DNA: The Molecule of Inheritance

BIO 101

Life Science

Dr. D. L. Daley

What are genes made of?

      By late 1800’s it had been established that genetic information exists in discrete units called genes

      However the makeup of a gene was unknown.

      By early 1900’s studies of dividing cells provided strong evidence that genes are parts of chromosomes observed during cell division

      Chromosomes were discovered to be composed of protein and DNA

w   Thus one of these substances must carry the heredity blueprint

Transformation in Bacteria

      Frederick Griffith was trying to make a vaccine to prevent bacterial pneumonia

      He injected a non virulent strain of bacteria & virulent strain - got expected results

      He injected heat killed strain of virulent bacteria - no effect on the mice

      Unfortunately the non virulent or heat killed virulent strain did not produce immunity against the virulent strain

      However when he mixed a heat killed virulent strain with non virulent strain the mice died - a substance from the heat killed strain was transferred to the non virulent strain and made it virulent

DNA

      The molecule of heredity

      A variety of experiments with bacteria and viruses showed that the DNA and not the protein found in chromosomes was responsible for heredity

      Even with the knowledge of the existence of DNA many questions were left unanswered

w   How does DNA encode genetic information?

w   How is DNA duplicated so that information can be accurately passed from one cell to its daughter cells

Structure of DNA

      The secrets of DNA and thus heredity are found in the 3 dimensional structure of  the DNA molecule

      DNA is composed of subunits called nucleotides

      Nucleotides of DNA are composed of

w   A phosphate group

w   A sugar called deoxyribose

w   One of 4 nitrogen containing bases - adenine, guanine, thymine or cytosine

w   In the 1940’s Chargaff discovered that the amount of thymine and adenine is the same in all species as is the amount of guanine and cytosine

DNA is a Double Helix

      In the late 1940’s British researchers, Wilkinson and Franklin began to investigate the structure of DNA with X-ray diffraction

w   DNA molecules were bombarded with x-rays and how the x-rays bounced off allowed them to begin to reconstruct the shape of a DNA molecule

      Wilkinson and Franklin found that the DNA molecule was:

w   Long and thin with a uniform diameter

w   Helical, that is twisted like a corkscrew

w   A molecule of repeating subunits

Watson and Crick Model of DNA

      Combining Wilkinson’s and Franklin’s x-ray diffraction data with a knowledge of how organic molecules bond together and an intuition that “important biological objects come in pairs” allowed James Watson and Francis Crick to propose a model for the structure of DNA

      The model was called the “Double Helix”

      Thus DNA was composed of two separate polymers of nucleotides called strands

Watson and Crick Model of DNA

      Within each strand, the phosphate groups of one nucleotide bonds to the sugar of another nucleotide producing a “backbone”

      The bases extend from the sugar-phosphate “backbone”

      All nucleotides of a single strand are oriented in the same direction

      Therefore the two ends of DNA are different, one end has free or unbonded sugar and the other end has free or unbonded phosphate

Watson and Crick Model of DNA

      Hydrogen bonds hold the DNA strands together by holding the protruding bases from each strand together

w    Interestingly adenine only bonds to thymine and cytosine only bonds to guanine

w    Called complimentary base pairing

      Thus DNA molecule has a ladder-like structure with sugar-phosphate backbones on the outside (the uprights of a ladder)

      The nucleotide bases then form the rungs of the DNA ladder

      The DNA strands are not straight but twisted about each other forming a “double helix”

DNA Structure Movie

 

 

 

 

How does DNA Encode Information?

       The answer of how DNA can code for the color of a bird’s feathers or your eyes is not in the number of different subunits but rather their sequence

       DNA has four different bases that can be arranged in any order, and the sequence of those bases is what encodes the genetic information

       An analogy that is commonly use is that the English language is composed of only 26 letter, Hawaiian only has 12 and the binary language of computer uses only 0 and 1 or on and off.

       Yet all three languages can spell out thousands of different words

       A organism can have millions (bacteria) to billions (plants and animals) of nucleotides in it’s DNA and thus can encode a staggering amount of information

How does DNA Encode Information?

      For words in the English language to make sense, the words must have the correct letters in the correct sequence

      This is also true for genes - the correct bases must be in the correct sequence

Replication of DNA

      All the cells of an organism’s body are the offspring of other cells and can be traced back to a fertilized egg

      Moreover nearly every cell of an organism contains identical genetic information - the same genetic information present in the fertilized egg

      In order to accomplish this, cells starting with the fertilized egg, must reproduce where a parent cell divides in half and forms two identical daughter cells

Replication of DNA

      Thus the parent cell must synthesize an identical copy of its DNA so that each daughter cell has the same compliment of DNA as the original parent cell

w    Process is called DNA replication

      Watson and Crick also suggested that specific base paring - now called complimentary base pairing suggested a possible copying mechanism for the genetic material

      Therefore each strand can act as template for the other strand during DNA replication

w    Thus if one strand read ATG, the other strand will be TAC

DNA Replication

      Enzymes called DNA helicases pull apart the parent DNA double helix - now the bases are no longer paired from the two strands

      Now DNA strands complimentary to the two parent strands must be synthesized

      DNA polymerases move along each separated parent strand - matching bases on the parent strand with free nucleotides, that were previously synthesized in the cytoplasm of the cell

      Thus each new double helix of DNA is part old and part new

w    Called semiconservative replication

      Eventually during cell division a half-old and half-new DNA double helix is delivered to each daughter cell

DNA Replication Movie

 

 

 

 

 

Accurate Replication & Proofreading

      DNA replication is highly accurate but mistakes do happen

      DNA polymerase matches bases incorrectly about one in in every 1000 to 100,000 base pairs

w    This occurs partly because replication is so fast (50 base pairs per second in humans ands up to 1000 base pairs per second in bacteria)

      Completed DNA strands contain about one mistake in every 100 million to 1 billion base pairs - less than one per chromosome in humans

      This phenomenally low error rate is due to a variety of DNA repair enzyme that proofread each daughter strand

      Some forms of DNA polymerase recognize a base pair-pairing mistake as it is made - the enzyme pauses and fixes the mistake and then continues synthesizing more DNA

DNA Synthesis Errors - Mutations