent degradation of the DNA molecule. Even genes have DNA sequences that are removed after transcription into RNA. These removed sequences are called “introns” and are not translated into a protein. Meanwhile, expressed gene sequences are called “exons.”

Genetic mutations are changes in an organism’s DNA base sequence. Genetic mutations arise from DNA copying mistakes or exposure to outside environmental conditions, like UV radiation or harmful chemicals. Mutations can alter an organism’s gene sequences, which encode protein synthesis instructions. If an organism’s gene sequence mutates, its encoded protein sequence may change. As proteins influence an organism’s traits, mutations can ultimately alter an organism’s phenotype (an organism’s physical characteristics).

Mutations can occur anywhere in the genome. Suppose a DNA change occurs outside a gene sequence in junk DNA. In that case, the mutation likely has little or no phenotypic effect, as the mutation does not alter a protein-coding gene. Such a mutation is “neutral,” as the organism has no phenotypic change. However, if the mutation occurs in a gene sequence, the mutation may affect the organism’s phenotype.

Suppose a mutation alters a gene sequence so that its corresponding protein is harmfully altered. In that case, the organism will be harmed by the mutated phenotype. For instance, mutations in the insulin protein’s receptor-binding domain can lead to diabetes, as the insulin receptors no longer function properly.

On the other hand, a mutation can also change a gene sequence to beneficially change its corresponding protein. For example, some people have a mutation in the CCR-5 gene that changes the receptor that HIV uses to get into immune cells, giving them resistance to HIV infections. The organism will then benefit from the mutation. Therefore, mutations may have neutral, harmful, or beneficial effects.

There are several genetic mutation types. Genetic mutation types include substitution, deletion, and insertion mutations.

In a substitution mutation, one DNA base is exchanged for another DNA base at a specific genomic location (a locus). A substitution mutation is depicted in Figure 4. If a substitution mutation occurs in a gene, several different outcomes may occur. If the base substitution does not change the final amino acid sequence encoded (as some amino acids are coded for by more than one codon), the mutation is neutral. Consequently, no observable change occurs.

However, if a substitution within a gene exchanges a DNA base for another so that it encodes a different amino acid in the final protein, such substitution may have either beneficial or harmful phenotypic effects. The base substitution may even encode a stop codon, causing protein translation to stop prematurely, which can produce a nonfunctional protein. This usually has serious detrimental effects on the organism.

In insertion mutations, one or more new base pairs are inserted at a DNA locus. This process is shown in Figure 5.

Conversely, in deletion mutations, one or more existing DNA base pairs are lost at a DNA locus, as shown in Figure 6.

Suppose base pairs are inserted into or deleted from a gene’s reading frame. In that case, this may have severe consequences for the organism. When a number of base pairs other than three or multiples of three are inserted into a gene sequence, the reading frame shifts and results in an entirely different protein sequence. This sequence is likely random and introduces a premature stop codon that results in a dysfunctional protein product that harms the organism. Additionally, this process can introduce a frameshift that changes all amino acids after the change in the DNA code that can harmfully change an organism’s characteristics. This process is shown in Figure 7.

Mutations may be much larger than small genetic mutations and can involve whole chromosomes and chromosome segments. As chromosomes have many genes, chromosomal mutations alter large portions of the chromosomes’ structure, consequently mutating many genes by either deleting or duplicating genes. The collective effect of these mutations usually harms the organism.

Several chromosomal mutation types exist.

In chromosomal duplications, an organism carries one or more extra copies of one or more chromosomes or chromosome segments. A large amount of extra genetic material may be harmful but can give evolutionary advantages. Such advantages have been observed in plants. For example, polyploid plants may have increased leaf and flower size. Many crops are even bred for polyploidy. Organisms with more than two chromosome sets are said to be polyploid.

In chromosomal deletions, one or more whole chromosomes or chromosome segments are lost or deleted. Similar to chromosome duplications, this large change in genetic material amount has significant phenotypic consequences. For example, the Wolf -Hirschhorn syndrome is a chromosomal deletion syndrome resulting from a partial deletion on the short arm of chromosome 4. This deletion causes deformations of the bones of the skull and face and intellectual disability.

In an inversion, a chromosome segment breaks off from the rest of the chromosome and reattaches in the reversed direction. Chromosomal inversions rearrange the chromosome. In humans, chromosomal inversions can cause fertility problems but typically carry no other harmful effects. For example, inversions on chromosome 9 can cause fertility problems.

Chromosomal deletions, duplications, and inversions are shown in Figure 8.

Example 3: Illustrating a Chromosomal Inversion Mutation

The diagram provided shows a simplified outline of the different types of chromosomal mutations that can occur. Which diagram (1, 2, or 3) demonstrates an inversion mutation?

Answer

Several chromosomal mutation types exist. Organisms with chromosomal duplications carry an extra copy (or copies) of a chromosome (or chromosomes) or chromosome segments. In contrast, organisms with chromosomal deletions have chromosomes or one or more chromosome segments that are missing.

The third chromosome mutation type is an inversion: a chromosome segment breaks away from its parent chromosome and reorients itself in the opposite direction. Reoriented, it then reattaches back onto the parent chromosome.

Both mutations 1 and 3 are chromosomal deletions, as chromosome segments are missing compared to the original chromosome.

However, in chromosome 2, the blue and gray segments are reversed between the parent and mutated chromosomes. This chromosome segment most likely broke off from the original chromosome and reattached to the chromosome in the opposite direction.

Therefore, mutation 2 is an inversion mutation.

Mutations arise through different mechanisms. Spontaneous mutations occur randomly and arise from natural biological processes like DNA replication errors in sperm and egg production. Spontaneous mutations typically affect all of an organism’s cells, including their reproductive cells, and will be passed on to its offspring.

On the other hand, induced (or acquired) mutations may arise from certain environmental substances and conditions that mutate DNA. Such conditions and substances are considered “mutagenic,” as they generate many acquired mutations in organisms. These induced mutations exist only in some body cells.

Mutagenic substances and conditions include UV radiation, harmful chemicals, and carcinogens (substances that cause cancer). Acquired mutations can be incredibly destructive. If an acquired mutation occurs in a cell cycle gene, it may cause cancer. Consequently, mutagenic substances are incredibly hazardous.