DNA-double helix, genetic code and genes

Done by: Ensy caroline Farhath Jabien Felly Khin Thiri Han (jewel) Melisa Miao Lin Miao Yan Nishachand vohreh

DNA- Double Helix

Monomer unit : nucleotide Process for forming polynucleotide: condensation 1. Components: Deoxyribose sugar(pentose) Phosphate group Nitrogenous base: Purine and Pyramidine ( A,T,G,C) 2. Structure: Two strands anti parallel. The sugar-phosphate backbones wind around the helix axis like the railing of a spiral staircase.

DNA- Double Helix

3. The bases of the individual nucleotides are on the inside of the helix, stacked like the steps of a spiral staircase. 4. Types of bond: Hydrogen bond Covalent bond Phosphodiester bond Glycosidic bond

Introduction of famous scientists

Erwin Chargaff Chromatography and photospectrometer on DNA Rosalind Franklin & Maurice Wilkins X-ray Diffraction Watson & Crick remodel double helix Gregor mendel, Thomas Morgan, Johanssen &Avery- genes Nirenburg breaking genetic code

ERWIN CHARGAFF

11 August 1905 20 June 2002

Background
Born in Czernowitz (now known as Chernovtsy in Ukraine) on August 11, 1905 Gainned his PhD from the University of Vienna working first in Berlin and then at the Pasteur Institute, Paris. Initially, work in biochemical field, including lipid metabolism and the process of blood coagulation.

What makes his attention became concentrated on DNA molecule?

In 1944, he read a paper by Oswald Avery showing that DNA, not protein, transmitted genetic information. At that time, tetranucleotide hypothesis of DNA by Phoebus Levene was still popular. Levene postulated that DNA may not be the one which carry the genetic information because it only made up of four bases which is repeated over and over in DNA compare to protein which contains 20 amino acids.

Chargaffs Experiment
Supported by two recently developed techniques : paper chromatography and ultraviolet spectrophotometer Steps: 1. Isolated DNA from the nuclei and broke it down into its constituent nuclei acids. 2. Separated the purines and the pyrimidines using paper chromatography.

3. Exposed the separate components of the solution to ultraviolet light

Chargaffs rule (published in 1950)

1. The number of guanine units equals the number of cytosine units and the number of adenine units equals the number of thymine units ( A=T , G=C) 2. The amounts of A, G, T, and C bases are varies from one organism to organism. Such evidence of molecular diversity, which had been presumed absent from DNA, made DNA a more credible candidate for the genetic material than protein.

Rosalind Franklin and Maurice Wilkins

Rosalind Franklin
Rosalind Elsie Franklin was born on 25 July 1920 she was a British biophysicist, physicist, chemist, biologist and X-ray crystallographer who made important contributions to the understanding of the fine molecular structures of DNA, RNA, viruses, coal and graphite. Came to Kings college to join J.T Randalls lab. Her work began on x-ray diffraction of proteins, while fellow scientists Maurice Wilkins and his assistant were working on Pure DNA. She worked independently on DNA samples, refusing to work along with Wilkins.

Maurice Wilkins
Maurice Hugh Frederick Wilkins was born on 15th December 1916. He was a New Zealand molecular biologist and Nobel Laureate who did research on phosphorescence, radar, isotope separation and X-ray diffraction. He used reflecting microscope to work on DNA sample. He discovered that DNA could be drawn into very thin fibres, thus used X-ray diffraction to take photos.

Discovery of double helix

Franklin assembled a new set of X-ray equipment and a camera that had ability to keep humidity constant. She realized DNA had 2 forms: dry-crystalline(A) and very hydrated Para crystal(B). She took a picture of both forms.
Photograph 51(B), which was passed onto Watson and Crick.

Discovery of double helix

Wilkins realized the results were similar to his prediction of helical structure which he came up with along with a physician.

Watson and Crick Biography

Dr. Francis Harry Dr. James Dewey Watson Compton Crick June 8, 1916 April 6, 1928 Northampton, England Chicago, Illinois, USA They met while working at the Cavendish Laboratory at the University of Cambridge. Both wanted to uncover a genes true structure, and in 1953 the two figured out that DNA had to be composed of two double-helical configurations.

Watson and Crick Discovery

The double helix structure known as B-form. Helix diameter 2.34nm. Most common structure

found in living cells.

Two grooves spiral:
Major grooves Minor grooves

Watson and Crick Discovery

Two other conformations:

A-DNA:
shorter and wider form Right-handed

Z-DNA,
Left-handed confirmation. Narrow and deep. Z-DNA is a transient form of DNA, plays an important role in biological role.

The Coding craze

How the nucleotide bases were translated into proteins in the body's cells. After 1953, scientists scrambled to be the first to decipher the genetic code. Problem: how many bases would be in each code word (later known as a codon).

The Coding craze

There is a total of four bases guanine, cytosine, adenine, and thymine. Assume: 2 bases = (4X4 = 16 amino acids) But there were 20 known amino acids 3 bases = (4x4x4 = 64 amino acids) The genetic code must use blocks of at least three RNA bases to specify each amino acid Mystery remained: which series of bases specified which amino acids?

Gene
A basic unit of hereditary in living organisms Composed of DNA that code for mRNA and protein Occupies a fix position on chromosome 30,000 base pairs long (out of 3.9 x 10 9 base pairs of DNA)
Image Source: http://www.oncolink.org/library/images/id818-1.gif

Discovery of Gene
In 1866, Gregor Mendel proposed that characteristics of organisms were determined by hereditary elements.
Images Source: http://en.wikimedia.org/

In 1909, Wilhelm Johannsen proposed the term gene to describe Mendel's factors of inheritance.
http://nobelprize.org/nobel_prizes/medicine/laureates/1 933/morgan.jpg

Discovery of Gene
In 1915, Thomas Hunt Morgan found that genes were located on chromosome.

In 1944, Oswald Avery demonstrated that genes were composed of DNA.

Images Source: http://en.wikimedia.org/

Who interpret the genetic code?

The synthesis of proteins; which amino acid arises from a particular nucleotide. His study material required cell-free system: cell walls ruptured and release contents. The material inside cells is called cytoplasm, which can synthesize protein. Strands of template with a known combination of nucleotides RNA were run in the "cell-free" system

The template used is composed of repetive nucleotide The Nobel Prize uracil.

in Physiology or Medicine 1968

Nirenbergs experiment
The protein that emerged consisted only of phenylalanine, one of the 20 kinds of amino acids in proteins. The code is broken! Because the genetic code was known to consist of triplets

http://www.mun.ca/biochem/courses/3107/images/Lodish/Lod4-28.jpg

The experiment showed that UUU is the codon for phenylalanine

Nirenbergs experiment
Testing synthetic RNA in a cell-free system was a key technical innovation. Further experiments revealed codes for most of the known amino acids normally present in proteins.

Genetic code
The genetic code expressed as RNA codons (occur in mRNA ) or DNA codons genetic code is the specific relationship between nucleotide sequence and amino acid sequence consists of 64 triplets of nucleotides which is known as codons Four types of nucleotides in RNA cause 64 possible codons (4x4x4)

Genetic code
With three exceptions, each codon encodes for one of the 20 amino acids used in proteins synthesis Three of these possible codons specify the termination of the polypeptide chain are known as "stop codons" Most of the amino acids are represented by more than one codon The genetic code is degenerate

Genetic code
proteins synthesis is based on the sequence of mRNA DNA transfers information to mRNA in the form of a code defined by a sequence of nucleotides bases During protein synthesis (translation), ribosomes "read" the codon sequence from the 5' end to the 3' end Each amino acid is specified by the mRNA's codon, and then pairs with a sequence of three complementary nucleotides carried by a particular tRNA (anticodon)

Genetic code
Peptide synthesis starts from methionine (Met), coded by AUG The stop codon (UAA, UAG or UGA) signals the end of a peptide Open reading frame (ORF) is the sequence from an initiating codon (ATG) to a stop codon (TAA, TAG or TGA) in a DNA molecule, which is likely to encode a protein

Genetic Code Table

Scientist crack Genetic code of two common cancers

Wellcome Trust Sanger Institute reveal the cancer genome analysis- published on 17 December 2009 Researchers mapped the genetic code for two common cancers: i) lung cancer ii) melanoma Causing deaths of thousands of people per year Lung cancer one million deaths each year

Genetic sequences are from the two men who died from lung cancer and melanoma
For lung cancer, - It has more than 23,000 mutations -One mutation is caused by 15 cigarette smoked -Scientist found that cancer causing agents in tobacco repeatedly attack the DNA

For melanoma, There is a damage of DNA like lung cancer Melanoma contains 30,000 mutations in DNA( 75 % of skin cancer deaths) Caused by ultraviolet light rays

Cancers are caused by the mutations in the DNA of cancer cells

Damage of DNA causes the cells to become abnormal & malfunction Smoking & sunlight is the cause of cancers (lung cancer and melanoma) Sanger Institute used DNA sequencing technologies for these two cancers

I think each step forward is a step toward our goal, our ultimate goal, which is to relieve the suffering from cancer," Dr. Jeanny Argon- Ching said.

video time!! Sit back & relax & enjoy it!!

References
http://www.answers.com/topic/gene http://www.nature.com/scitable/topicpage/Discovery-of-DNAStructure-and-Function-Watson-397 Image source: http://undsci.berkeley.edu/article/dna_checklist