Gene Mutation and Protein Variants

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The sequence of bases in DNA codes for the amino acid sequence (primary structure) of a protein. 

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 The primary structure of the protein determines secondary structure and tertiary structure .... and thus SHAPE.
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Click here to review the page		 The SHAPE of the protein enables it to fit with a ligand and perform its FUNCTION.

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Soooooo  ..........  the base sequence of the DNA ultimately determines the SHAPE and FUNCTION of the protein.

The "normal" base sequence (wild type allele) will be "read out" to produce a protein with "normal" shape and function (wild type protein).

Because the protein has "normal" function, the  cell will be "normal" or wild type (have the wild phenotype).

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   .............. DNA is only a chemical - and it can be damaged easily. What happens if the DNA molecule is damaged?   Then we would have a changed sequence!
 
 

ORIGINAL SEQUENCE: ATGCCATGAGATGCG Wild Type Allele
CHANGED SEQUENCE:  ATGCCGTGAGATGCG Mutant Allele

So we can have 2 versions of the gene .........  these are called alleles of the gene.  In this case we have the wild type allele (the "normal" version found in wild populations) and a mutant allele (the changed version).
 
 
 

......... in fact we can have many mutant alleles because a gene may be several hundred bases long ....... and any base can be changed to any of 3 others!


 
 

Three ways to mutate a gene.

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Base Substitution. 

This example shows what happens if the 4th base is changed or if the 11th base is changed.  These changes would each produce a different mutant allele (b-1 or b-2).

  1. A single base is deleted, but another base is added.  This results in the same number of bases in the sequence.
  1. The substitution of one base for another codes for a different amino acid.  The result is a change in a single amino acid in the protein sequence.
  1. The changed amino acid sequence resulting from the gene mutation produces a variant of the protein!
+1 Frameshift (Base Addition). 

This example shows what happens if a new base is added after the 5th base or the 11th base, but no bases are removed. 

  1. A single base is added, but another base is not deleted.  The result is  1 additional base in the sequence.
  1. The addition of one base for another shifts the "reading frame". 
    • The amino acid at the point of the mutation is changed.
    • Because of the shift in the reading frame, all the other amino acids from the point of the mutation onward, are also changed!
-1 Frameshift (Base Deletion). 

This example shows what happens if the 5th base or the 11th base is removed,  but no bases are added. 

  1. A single base is deleted, but another base is not added.  The result is  1 less base in the sequence.
  1. The deletion of one base for another shifts the "reading frame". 
    • The amino acid at the point of the mutation is changed.
    • Because of the shift in the reading frame, all the other amino acids from the point of the mutation onward, are also changed!

 


If a mutation occurs in the DNA of the gene what is the effect on the protein it codes for ?

 
 

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  1. The change in base sequence of the DNA will be transcribed - and result in a change to  the base sequence of the messenger RNA.
  2. The change in the base sequence of the mRNA will be translated - and result in a changed amino acid sequence.
  3. The changed sequence of amino acids in the variant of this protein will fold up incorrectly - and result in a changed secondary structure.
  4. The changed secondary structure results in a changed tertiary structure - an incorrect SHAPE.
  5. The incorrect SHAPE may result in a loss of FUNCTION.
 
FOR EXAMPLE:   The shape of the active site of an enzyme must be complementary to the shape of the substrate molecule.  This enables, the substrate to fit into the active site;  as a result the enzyme catalyzes a biochemical reaction.  If the shape is changed, the substrate no longer fits in and the enzyme loses its function!

 
 
 
  • The loss of PROTEIN FUNCTION as a result of GENE MUTATION is the basis of GENETIC DISEASE !!!!!
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