DNA: History of discovery of its Structure & Function

DNA Structure & Function How do genes work? What are they made of? How do they determine characteristics of organisms? In the middle of the 1900s, questions like these were on the minds of biologists everywhere.

Griffith and Transformation 1928: British scientist Frederick Griffith was trying to figure out how bacteria make people sick. Griffith wanted to learn how certain types of bacteria produce a serious lung infection known as pneumonia.

Frederick Griffith

What did he do? isolated two slightly different strains of pneumonia bacteria from mice Both strains grew very well, but only one of the strains caused pneumonia. disease-causing strain of bacteria = smooth colonies harmless strain = colonies with rough edges

Griffith's Experiments injected mice with the S bacteria  pneumonia and died. mice injected with R bacteria  totally healthy. Griffith wondered if the disease-causing bacteria might produce a poison.

Heat killed S bacteria into mice  Healthy mice! The mice survived, suggesting that the cause of pneumonia was not a chemical poison released by the disease-causing bacteria. Heat killed S bacteria + R bacteria in mice  DEAD mice! He found their lungs filled with the deadly S bacteria. Some factor from the dead bacteria had “transformed” the harmless bacteria into disease-causing ones.

Transformation  process in which one strain of bacteria is changed by a gene or genes from another strain of bacteria Griffith hypothesized since the ability to cause disease was inherited by the transformed bacteria's offspring, the transforming factor might be a gene (genetic material)

Although Griffith made a great discovery, he did not follow through and figure out what actually transformed the bacteria.  Avery came along and did that.

Avery and DNA 1944, a group of scientists led by Canadian biologist Oswald Avery at the Rockefeller Institute in New York decided to repeat Griffith's work. to determine which molecule was the genetic material responsible for transformation.

Oswald Avery

Avery’s experiment Made an extract from the heat killed bacteria Used enzymes that destroy the lipids, carbohydrates, proteins, and RNA. Transformation still occurred. Used DNA destroying enzyme. Transformation did NOT occur. DNA must be the genetic material. Avery and other scientists discovered that the nucleic acid DNA stores and transmits the genetic information from one generation of an organism to the next.

Scientists are skeptical. Scientists don’t always believe things with proof from only one experiment… So other scientists set out to prove what the genetic/hereditary information of an organism is.

Hershey & Chase Alfred Hershey and Martha Chase 1952, American scientists Studied viruses (non living particles)

Martha Chase and Alfred Hershey

The Hershey-Chase Experiment Used bacteriophages (virus that infects bacteria) composed of a DNA or RNA core and a protein coat When a bacteriophage attacks a bacterium, it injects its genetic information into the bacterium. Those genes take over the cell, producing many new viruses.

Bacteriophage

Nucleic Acid or protein?? They wanted to find out which part of the phage (DNA or protein), produced new phages. Grew bacteriophages with radioactive markers phosphorus-32 (32P) only in DNA sulfur-35 (35S) only in Protein

mixed the marked viruses with bacteria waited a few minutes for the viruses to inject their genetic material. separated the viruses from the bacteria and tested the bacteria for radioactivity. Nearly all the radioactivity in the bacteria was from phosphorus (32P), the marker found in DNA.

Hershey and Chase concluded that the genetic material of the bacteriophage was DNA, not protein.

The Components and Structure of DNA

DNA components DNA is a long molecule made up of units called nucleotides. Nucleotides are made up of three basic components: 5-carbon sugar (deoxyribose) a phosphate group a nitrogenous base 4 kind of nitrogen bases found in DNA adenine (A), guanine (G) = double ringed (purines) cytosine (C), thymine (T) = single ringed (pyrimidines)

DNA structure backbone of a DNA chain = sugar and phosphate groups of each nucleotide. The nitrogenous bases stick out sideways from the chain. The nucleotides can be joined together in any order any sequence of bases is possible. With 4 bases – millions of different combinations are possible

DNA

Erwin Chargaff American biochemist, 1940s discovered that the percentages of guanine [G] and cytosine [C] bases are almost equal in any sample of DNA Later found that [A] = [T] Scientists had NO idea what this was…

Chargaff's Rules 

Franklin & Wilkins British scientists, 1952 used a technique called X-ray diffraction to get information about the structure of the DNA molecule X-shaped pattern shows that the strands in DNA are twisted around each other like the coils of a spring a shape known as a helix the X suggests that there are two strands in the structure Other clues suggest that the nitrogenous bases are near the center of the molecule

Franklin Wilkins X-shaped DNA (from X-ray Diffraction

X-ray crystallography How did they (and others) do it??? X-ray crystallography Showed that the DNA molecule is a helix

Watson & Crick Francis Crick, a British physicist & James Watson, an American biologist trying to understand the structure of DNA by building three-dimensional models of the molecule 1953, they are shown a picture of Franklin’s x-ray and immediately knew the structure Watson and Crick's model of DNA was a double helix, in which two strands were wound around each other.

Double Helix Twisted ladder or spiral staircase realized that the double helix accounted for many of the features in Franklin's X-ray pattern did not explain what forces held the two strands together. discovered that hydrogen bonds could form between certain nitrogenous bases and provide just enough force to hold the two strands together

Base Pairing hydrogen bonds can form only between certain base pairs adenine (A) with thymine (T) guanine (G) with cytosine (C)