DNA: The biomolecule of heredity

Genetics timeline
1882 Walter Fleming discovers rod-shaped bodies he calls "chromosomes

1902 Walter Sutton proposes that hereditary factors must lie on chromosomes. 1915 Thomas Hunt Morgan shows that genes are lined up along chromosomes.

Genotype: encoded in chromosomes

Chromosome - a long strand of DNA, packaged together with proteins and other molecules

Organism Tomato

Mouse Human Dog

Number of Chromosome Pairs 12 Pairs 20 Pairs 23 Pairs 39 Pairs

What are chromosomes made of?

Chromosomes are made up of DNA and proteins A gene encodes information for the synthesis of a protein

Amino acids and proteins

Proteins = polymers of amino acids

20 amino acids are commonly found in proteins Each amino acid has a similar, yet unique structure

DNA and proteins

DNA composed of four repeating nucleotides units : A, G, C and T Each nucleotide contains a sugar, a phosphate and a nitrogen base DNA initially considered too simple, regular to contribute to genetic variation Proteins widely considered as probable hereditary substance

DNA is the genetic material

"S" or SMOOTH coat strain: lethal to mice

"R" or rough strain; non-lethal

heat-killed S: mouse lives

mixture of the heat-killed S and R strain mouse dies

Avery's results were either ignored or attributed to trace contamination of his DNA fractions with protein

1952 Martha Chase and Alfred Hershey prove that DNA is the substance that transmits inherited traits from one generation to the next. Hershey receives a Nobel Prize in 1969 for this work.

Chargaffs Rules

Erwin Chargaff documented that that in all species, [ A ] = [ T ] and [ C ] = [ G ]

Elucidating DNA structure

1953 James Watson and Francis Crick determine that the structure of the DNA molecule is a double helix They elucidate DNA structure using X-ray crystallography images

DNA structure
DNA = long polymer of nucleotides backbone made of sugars and phosphate groups joined by ester bonds Sequence of bases along the backbone encodes genetic information

The four DNA bases

Complementary base pairs in the DNA double helix

Figure 4-3 Molecular Biology of the Cell ( Garland Science 2008)

Figure 4-5 Molecular Biology of the Cell ( Garland Science 2008)

B DNA
Antiparallel, right-handed double helix. Bps to the axis of the helix Axis passes through center of bps Each bp rotated by 36 from adjacent base pair Bps are stacked 0.34 nm apart from one another. pitch = 3.4 nm has MAJOR and MINOR groove

Other DNA forms

A form
Right-handed Found in a solution with higher salt concentrations or with alcohol added

Z form
Left-handed So-called because its bases seem to zigzag Found in DNA molecules with alternating G-C sequences in alcohol or high salt solution

Form A B Z

Residues Pitch per turn 24.6 33.2 45.6 ~11 ~10 12

Inclination of base pair from horizontal +19 -1.2 -9

Parameters
Direction of helical rotation Residues per turn of helix

A Form
Right 11 33

B Form
Right 10 36

Z-Form
Left 12 base pairs -30

Rotation of helix per residue (in degrees)

Base tilt relative to helix axis (in degrees) Major groove Minor groove

20 narrow and deep wide and shallow Anti

6 wide and deep narrow and deep Anti

7 Flat narrow and deep

Orientation of Nglycosidic Bond

Anti for Py, Syn for Pu

occurs in stretches of alternating purinepyrimidine base pairs

Comments

most prevalent within cells

Semi conservative replication

Figure 4-8 Molecular Biology of the Cell ( Garland Science 2008)

Meselsohn and Stahl experiment

Bacteria grown in 15N After a few generations, bacteria transferred to normal medium (14N). DNA density analyzed by isopycnic centrifugation DNA density shifted from heavy to light via an intermediate half-way between heavy and light DNAs

Gene Expression
The genes in a genome do not have any effect on cellular functions until they are "expressed Different types of cells express different sets of genes, thereby exhibiting various shapes and functions

"Gene expression" = production of a protein from its gene

Figure 4-6 Molecular Biology of the Cell ( Garland Science 2008)

The flow of genetic Information

Figure 6-2 Molecular Biology of the Cell ( Garland Science 2008)

Transcription

The genetic code

Translation

The flow of genetic information

The human genome

Genome sizes are highly variable

"C-value paradox"
the apparent discrepancy between the complexity of the organism and the length of its DNA (genome)

RNA structure and function

Types of RNA
mRNAs messenger RNAs code for proteins ribosomal RNAs form basic structure of ribosome catalyze protein synthesis transfer RNAs adaptors between mRNA and amino acids

rRNAs

tRNAs

Types of RNA
snRNAs small nuclear RNAs Involved in splicing of pre-mRNA small nucleolar RNAs used to process and chemically modify rRNAs function in diverse cellular processes, e.g., 1. telomere synthesis 2. X-chromosome inactivation 3. transport of proteins into the ER

snoRNAs

Other noncoding RNAs

Figure 6-4a Molecular Biology of the Cell ( Garland Science 2008)

Figure 6-4b Molecular Biology of the Cell ( Garland Science 2008)

Backbones of DNA and RNA formed by 3-to-5 phosphodiester linkages

DNA and RNA structure

Common elements of RNA secondary structure

A tRNA molecule

Two-dimensional map of the secondary structure of 16S rRNA from bacteria, showing the location of base-paired stems and loops