Goals of this section:

1) Describe the structure of DNA and RNA

2) Name 4 similarities and 6 differences between DNA and RNA

3) Describe the process of DNA replication and discuss its significance

4) Describe the process of transcription and translation as component parts of protein synthesis, naming each participant and giving its function

5). Describe how mutations arise

6). Describe the link between DNA repair and cancer

One of the major goals of modern biological science is to understand how to get from:

genes -->?-->?--->? --->?----> traits

Understanding the only partially known steps indicated by ? is important not only from the standpoint of basic knowledge but also for understanding, treating and ultimately curing almost every human medical problem

Requires understanding chemical makeup of genes

Genetic material in all organisms except for some viruses is DNA

DNA is a double helix of 2 single stranded polymers would around each other in a specific way

Each polymer is made up of a subunits called nucleotides

A

G

C

T

Bases:

A (Adenine)

G (Guanine)

C (Cytosine)

T (Thymine)

Identity of base determines identity of nucleotide

Bases on the inside of the double helix hold the two strands together by specific chemical bonds

Complementary base pairs

A & T G & C

Even with only four bases, essentially infinite number of possible sequences

Sequences of 100 >>100,000 may constitute individual genes

In one set of 23 human chromosomes (1 of each pair) there are 3 x 10⁹ base pairs

=> 1.3 x 10⁸ base pairs/chromosome(avg.), range 5x 10⁷ to 5 x 10⁸

Each chromosome contains a single double helical strand of DNA of this length

On average only 10% of the overall DNA sequence contains functional genes, the rest has an unknown function

Because of complementary base pairing, if the base sequence of one strand of the two is known, the sequence of the second is also known

Strand 1: ATGCCGAAT

Strand 2:TACGGCTTA

Part of the cell machinery uses this principle to replicate DNA

Thus question of how genes determine traits can become

how information encoded in DNA determines the structure and function of macromolecules

Proteins are polymers composed of the 20 amino acids

Form the major structural elements and enzymatic machinery of cells

One class of RNA called messenger RNA (mRNA) has its base sequence "translated" into a sequence of amino acids

Information in the mRNA is read in groups of three bases

Each of the 64 possible 3 base sequences ("codons") has a meaning, either one of the 20 amino acids or as the "stop" codon to stop translation

The genetic code shows redundancy i.e. more than one three base sequence may specify a particular amino acid

E.g.

Amino acid sequence determines the three dimensional structure of the protein

Structure determines it s function

Function determines a trait

Ribosomes hold and orient messenger RNA in such a way so that tRNA’s can bind

Each tRNA carries a particular amino acid

tRNA’s recognize a particular codon of the mRNA by means of their complementary "anticodon"

While attached to the ribosome, adjacent amino acids can form a peptide bond

Base sequence in the DNA by means of transcription and translation results in a unique amino acid sequence.

Each unique amino acid sequence results in a unique three dimensional shape and function for the protein

Mutations are changes in DNA base sequence which are permanent and can be inherited

DNA --> RNA --> mRNA --> protein sequence -->

3D protein structure --> function ---> trait

Change DNA -->change RNA --> change mRNA --> change protein sequence --> change 3D protein structure

--> change function ---> change trait

Changes in traits may be considered beneficial to an organism. In this case it gives the organism a selective advantage and will come, in the process of evolution, to predominate in members of a species.

genetic diseases (mild - fatal)

over 600 known and mapped onto chromosomes,

100’s more known but not mapped

muscular dystrophy

cystic fibrosis

sickel cell

cancers

birth defects (?)

Many mutations due to effects of mutagenic chemicals and radiation

Mutagenic chemicals include free radicals and nitrosamines, compounds in smoked and char-broiled foods

Radiation includes ultraviolet ( UV ) and "ionizing"

Ionizing includes x-rays., cosmic rays, radiaoctive decay in surroundings

DNA breaks and alterations occur all the time

Cells have the ability to repair DNA

It is difficult to determine the amount of damage a particular mutagenic agent might have.

Might expect that low doses of exposure to e.g. radiation could be handled by DNA repair

Large doses in a short time might temporarily overwhelm the repair systems

This has importance for public health measures since most animal studies are done at higher levels of mutagenic agents than typical exposure levels. This is in order to get a measurable effect in a limited number of test animals.

If for instance, a particular level of mutagen produces 1 problem in 10,000 animals, you would need to use 40-50,000 animals to get statistically significant results.

In order to do an experiment with 100 animals researchers use doses 500x higher and hope that the effect scales linearly.

Some evidence that a "threshold model" is more realistic.

Recent evidence closely links deficiencies in DNA repair with certain types (maybe many or most types) of cancer

DNA repair enzymes (proteins) are encoded by genes

DNA repair is a trait just like any other trait

Some people inherit mutant alleles of one of more of these genes so that they are deficient for DNA repair (i.e. the pheotype they express is "deficiency in DNA repair")

This repair deficiency apparantly leads to lowered ability to repair DNA damage (mutations) in all genes and this leads to cancer.

This will be manifested as a tendency to "inherit" certain kinds of cancer