From DNA to Proteins

Nucleic Acids
Nucleic acids are a type of macromolecule made from repeating units called nucleotides. Each nucleotide is made of the same basic parts:
A sugar. A base that contains nitrogen. A phosphate (PO4) ion.

DNA and RNA

Each molecule has the same basic structure, except the 5-carbon sugar.
Ribose in RNA. Deoxyribose in DNA.

RNA is also usually single-stranded.

Nitrogenous Bases
There are five different types of nitrogenous bases that make up DNA and RNA.
DNA: Thymine (T), Adenine (A), Cytosine (C), and Guanine (G) RNA: Uracil (U) instead of Thymine (T).

The sequence of these bases codes for all of the proteins produced by the body.

DNA
When a cell needs to produce a new protein, only one specific piece of DNA from one chromosome is involved. The human genome has 23 pairs of chromosomes.

Insulin
A total of 110 amino acids, coded by 330 base pairs, builds insulin. The gene for insulin is located on chromosome 11. The DNA of chromosome 11 contains about 134 million base pairs.
0.00025% of this chromosome codes for insulin.

Transcription
Takes place in the nucleus. A messenger RNA molecule (mRNA) is copied from DNA by unzipping a portion of the DNA helix that corresponds to a gene One side of the DNA strand is transcribed into the appropriate sequence of A, U, C, & G.

Transcription

The Genetic Code

Base pairs are translated in sets of three, called codons. Codons are like the words of the DNA language. One codon corresponds to one amino acid (the building blocks of proteins).
Examples:
UUU = phenylalanine GGA = glycine AAA = lycine

Cracking the Code

The genetic code is redundant but not ambiguous;
Not ambiguous meaning that each codon specifies only one amino acid.
Example: UUU always codes for phenylalanine.

Redundant meaning that more than one codon may signals a specific amino acid.
Example: Serine is coded by UCA, UCG, UCC, and UCU.

Codon chart

Translation
Takes place in the cytoplasm (ribosomes in the rough E.R.) Ribosomes read the codons of the mRNA and instruct tRNAs (with matching anticodons) to bring in specific amino acids to be added to the growing polypeptide chain (protein).

LE 17-4
Gene 2 DNA molecule Gene 1

Gene 3

DNA strand (template)

TRANSCRIPTION

mRNA

5 Codon

TRANSLATION

Protein

Amino acid

Insulin
The hormone insulin is made of two protein chains, a connecting peptide, and a signal peptide.
Signal peptides tell the endoplasmic reticulum to direct the protein outside of the cell. Connecting peptides keep the two chains inactive until the insulin is actually needed.

How Insulin is Built

1. The double helix of the relevant section of chromosome 11 is unzipped. 2. The mRNA molecule is transcribed using one of the DNA strands as a template. 3. The mRNA molecule is sent outside the nucleus to the rough endoplasmic reticulum.

How Insulin is Built

4. The mRNA is received by a ribosome in the rough E.R. 5. The ribosome starts translating the mRNA codons into amino acids. 6. The protein is built, one amino acid at a time, using tRNA molecules.

How Insulin is Built

The first 24 amino acids are a signal peptide, telling the endoplasmic reticulum not to release the hormone directly into the cytoplasm. The next 30 amino acids make the first part of the insulin protein. The following 31 amino acids make a connecting peptide. This keeps the two parts of insulin separate until it is ready to be activated. The last 21 amino acids form the second part of the insulin protein.

How Insulin is Built

The insulin is sent to the Golgi, where it is packaged. The insulin will be released by the pancreas when blood glucose levels are too high.

Evolution of the Genetic Code

The genetic code is nearly universal, shared by the simplest bacteria to the most complex animals Genes can be transcribed and translated after being transplanted from one species to another. Most medicinal insulin produced now comes from cultures of bacteria.

Mutations
Mutations are changes in the genetic material of a cell or virus Point mutations are chemical changes in just one base pair of a gene.
This may change a single amino acid in the protein sequence, which could alter the entire shape of the protein.

LE 17-23

Wild-type hemoglobin DNA

3 5 3

Mutant hemoglobin DNA

5

mRNA

mRNA

Normal hemoglobin

Sickle-cell hemoglobin

Types of Point Mutations

Point mutations within a gene can be divided into two general categories
Base-pair substitutions Base-pair insertions or deletions

Substitutions
A base-pair substitution replaces one nucleotide and its partner with another pair of nucleotides

Insertions and Deletions

Insertions and deletions are additions or losses of nucleotide pairs in a gene These mutations have a disastrous effect on the resulting protein more often than substitutions do Insertion or deletion of nucleotides may alter the reading frame, producing a frameshift mutation

LE 17-25
Wild type mRNA 5 Protein Amino end Base-pair insertion or deletion Frameshift causing immediate nonsense Extra U

3 Stop Carboxyl end

Stop Frameshift causing extensive missense Missing

Insertion or deletion of 3 nucleotides: no frameshift but extra or missing amino acid Missing

Stop

Mutagens
Spontaneous mutations can occur during DNA replication, recombination, or repair Mutagens are physical or chemical agents that can cause mutations.
Examples include nuclear radiation, UV light, Xrays, chemicals in tobacco smoke.