Lecture 07: Lecture 07: Discovery and Significance of CodonDiscovery and Significance of Codon

1. Discovery 1. Discovery

Nobel Prize WinnerNobel Prize Winner

Marshall W. Nirenberg.

He was awarded Nobel

Prize in Physiology or M

edicine in 1968.

For his great contribution

to genetic code.

The World-famous Genetic CodenThe World-famous Genetic Coden

MW Nirenberg; during: 60-68DeWitt Stetten Jr’s LaboratoryUS.NIH in Maryland

Bethesda, MarylandBethesda, Maryland

Two Young MenTwo Young Men In 1959, M Nirenberg, a postdoctoral

fellow at “National Institute of Arthritis, Metabolism, and Digestive Diseases” of the National Institutes of Health (NIH) in Maryland, began his investigations into the relationship between DNA, RNA and the production of proteins.

With Heinrich J. Matthaei, a young post doctoral researcher from Bonn, Germany, he initiated a series of experiments using synthetic RNA.

These two researchers were able to show how RNA transmits the messages that are encoded in DNA and direct how amino acids combine to make proteins.

Unintentional Positive OutcomesUnintentional Positive Outcomes

These experiments

became the foundation of

Nirenberg's ground

breaking work on the

genetic code, which he

first made public at the

International Congress of

Biochemistry in Moscow

in August 1961.

Follow up the VictoryFollow up the Victory By early 1962, the

significance of these early experiments was recognized throughout the world, after the popular media highlighted the importance of their work as a major scientific breakthrough.

His Nobel LectureHis Nobel Lecture

2. Winner’s life2. Winner’s life

He was a New YorkerHe was a New Yorker

Marshall Warren Nirenberg was born April 10, 1927, in New York City, to Harry Nirenberg and Minerva Bykowsky Nirenberg.

In 1941, Marshall developed rheumatic fever, and the Nirenberg family moved to Orlando, Florida, to take advantage of the subtropical climate.

Natural ParadiseNatural Paradise During his teens, Nirenberg developed

a scientific and aesthetic appreciation for the natural world. Reminiscing for his childhood, he remarked in 1992 that "Florida was a natural paradise in those days. And I was the kind of kid who was happy exploring swamps and caves, and collecting spiders." In the Documents section, viewers can see a sketch of spiders that he made when he was 17 years old.

The Bachelor & Master DegreesThe Bachelor & Master Degrees

In 1945, Nirenberg graduated from high school and enrolled at the University of Florida in Gainesville. He earned his B.S. degree in zoology and chemistry in 1948.

In 1950, he resumed his studies at Florida and took a M.S. degree in zoology in 1952, writing a master‘s thesis on caddis fly.

His Doctorate ProgramHis Doctorate Program

Later in 1952, Nirenberg moved to Ann Arbor to attend the University of Michigan.

In 1957, Nirenberg earned a Ph.D. in biological chemistry by writing a dissertation on the uptake of hexose (己糖 ), a type of sugar, by tumor cells.

This work served as the basis of his first published article and shaped the direction of his initial studies after graduate school.

Postdoctoral WorkPostdoctoral Work In 1957, the American Cancer Society

awarded Nirenberg a two-year postdoctoral fellowship to DeWitt Stetten, Jr.'s laboratory at the “National Institute of Arthritis, Metabolism, and Digestive Diseases (NIAMDD)”, a part of the National Institutes of Health (NIH) in Bethesda, Maryland.

In 1959, Nirenberg was chosen as a postdoctoral

fellow of the Public Health Service's Section on

Metabolic Enzymes at NIAMDD.

The following year, Nirenberg joined the staff as a

research biochemist.

World Reached out Hands to HimWorld Reached out Hands to Him In 1962, less than one year after he

had first announced his successful experiment with synthetic RNA, he received the Molecular Biology Award from the National Academy of Sciences.

During this same period, Nirenberg was offered professorships at a number of major universities across the United States.

Nirenberg, however, declined all offers and chose to stay at the National Institutes of Health.

In 1962, he was appointed Chief of the Section on Biochemical Genetics at the NIH's National Heart Institute (NHI).

The Supremacy Honor of ScienceThe Supremacy Honor of Science

After Matthaei's departure from the NIH in 1962, Nirenberg continued his work on the genetic code with a team of postdoctoral fellows and research technicians.

By 1966, Nirenberg had deciphered all the RNA "codons"--the term used to describe the "code words" of messenger RNA--for all twenty major amino acids.

Two years later, in 1968, Nirenberg received the Nobel Prize in Physiology or Medicine for "interpretation of the genetic code and its function in protein synthesis."

He shared the award with Robert W. Holley of Cornell University and Har Gobind Khorana of the University of Wisconsin at Madison.

R. Holley H.G. Khorana M. Nirenberg

H. Gobind Khorana(46y) How to synthesize triplet RNA

Marshall Nirenberg(41y) Genetic coden

Robert Holley(46y) tRNAphe cloverleaf structure

Like-minded partnerLike-minded partner

1961 --Marries Perola Zaltzman (2001) in July

Brief ChronologyBrief Chronology 1927 --Born Marshall Warren Nirenberg in New York, New York (April 10) 1941 --Nirenberg family moves to Orlando, Florida 1948 --Receives B.S. (Zoology and Chemistry), University of Florida at Gainesville 1952 --Receives M.S. (Zoology), University of Florida 1957 --Receives Ph.D. (Biological Chemistry), University of Michigan at Ann Arbor 1957-59 --American Cancer Society Postdoctoral Fellow, National Institute of Arthritis, Metabolic, and Digestive Diseases [NIAMDD, later NIDDK], National Institutes of Health [NIH] 1959-60 --Public Health Service Postdoctoral Fellow, NIAMDD 1960-62 --Research Biochemist, NIAMDD; begins poly-U experiments with Heinrich J. Matthaei 1961 --Marries Perola Zaltzman (d. 2001) in July 1961 --Describes the poly-U experiment at International Congress of Biochemistry in Moscow in August 1962 --Molecular Biology Award, National Academy of Sciences 1962-66 --Chief, Section on Biochemical Genetics, National Heart Institute [NHI], NIH 1963-66 --Completes sequencing of RNA "code words" for twenty amino acids 1965-69 --Turns attention and laboratory over to field of neurobiology 1966 --Senior Research Biochemist and Chief, Laboratory of Biochemical Genetics, NHI 1966 --Awarded National Medal of Science by President Lyndon B. Johnson 1967 --Begins studying the neuroblastoma system 1968 --Shares Nobel Prize in Physiology or Medicine for deciphering the genetic code with Robert W. Holley and Har Gobind Khorana 1968 --Awarded National Medal of Honor by President Lyndon B. Johnson 1969 --Publishes first article on neurobiology in collaboration with Philip Nelson 1973 --Begins studying the effects of morphine on the nervous system in collaboration with Werner Klee 1976 --Begins work on neural cell receptors using chick retina 1989 --Begins study of Homeobox genes in Drosophila fruit fly 2001 --Elected to American Philosophical Society

3. The function of 3. The function of CondonCondon

Section P Section P Genetic code and tRNAGenetic code and tRNA

P1 The genetic code

P2 tRNA structure and

function

P1 The genetic codeP1 The genetic code

Nature Deciphering Feature Effect of Mutation Universality ORFs Overlapping Genes

Thanks!