Introduction to Cell & Molecular Biology (BIOL121) - Dr. S.G. Saupe (ssaupe@csbsju.edu); Biology Department, College of St. Benedict/St. John's University, Collegeville, MN 56321

Molecular Evolution of Two Human Sex Hormones
Pre-Class Assignment
  1. Print a copy of this exercise and bring it to class.
  2. On a separate sheet of paper, type a brief description of the function of luteinizing hormone and human chorionic gonadotropin.
 Post-Class Assignment
  1. On a separate sheet of paper, complete the questions and turn it for grading.  Be sure to put your name on both papers
  2. Write a brief explanation of how the β-LH gene evolved into the β-HCG.


Introduction:
    In this exercise we will study the mechanism of evolution of two human genes.  One of the genes is for the production of  luteinizing hormone (LH) which stimulates ovulation in females and testosterone production in males.  The other gene is for human chorionic gonadotropin (HCG), a hormone produced by the early embryo and that serves as the basis of the pregnancy test.

    Both of these hormones are quaternary proteins comprised of 2 chains - an alpha (α) chain and a beta (β) chain.  The α-chains of both hormones are identical and this protein is coded by a gene on chromosome #6. 

     The β-chains of both proteins are similar and are coded by a cluster of eight genes on chromosome 19.  Seven of the genes code for β-HCG and the other one for β-LH.  It is hypothesized that this cluster of genes originally evolved from a single β-LH.  This gene was duplicated accidentally during meiosis.  One of the duplicated β-LH genes was conserved and is our current β-LH gene.  However, the other gene accumulated mutations and evolved into a β-HCG gene.  This β-HCG gene was then duplicated several additional times (for a total of seven genes) resulting in our current arrangement on chromosome 19. 

     This exercise compares the β-HCG and β-LH genes and suggests the process by which the β-LH may have evolved into a β-HCG gene.

Exercise:   
     The first 112 amino acids of the both the β-HCG and β-LH proteins are identical.  These proteins differ only in the amino acids at their terminal end following the first 112 amino acids.  The following represents the nucleotide sequence in the template (or sense) strand of the β-LH gene.  The dots (. . . . ) represent the DNA sequence for the first 112 amino acids.

  1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
..... G G G G T T G A G A G T C C G G A G G A G A A G
                                                 
25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48
  G A G A T T T C T G G G A G G G G C G T C G G A
                                                 
  49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72
  A G G T T C A G G T A G G G C T G A G G A C C T
                                                 
  73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96
  C G G G A C T G T G G G G C T A G G A G G G T G
                                                 
  97 98 99 100 101 102                                    
  T T A T T T                                    


1.  Beneath each nucleotide above, write the nucleotide sequence for the mRNA that will be coded by the terminal segment of the β-LH gene.

2.  Using a codon table, write the amino acid sequence that will be coded by this portion of the β-LH gene.

3.  How many total amino acids are specified by the β-LH gene?  __________

The terminal section of the β-HCG gene differs from the β-LH gene by only 12 nucleotides.  These differences are summarized as follows:

change T @ nucleotide 5 to C
delete T @ nucleotide 6    
change G @ nucleotide 9 to A
change A @ nucleotide 10 to G
change A @ nucleotide 28 to T
change T @ nucleotide 31 to C
change T @ nucleotide 33 to G
change C @ nucleotide 42 to G
change A @ nucleotide 69 to G
change T @ nucleotide 72 to C
add G & C after A @ nucleotide 77    

Thus, the terminal nucleotide sequence for the β-HCG gene, incorporating the changes from the list above (shown in RED), is:

  1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24    
..... G G G G C   G A A G G T C C G G A G G A G A A G    
                                                     
25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48
  G A G T T T C C C G G G A G G G G G G T C G G A    
                                                     
  49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72    
  A G G T T C A G G T A G G G C T G A G G G C C C    
                                                     
  73 74 75 76 77     78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96
  C G G G A G C C T G T G G G G C T A G G A G G G T G
                                                     
  97 98 99 100 101 102                                        
  T T A T T T                                        


4.  Beneath each nucleotide above, write the nucleotide sequence for the mRNA that will be coded by the terminal segment of the β-HCG gene.

5.  Using a codon table, write the amino acid sequence that will be coded by this portion of the β-HCG gene.
 

6.  How many total amino acids are specified by the β-HCG gene?  _________


Reference:
    This article was adapted from the following article:  Offner, S (1994) Using chromosomes to teach evolution.  I.  Conserved genes & gene families.  American Biology Teacher 56: 79 - 85.
 

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Last updated: July 14, 2009     � Copyright by SG Saupe