Genetics - DNA Structure and Function

What is the timeline of genetic discoveries?

• Friedrich Miescher - 1868

• Avery, MacLeod and MacCarthy - 1944

• Alfred Hershey and Martha Chase - 1953

• Rosalind Franklin - 1953

• Watson and Crick - 1953

What was Miescher’s discovery?

• Isolated ‘nuclein’ from human pus

• Later renamed nucleic acid

• Molecule had a high molecular weight, was acidic and contained lots of phosphorous

• Obtained from other animal tissues and yeast cells

What was Avery, MacLeod and McCarthy’s discovery?

• Completed transformation experiments

• Used disease causing S-strain and harmless R-strain

• Prepared an extract of different samples and implemented them into the R-strain

• Only the DNA caused the R-strain to become disease causing

• Part of the first evidence that DNA carries heritable information

What was Hershey and Chase’s discovery?

• Used bacteriophages which contain only DNA and protein

• Labelled DNA with 32P

• Labelled protein with 35P

• Only 32P was present in infected bacterial cells and passed to bacteriophage progeny

What was Franklin’s discovery?

• Used X-Ray crystallography to identify a double helix structure of DNA

• Proposed that phosphate molecules are located on the outside of the helix

What are the two most valuable properties of DNA?

• Stability over time

• Faithful replication

Why is DNA stability an important property?

Two strands means that mutations are less harmful as there are two strands to be affected

Why is faithful replication of DNA an important property?

Semi-conservative replication means one strand is parent DNA and the other is sister DNA

How can chromosomes and genes be viewed?

Using probes with fluorescent colours (DNA paint)

What is the physical structure of DNA?

• Right handed double helix

• Contains major and minor grooves due to hydrogen bonding between the bonded base pairs

What is the chemical structure of DNA?

• Polymer made of nucleotides

• Nucleotides are composed of a pentose sugar, phosphate group and a nitrogen-containing organic base

• Four possible bases in DNA (A, T, C, G)

• DNA strands are antiparallel and have directionality (5’ and 3’ ends)

• DNA helix is made of two polynucleotide strands held by hydrogen bonds between complementary paired bases

What are the two categories of bases?

• Pyrimidine base

• Purine base

• Cytosine, Thymine and Uracil are pyrimidine bases

• Adenine and Guanine are purine bases

• Purine base will always bond with a pyrimidine base

How can the strands of DNA be separated?

Heated to break the hydrogen bonds between strands

Why are major and minor grooves important in DNA?

DNA binding proteins need to be a specific shape to fit the major and minor grooves

What is the genome?

All the DNA in the nucleus of a cell or organelle

How is the genome organised?

• Distributed among discrete units called chromosomes

• Can be viewed as a karyotype

How is DNA organised within a cell?

• Total DNA length for one cell is 2 metres long

• Nucleus is 10 micrometres

• DNA is wrapped around proteins to condense it

• DNA wraps around 8 core histones twice to form nucleosomes

• 2x H2A

• 2x H2B

• 2x H3

• 2x H4

• H1 brings the nucleosomes together to form a chromatin fibre

• Chromatin is further condensed by scaffold proteins

What are the two types of chromatin?

• Euchromatin - less compact DNA, contains DNA that is commonly transcribed

• Heterochromatin - more compact DNA, contains DNA that is not commonly transcribed