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DNA: Discovery, Facts, Structure & Function in Heredity

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Lesson Transcript
Instructor: Greg Chin
This lesson will help you to navigate the twists and turns of DNA's structure. We'll also clue you in on the amazing discoveries that put this nucleic acid in the limelight as the molecule of heredity.

Nitrogenous Bases Review

Previously, on 'DNA and RNA':

'…but we'll also reveal the identity of the true killer of our poor departed Mr. Bones.'

'…but there are four different nitrogenous bases: guanine, adenine, thymine and cytosine.'

'You see, cytosine can form three hydrogen bonds with guanine, and adenine can form two hydrogen bonds with thymine.'

'If we represent the strands as arrows, with the arrowhead at the three prime end of the strand, we can see that the strands in a DNA molecule are organized antiparallel relative to each other.'

Discovery of the Transforming Principle

Miss Ivory: Objection! How do we even know that what he's saying is true? Professor, you say that deoxyribonucleic acid, or DNA, is the recipe for life, but how do we know you aren't just throwing around your fancy science word in a big smokescreen to clear the accused, Colonel Custard, of this crime? Can you offer proof that DNA is the molecule responsible for transmitting heritable traits in organisms? Answer me that?

Professor Pear: Oh, yes. I certainly can! There's lots of evidence, but let me just summarize the work of Frederick Griffith and Oswald Avery. Their labs provided strong evidence that DNA is the molecule of heredity. Griffith was studying the bacterium that causes pneumonia. He observed two variants of the same bacteria under the microscope. One had a smooth outer appearance. Let's abbreviate those bacteria as 'S bacteria.' The other had a rough appearance. Let's abbreviate those bacteria as 'R bacteria.'

If he injected a mouse with S bacteria, the mouse died. If he injected a mouse with R bacteria, the mouse lived. We would later discover that the S bacterium is smooth because it has a protective coating, which helped it survive in the mouse; whereas, the R bacterium lacked a coating and was susceptible to the mouse's immune system. If Griffith heated the S or R bacteria, it killed the bacteria. Not surprisingly, a mouse injected with the dead bacterial parts did not die. Oddly though, if he mixed dead cell parts from S bacteria with living R bacteria and injected a mouse, the mouse died! Isn't that peculiar? But that's not all.

When he examined the dead mouse more closely, he found S bacteria, not R, inside the corpse! Somehow the R bacteria had transformed into S bacteria. This transformation was permanent, meaning it was a trait that was inherited from generation to generation. Using the mysterious new S bacteria from the dead mouse in a new injection experiment also produced a dead mouse. That meant that the R bacteria had permanently been changed into S bacteria.

DNA is the Molecule of Heredity

Oswald Avery dubbed Griffith's mysterious substance that transformed the R bacteria into S bacteria as the 'transforming principle'. He decided he and his lab would determine the identity of this substance.

I should probably provide a little context for this time in scientific history. At the time of Avery's experiments, most scientists believed DNA to be uninteresting compared to proteins and less complex than even carbohydrates or lipids. For instance, there were twenty known amino acids but only four types of DNA nucleotides. Surely a molecule of such simple complexity couldn't be the molecule of heredity.

Avery spent many years purifying the transforming principle, and then tried to characterize which type of molecule was responsible for transforming R bacteria into S bacteria. To identify the molecule that could transform the R bacteria into S bacteria, Avery and his team devised a series of clever experiments. By spinning the purified sample very fast in a machine, known as a centrifuge, fats were eliminated from the sample. Sample treated in this manner could still transform R cells into S cells.

Shockingly, treating the sample with something that degrades protein did not affect the ability of the purified sample to turn R cells into S cells. Treating the sample with a substance that degrades RNA also did not affect the transforming principle. However, treating the purified sample with something that degraded DNA eliminated the R to S transformation.

Spinning the bacteria in a centrifuge did not stop transformation
Centrifuge

Avery concluded that the transforming principle was DNA. Today, we know that permanently changing the characteristics of an organism can be accomplished by changing its DNA content.

Discovery of the Double-Helix Structure

Miss Ivory: Well, what about your assertion that you know the structure of DNA? You, yourself, said that it's a microscopic molecule found inside a cell. If that is true, how can you possibly know what it looks like?

Professor Pear: Oh, actually that's another fascinating story. James Watson and Francis Crick devised a model of the structure of DNA based on the evidence produced by several different laboratories at the time. Examining X-ray images of DNA revealed that the molecule had a helical, or spiral, shape. Data from another lab indicated that there is a one-to-one ratio between adenine and thymine. The lab also demonstrated that there is a one-to-one ratio between guanine and cytosine. By using cardboard cutouts of the bases, Watson realized that two hydrogen bonds could form between A and T and three hydrogen bonds could form between G and C.

Interestingly, Watson originally predicted there were only two hydrogen bonds between G and C, but we know now that there are three. Even a Nobel Prize-winning scientist is wrong sometimes! In order to reconcile the X-ray data and Watson's model of the ratio between bases, Crick realized that the DNA strands had to be oriented antiparallel to one another. This led the two of them to postulate the famous double-helix structure of DNA.

A helix is a cylindrical spiral. A double-helix is basically just two cylindrical spirals. Picture DNA as a ladder with backbones made of phosphate groups and sugars and rungs of nitrogenous bases held together by hydrogen bonds. Then, twist the ladder around an imaginary central axis. The structure of the molecule looks a little like a spiral staircase, not unlike the one on which the body of the victim was discovered.

The helix and double-helix DNA structures
Helix Double Helix Image

James Watson, Francis Crick and another scientist named Maurice Wilkins were awarded the 1962 Nobel Prize in Physiology or Medicine for 'their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material.'

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