Introduction To Mutation
Mutation is well-popular in genetic and evolutionary studies. Mutations cause variations and it violates the Hardy-Weinberg equilibrium stating that evolution occurs due to mutation.
Mutations are the changes that occur in the genetic makeover of the DNA sequences. This means that mutation causes changes in the nitrogenous base sequence of the DNA like removing one nitrogenous base and adding another to each nucleotide of DNA.
A mutation is a permanent alteration of a gene’s DNA that makes the altered gene differ from what it is found in most organisms.
Mutation is also a mechanism of evolution that causes variations due to changes in the genes’ DNA sequence in an organism.
Gene mutations can occur in two major ways: Hereditary mutations that occur during a person’s life are inherited from a parent, and Acquired mutations that occur during a person’s life are neither inherited nor can be passed to the next generation.
Gene mutations can be of two types: Point Mutation that arises due to change in a single base pair of DNA, and Frameshift Mutation that arises due to loss (deletions) or gains (insertions) on one or two bases in the DNA.
Below there are some of the most prominent examples of mutations that will help you understand the concept of mutation better and precisely…
Examples of Mutations in Zoology
Example 1. Sickle cell anemia
Sickle cell anemia disease is caused by a mutation in the β-globin gene found on chromosome 11.
This β-globin gene on Chromosome 11 normally signals the body to make hemoglobin in RBCs that will carry oxygen from your lungs throughout the biological body.
There are two subunits that makes up the normal hemoglobin protein: 2 β-globin chains and 2 α-globin chains. The RBCs with normal hemoglobin are smooth and round and glide through blood vessels easily.
When point mutation occurs in the β-globin gene it causes sickle cell anemia, i.e. it will now signal the body to make altered hemoglobin that will make the RBCs become rigid, sticky, and misshapen.
Sickle-cell anemia is caused by a point mutation in the β-globin chain of hemoglobin, causing the hydrophilic amino acid glutamic acid to be replaced with the hydrophobic amino acid valine at the 6th position.
This type of mutation is inheritable, and both mom and dad must pass the defective form of the gene for a child to be affected.
Example 2. Thalassemia
Thalassemia is another inherited blood disorder that causes our body to have less hemoglobin than normal.
We know that the normal hemoglobin protein has: 2 β-globin chains and 2 α-globin chains. The mutant gene makes the sufferer unable to synthesize one of the globin chains resulting in the excess of the other.
In this condition, the free globin chains which are insoluble don’t form normal hemoglobin, and accumutate inside the RBCs and form precipitates that damage the RBCS.
Based on which globin chain is defective, Thalassemia is classified into two categories: α-Thalassemia and β-Thalassemia.
α-Thalassemia is caused due to point mutation on one or both alleles of two α-globin genes (HBA-1 & HBA-2) present on Chromosome 16. The mutated globin gene fails to synthesize α-globin chain, resulting in the excess of β-globin chain in adults, thus showing abnormal oxygen dissociation curve.
β-Thalassemia is caused due to mutation in the HBB gene that codes for β-globin chain of hemoglobin on Chromosome 11. The mutated globin gene can terminate the formation of β-globin chain or can lead to formation of only a few β-globin chains.
The difference between Thalassemia and Sickle cell anemia is that, Thalassemia is caused due to the excessive formation or termination of alpha-globin and beta-globin genes due to mutation.
Whereas, Sickle cell anemia is caused due to the formation of abnormal hemoglobin due to mutation of the β-globin gene.
Example 3. Cystic fibrosis
Cystic fibrosis is a hereditary disease caused due to mutation that affects the lungs and digestive system.
Due to Cystic fibrosis, the body produces thick and sticky mucus that can clog the lungs and obstruct the pancreas for doing its normal metabolic activities.
Cystic fibrosis is caused by a point mutation in the CFTR gene (cystic fibrosis transmembrane conductance regulator gene). This occurs due to the deletion of three nucleotides in the CFTR gene that is found on Chromosome 7.
The CFTR gene, found on chromosome 7 is a 230,000 base pairs long and creates a protein that is 1,480 amino acids long.
The normal CFTR gene produces proteins that function as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes.
The point mutation that occurs in the CFTR gene causes a loss of the amino acid phenylalanine at the 508th position on the protein.
This mutated gene makes proteins that make mucus that interferes in the function of the exocrine glands like lungs, liver, sweat glands, etc
Cystic fibrosis only happens occurs when both inherited CFTR genes (one from mom and the other from dad) in the pair have a mutation.
Example 4. Phenylketonuria (PKU)
Phenylketonuria (PKU) is an inherited disorder caused due to mutation that increases the levels of amino acid phenylalanine in the blood.
Phenylketonuria is caused due to point mutation in the PAH gene that is found on chromosome 12. The human PAH gene shows more than 520 different mutations that have been characterized in PKU patients and recorded.
The normal PAH gene can signal to make an enzyme called phenylalanine hydroxylase that catalyzes the conversion of phenylalanine amino acid into tyrosine to form phenylpyruvate and other derivatives.
When the PAH gene gets mutated, the body cannot break or catalyze down phenylalanine amino acid, thus mental retardation, intellectual disabilities, seizures, behavioral problems, and mental disorders occur as phenylalanine accumulates in the brain.
This type of mutation is inherited when both mom and dad pass the mutated form of the PAH gene for a child to be affected. This means that if both parents have PKU, their child will have PKU as well.
Example 5. Color blindness
Color blindness (also known as color deficiency) occurs when you are unable to see and distinguish different colors in a normal way. The affected individual cannot distinguish between green and red color and often blue color.
Red-green color blindness is the most common type of color blindness in which the person is unable to differentiate between red or green color.
Blue-yellow color blindness defects (also called Tritan defects), which are rarer, cause problems with differentiating shades of blue and green and cause difficulty distinguishing dark blue from black.
These two forms of color blindness i.e. Blue-yellow color blindness and Red-green color blindness disrupts color perception but do not affect the sharpness of vision.
Mutations in the OPN1LW, OPN1MW, and OPN1SW genes cause the above mentioned two types of color blindness.
OPN1LW and OPN1MW genes are located in X-chromosome and OPN1SW gene is located on Chromosome 7.
Mutations particularly in the OPN1LW or OPN1MW gene cause red-green color blindness. Whereas, mutations in the OPN1SW gene cause blue-yellow color blindness.
It is to be noted that the normal OPN1LW, OPN1MW, and OPN1SW genes are present in the cones of the eye’s retina. These genes produce opsin proteins that play essential roles in color vision.
Red-green color blindness is inherited when a female contains each mutated recessive OPN1LW & OPN1MW genes in both X chromosomes. And, in male one genetic change in each cell is sufficient to cause the condition.
Blue-yellow color blindness gets inherited when one copy of the mutated OPN1SW gene gets transferred to the offspring either from mom or dead or both.
Example 6. Cri-du-chat-syndrome
Cri-du-chat syndrome is a chromosomal condition that results when a piece of chromosome 5 is missing. Infants with this condition often have a high-pitched cry that sounds like that of a cat.
This syndrome shows intellectual disability, delayed development, small head size, low birth weight, widely set eyes, weak muscle tone, low-set ears, a small jaw, and a rounded face in the affected infants.
Cri-du-chat syndrome is caused due to deletion mutations of the end of the short (p) arm of chromosome 5, due to which specific gene named CTNND2 along with other genes gets removed from the chromosome.
The more the deletion mutations of the end of the short (p) arm of chromosome 5 occurs the more types of disabilities it creates than smaller deletions.
Cri-du-chat syndrome in 90% of cases is caused due to random mutations during the meiosis cell division of eggs or sperm.
And, only about 10% of people with Cri-du-chat syndrome inherit the chromosome abnormality from an unaffected parent.
Example 7. Opitz-Kaveggia syndrome
Opitz-Kaveggia syndrome (OKS) is an X-linked recessive mental retardation syndrome that affects intelligence and behavior.
It is symptoms like abnormal body structures, overly large head, widely set eyes, down slanted palpebral fissures, prominent forehead with frontal hair upsweep, and broad thumbs and halluces.
Opitz-Kaveggia syndrome (OKS) is also known as FG syndrome (FGS) and it occurs almost exclusively in males.
It is caused due to Chromosomal Inversion Mutation in Chromosome X where one region of a chromosome is flipped and reinserted.
Five prominent regions on the X chromosome have been identified that are well-linked to FG syndrome in affected families.
And, it is also seen that mutations mostly in the MED12 gene appear to be the most common cause of this disorder, leading to FG syndrome.
It is inherited in a Chromosome X-linked recessive pattern meaning that in males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition.
And that, in females (who have two X chromosomes), a mutation usually must occur in both copies of the gene to cause the disorder.
Example 8. Haemophilia
Hemophilia is a rare disorder that is caused by a mutation in which it is seen that the blood clotting process slows down in affected individuals.
In this disorder, the protein involved in the clotting of blood becomes defective due to the presence of a defective mutated gene.
As a result, even a small cut results in non-stop bleeding in the affected individual as the clotting of blood is abnormally delayed.
Mutation in the F8 and F9 genes are responsible for Hemophilia. Mutation in the F8 gene causes Hemophilia A, while mutations in the F9 gene cause hemophilia B.
Both F8 and F9 genes are found close together on the X chromosome.
The normal F8 gene provides instructions for making Coagulation factor VIII whereas, the normal F9 gene provides instructions for making Coagulation factor IX.
Coagulation factors are actually proteins that work together in the blood clotting process.
Mutated F8 and F9 genes code for abnormal versions of Coagulation factor VIII and Coagulation factor IX proteins that causes to slow down the blood clotting process.
Hemophilia A and hemophilia B are inherited in an X-linked recessive pattern. Meaning that, in males, one altered copy of the gene in each cell is sufficient to cause the condition.
And that, in females (who have two X chromosomes), a mutation must occur in both copies of the gene to cause Hemophilia.