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