Viable Errors During Replication

Key Concepts

• Variation
• Mutation
• Types of mutation
• Point and frameshift mutations
• Chromosomal Mutations

Introduction: 

Variation can arise due to a number of factors that include: 

1. New genetic combinations during meiosis. 
2. Errors occurring during replication. 
3. Mutations caused by environmental factors. 

DNA replication is a process by which DNA produces two identical replicas of itself during cell division. It is an essential part of biological inheritance and occurs in all living organisms.  

Every day millions of cells divide and replicate their DNA’s. This process of replication is generally a fool-proof process. However, sometimes errors occur in this process.  

DNA is a highly stable molecule, and it replicates with high accuracy still changes in DNA structures do occur as a result of errors during replication. These errors are known as mutations. 

 In simple terms, mutation can be defined as a change in the DNA sequence. 

As a result, mutations can produce a new phenotype or alterations in the functions of certain proteins. These alterations can lead to genetic variation within species.  

Mutations can sometimes be inherited and passed on to the next generation. Not all mutations are inherited. 

Explanation: 

Mutations: good or bad? 

Imagine if the DNA sequence of a sperm or egg cell changes. If that sperm or egg cell results in fertilization, then the change in sequence would become part of the offspring. The mutation could result in a protein that does not work correctly, and the offspring may not survive.  

The mutation disrupts the normal activity of genes, and cancer is a good example that states how mutations can cause harmful effects. One such example is cancer. Cancer is caused by the mutations that occur in various growth-controlling genes. It is the most common genetic disorder in humans. 

However, sometimes a mutation is helpful. The mutation may produce a new trait. Maybe the mutation results in the ability to see farther or run faster. As a result of this mutation, the offspring may survive better in its environment. Further, it can pass this new trait to its own offspring. 

This proves that mutations can have a positive effect as well. For example, in sickle cell anemia, the gene that instructs the building of a protein called haemoglobin is mutated.  

As a result, the RBC’s become an abnormal, rigid, sickle shape. However, this mutation also protects against malaria in the African population. 

Types of mutations: 

Mutations can be classified into two types: 

Germline mutations are mutations that occur in the gametes of an organism. These mutations are especially significant as mutations occur in gametes, and gametes are involved in the formation of a zygote which further forms an embryo. As a result, these mutations can be transmitted from one generation to the next, and every cell in the offspring will have that mutation. 

Somatic mutations are the mutations that occur in the somatic cells of the body. These mutations do not have a large effect on the organism because they are restricted to just one cell. These mutations are not heritable. Depending on the mutation, it may or may not cause health problems. 

Mutations can occur at the genetic level or at the chromosomal level. 

The mutations that occur in a gene or DNA are called genetic mutations. 

Mutations occur in two different ways at the DNA level 

1. Point mutations. 
2. Frameshift mutations. 

Point mutations. 

A point mutation occurs when there is a change in a single nucleotide in DNA. If the DNA sequence A-A-G U-U-U-G-G-C is mutated to A-A-G-U-U-U-A-G-C, then the amino acid chain is made with serine instead of glycine. This occurs as a result of substitution. 

Consider these two sentences. The letter “T” is replaced by “R”. 

THE DOG BIT THE CAT 

THE DOG BIT THE CAR  

As you can see, it changes the meaning of the whole sentence. A point mutation is similar to a letter change in a sentence. 

Sickle cell anemia is an example of a point substitution that affects the final protein. Valine is produced instead of glutamic acid as a result of point substitution. When two copies of this mutation are present, it results in a deformity in the red blood cells, i.e., sickle-shaped blood cells are produced and affect the oxygen-carrying capacity. 

Frameshift mutations:  

A frameshift mutation happens when one or more nitrogenous bases are deleted or added. The name frameshift mutations are because the group-of-three reading frame is shifted along the DNA strand. 

Consider the previous sentence as an example,  

THE DOG BIT THE CAT 

THE DOB ITT HEC AT  

(Deleted base (G)) 

THE DOC GBI TTH ECA T  

(Added base (C) It shifts the reading of the codon by one base. 

It shifts the reading frame by one base. A frameshift mutation is usually more harmful to an organism than a point mutation. 

Frameshift mutations are of two types: 

Insertion mutations: One or more nucleotides are added to the base sequence of the nucleic acid, causing a change in the reading frame. 

Deletion mutations: One or more nucleotides are deleted in a nucleic acid, altering the reading frame. Deletion is more common in a frameshift mutation. 

This altered DNA sequence of a protein may be non-usable or form an entirely new protein. This could disrupt various biochemical processes. A frameshift mutation can produce a stop codon in some cases, which results in an abnormally short or long protein product that is non-functional. 

Examples of frameshift mutations include Crohn’s disease, cystic fibrosis, and certain types of cancer. 

Chromosomal mutations: 

Chromosomal mutations cause changes in the chromosomal structure or the loss or gain of a chromosome or a part of a chromosome. 

Chromosomal mutations occur at the time of cell division, crossing over, or fertilization due to certain accidents or irregularities in the chromosomes. These accidents cause a change in the structure and number of chromosomes. 

Sometimes parts of the chromosomes break off during mitosis or meiosis. The pieces may join to the wrong chromosomes, join backwards, or join in the wrong places. Occasionally the broken pieces get lost. These structural changes in chromosomes are called chromosomal mutations. 

Abnormalities in the function of the cell and organism are caused due to chromosomal mutations, as chromosomal mutations can result in abnormal gene numbers or positions.  

These mutations are known to various genetic diseases that can be inherited and are transferred from one generation to the next. 

Chromosomal mutations are more common in plants than animals. Only a few chromosomal mutations are passed on because the fertilized egg usually does not survive. If the organism does develop, it is often not able to reproduce, so the mutation is not passed on. 

Chromosomal mutations include structural mutations which occur as a result of changes in the structure of the chromosomes. Structural mutations are then divided into various types depending on the mechanism: 

• Deletion is a type of structural mutation in which a piece of a chromosome is lost due to breakage. 
• If a piece of a chromosome is deleted, it cannot revert back to normal and, if it is transmitted to the next generation, it can be hereditary. Deletion can either be terminal or intercalary. In terminal deletion, the terminal part of a chromosome is lost and causes a single break in the chromosome. In intercalary deletion, an intermediate section of the chromosome is lost. This involves two breaks on either end of the deleted section. 
• Duplication is a type of structural mutation in which a part of a chromosome is duplicated or present in excess of the normal composition. The genes present might exist in more than two copies as a result of duplication. Some cancers are caused as a result of duplication. 
• Translocation is a type of structural mutation in which a piece of one chromosome breaks off and reattaches to a nonhomologous chromosome. This only involves the rearrangement of a chromosome as there is no net gain or loss of chromosomes. 
• Inversion is a type of structural mutation where a part of a chromosome breaks off, flips and rotates 180° and reattaches to the chromosome. There is no net loss or gain of genes in this type of mutation. Only rearrangement of genes takes place. 

Some chromosomal mutations are caused by changes in the number of chromosomes in a cell. The alteration in the number of an entire chromosome is called heteroploidy. 

Heteroploidy can be divided into two different categories based on changes in either a single whole chromosome or an entire set of chromosomes. 

Aneuploidy involves the loss or addition of one or more chromosomes. An example of aneuploidy is Down’s syndrome. (Trisomy 21) In polyploidy, an organism has more than two sets of genomes. It includes various combinations like triploid, tetraploid, pentaploid, hexaploid and octoploid. 

Summary:

• Variation can also result due to errors that take place during the process of DNA replication.
• DNA replication is an essential part of biological inheritance and occurs in all living organisms.
• DNA is a highly stable molecule, and it replicates with high accuracy; changes in DNA structures and replication errors do occur. These errors are known as mutations.
• Mutation can be defined as a change in the DNA sequence.
• Mutations are inheritable and lead to genetic variation within species.
• Mutations can be classified into two types:
  • Germline mutations: occur in gametes and can be transmitted to offspring.
  • Somatic mutations: occur in the somatic cells of the body. These mutations are not heritable.
• Mutations can occur on gene or chromosomal levels.
• Genetic mutations arising at the gene level are classified as:
  • Point mutations: mutation occurs when there is a change in a single nucleotide in DNA. Sickle cell anemia is an example of a point mutation.
  • Frameshift mutations: occurs when one or more nitrogenous bases are deleted or added, thereby shifting the reading frame. Examples of frameshift mutations include Crohn’s disease, cystic fibrosis, and certain types of cancer.
• During mitosis or meiosis, sometimes the part of a chromosome may break off. This broken piece may join to the wrong chromosomes, join backwards, or join in the wrong places. Occasionally the broken piece can also get lost. These changes in structure are called chromosomal mutations.
• Chromosomal mutations are further divided as:
  • Deletion: loss of a piece of chromosome due to breakage.
  • Duplication: a part of a chromosome is duplicated or present more than the standard composition.
  • Translocation: a piece of one chromosome breaks off and reattaches to a nonhomologous chromosome.
  • Inversion: a part of a chromosome breaks off, flips and rotates 180° and reattaches to the chromosome. No net loss or gain of genes.
• Some chromosomal mutations are caused by changes in the number of chromosomes in a cell and can be divided into two different categories:
  • Aneuploidy involves the loss or addition of one or more chromosomes. An example of aneuploidy is Down’s syndrome.
  • In polyploidy, an organism has more than two sets of genomes.