Module 7 Lesson 4 - 2

Mutation

Read pages 643 - 644

Mutations are very rare, thanks to many built-in mechanisms that proofread for mistakes in DNA sequence and redundancy in mRNA codons. However, mistakes do happen during DNA replication and result in mutation that can be passed to the next generation. Although we refer to mutation to describe a mistake, mutations are not always undesirable.

Mutation results in genetic variation that can start evolution. It yields new alleles, and sometimes a specific allele can provide an advantage to the survival of the organism. The organism with the mutated allele might be better suited to survive and pass those genes to their offspring.

The structure of DNA is not permanent. It changes constantly. Enzymes such as DNA polymerase repair many changes immediately, but many are missed and not repaired. A permanent change in the DNA is a mutation.

Mutations can occur in two locations:

1. Somatic Cell Mutation: If a mutation occurs in a body cell, the mutation is passed to daughter cells when the cell divides after replication. Therefore, somatic cell mutations affect only the individual organism.
   


2. Germ Line Mutation: When a mutation occurs in the DNA of a gamete cell, the mutation may be passed to the next generation of organisms. Germ line mutations are one way that genetic variation can occur in a population.

Types of Mutation

1. Chromosomal mutations are a type of mutation you studied earlier in this module. These mutations occur when chromosomes cross over and recombine genetic material. Other chromosomal mutations can occur if part of the chromosome is lost or duplicated during DNA replication. Remember that nondisjunction can result in major differences. In nondisjunction, because chromosomes are not segregated correctly, cells can result that have too many (trisomy) or not enough (monosomy) chromosomes.


2. Point mutations occur when the mutation involves a single or a few base pairs in the DNA sequence. It can involve substitution, insertion, or deletion of nucleotides.
   
   
   1. Substitution Substitution occurs when one base pair is exchanged for another base pair. The effect of a substitution depends on the actual nucleotide substituted and the subsequent effect on the protein.
      
      Example A - Silent Mutation
      
      

      	Normal	Mutation
      mRNA	UGC AUA AAU GGC	UGC  AUC AAU GGC
      Amino Acid	Cys - Iso - Asp - Gly	Cys - Iso - Asp - Gly

      C nucleotide was substituted for the A nucleotide in the second codon triplet. Both the original triplet AUA and the mutated triplet AUC code for the same amino acid, isoleucine. This type of mutation in which the protein or amino acid chain is unaffected is called a silent mutation.
      
      Example B - Missense Mutation
      
      

      	Normal	Mutation
      mRNA	UGC AUA AAU GGC	UGC  UUA  AAU GGC
      Amino Acid	Cys - Iso - Asp - Gly	Cys - Leu - Asp - Gly

      The substitution of U for A in the second triplet causes a change in the amino acid coded for this time. This type of mutation is called a missense mutation and can cause the protein not to work or to be less effective. This type of mutation could develop new forms of proteins that might meet other needs.
      
      This is the type of mutation that causes the harmful sickle cell anemia disease. A single nucleotide, A, is substituted to T, which results in valine instead of glutamate amino acid.
      
      
      
      Example C - Nonsense Mutation
      
      

      	Normal	Mutation
      mRNA	AUA UGC AAU GGC	AUA UGA AAU GGC
      Amino Acid	Iso - Cys - Asn - Gly	Iso - STOP  -- --

      Some substitutions such as that in Example C do not allow the protein to function at all. In this example, the amino acid sequence is terminated and the protein is cut short and is non-functioning. This is an example of a nonsense mutation.
   
   
   
   2. Insertion
      
      Insertion occurs when one or more nucleotides are inserted into the DNA sequence.
      
      Example D
      
      

      	Normal	Mutation
      mRNA	UGC AUA AAU GGC	UGC AUG AAA UGG C
      Amino Acid	Cys - Iso - Asp - Gly	Cys - Met - Lys - Trp

      G nucleotide was inserted into the sequence in the second codon triplet. This resulted in a frameshift mutation in which the entire reading frame of the gene is altered by one nucleotide to the right. The frameshift mutation caused missense mutations for the remaining DNA sequences that come after the point mutation location.
   
   
   
   3. Deletion 
      
      Deletion occurs when a single nucleotide or a portion of the DNA sequence is deleted.
      
      Example E
      
      

      	Normal	Mutation
      mRNA	UGC AUA AAU GGC	[U] GCA UAA AUG GC
      Amino Acid	Cys - Iso - Asp - Gly	Ala - STOP -- --

      In this example, the first nucleotide U was deleted from the sequence. This resulted in a frameshift mutation as well. Although the first amino acid was altered to alanine (missense mutation), the second amino acid coded for a stop codon and resulted in an incomplete protein (nonsense mutation).