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The History of Molecular Genetics The early contributions: setting the stage Gregor Mendel: mid 1800’s Gregor Mendel By studying pea plants, determined: – Characteristics are inherited in discrete units (later called genes) – Inherited units are independently segregated and assorted – Inherited units can be dominant or recessive The early contributions: setting the stage Thomas Hunt Morgan: early 1900’s – Worked at Columbia University; later at CalTech – Studied fruit fly eye color, determining that trait was sex-linked – Won the Nobel Prize in 1933 for his work on chromosomes and genetics Thomas Hunt Morgan The early contributions: setting the stage By this point, it was known that genetic material was located on a chromosome This genetic material was in discrete units called genes It was NOT known whether the gene was simply a protein, or whether it was composed of DNA Frederick Griffith Late 1920’s From Britain Worked with bacteria called Streptococcus pneumoniae Defined the term, “TRANSFORMATION” Frederick Griffith: the transforming principle Transformation Change in a genotype and phenotype due to the incorporation of external DNA by a cell How did Griffith know that the dead mouse was killed by transformed bacteria? Transformation The dead mouse had living virulent bacteria in its blood Oswald Avery American biologist and physician – Born in Canada, but grew up in NYC Worked in the 1930’s – 1950’s Also worked with the transformation principle Colleagues—McCarty and MacLeod Oswald Avery Avery’s work involved separating DNA and proteins, and then attempting to see which substance could transform live, nonpathogenic bacteria into pathogenic bacteria Oswald Avery Avery’s conclusion: – DNA is the transforming substance However……most scientists at the time still believed that the transforming substance was a protein Hershey and Chase Alfred Hershey; Martha Chase Early 1950’s Used phages – Viruses used to infect bacteria – Called “T2” phages Their question: which part of the virus—protein coat or DNA—in responsible for transforming E. coli ? Hershey and Chase T2 PHAGE Hershey and Chase Experiment Hershey and Chase Conclusion: – DNA IS RESPONSIBLE FOR TRANSFORMATION OF BACTERIA, NOT PROTEINS – THEREFORE, DNA IS THE HEREDITARY MATERIAL Erwin Chargaff Biochemist Died in 2002 Worked at Columbia University since 1950’s Studied proportion of purines and pyrimidines in DNA Erwin Chargaff Findings: CHARGAFF’S RULES – DNA composition varies between different species – In a given species, the four nitrogen bases are present in a predictable ratio Chargaff’s Rules Human DNA: – – – – A = 30.9% T = 29.4% G = 19.9% C = 19.8% A = T; G = C Chargaff couldn’t explain this, but this information later became crucial to Watson and Crick THE RACE IS ON! Who discovers the double helix? Linus Pauling Worked at CalTech Died in 1994 – Won Nobel prize in chemistry in 1954 for work in chemical bonding; Nobel peace prize in 1962 for his campaign against above-ground nuclear testing Linus Pauling Linus Pauling He also worked on the structure of DNA, but came up with a TRIPLE HELIX – He thought DNA was 3 strands with the phosphates on the inside Franklin and Wilkins Rosalind Franklin; Maurice Wilkins Worked in London Franklin and Wilkins Used X-ray crystallography to look at the shape of DNA Their information gave Watson and Crick the necessary information they needed to come up with the double helix structure – Width of the helix – Spacing of the nitrogenous bases James Watson and Francis Crick James Watson and Francis Crick Used wire models to conform with the measurements that Franklin and Wilkins had come up with Determined the structure to be a double helix James Watson and Francis Crick Won the Nobel prize in medicine in 1962 for their discovery Maurice Wilkins was also included in winning the Nobel prize – Who was excluded??? Avery, Franklin, Chargaff, Pauling, and about 20+ other scientists who were instrumental in discovering the shape of DNA – Rosalind Franklin had died in 1958; Avery died in 1955 James Watson and Francis Crick James Watson and Francis Crick Crick died in 2004 Watson is still living, though recently forced to resign his administrative job at Cold Spring Harbor labs due to racist statements