chapter 06

DNA and the expression of genes

DNA is a double helix macromolecule made of nucleotides .
- DNA is made from nucleotide subunits, which is composed of
  - a five-carbon deoxyribose sugar
  - a phosphate group
  - a nitrogen-containing base
  Two chains of nucleotides twist around each other to form a double helix with sugar-phosphate backbones held together by hydrogen bonds between the nitrogen-containing bases.
  The hydrogen bonding between the nitrogen-containing bases occurs in complementary base pairs:
  - Adenine (A) always pairs with Thymine (T).
  - Guanine (G) always pairs with Cytosine (C).
Sequences of nucleotides called genes control cellular functions and make up an individual's genome.
- The full set of genetic material present in an organism is called its genome.
  In eukaryotes, DNA in the nucleus is organized in linear strands called chromosomes.
  Sequences of nucleotides make up genes that code for proteins.
  Humans have 23 pairs of chromosomes, one of each pair inherited from our mother, one from our father, for a total of 46.
  You may inherit different versions of a gene from your parents.
- Since 2000, the genomes of many organisms have been sequenced.
  A human cell has over 3 billion base pairs of DNA, for a total of 6 billion (6 x 10⁹) nucleotides.
  Our genome size is relatively large among organisms, but not the largest.
  Some plants such as onion (Allium species) possess many times as much DNA as a human.
- Alternative versions of a gene that code for different variations of a protein are called alleles.
  You may inherit different alleles from your parents for any given trait, such as hair color.
  Different alleles may result in the production of different proteins and be observed as different traits of an organism, such as petal color.
  An observable trait is called a phenotype, while an individual's alleles make up its genotype (genetic makeup).
  The genotype determines the phenotype.
Much of the human genome are non-coding DNA that are not genes .
- Genes make up only about 2% of human DNA.
  The coding regions of genes provide instructions for synthesizing proteins that can often be observed as phenotypes, e.g. hair color.

Gene expression (exhibiting a phenotype) involves 2 steps:

Gene expression (exhibiting a phenotype)

Messenger RNA (mRNA) molecules are produced by transcription from genes on the DNA. This occurs in the nucleus. Other types of RNA can also be transcribed.	Proteins are produced by translation from the mRNA. This occurs on ribosomes in the cytoplasm.

Transcription involves copying genetic information on DNA to a RNA transcript.
- Transcription
  1. RNA polymerase binds to DNA at a specific region called the promoter site and separates the double helix to single strands.
  2. One of the DNA strands on the gene is used as a template on which RNA nucleotides are built, using the base-pairing rules. Note:
    - Adenine (A) on the DNA pairs with Uracil (U) on the RNA:
    - Adenine (A) always pairs with Uracil (U).
    - Guanine (G) always pairs with Cytosine (C).
  3. The mRNA (or other types of RNA) transcript is released when it reaches the end of the gene.
Translation involves the production of proteins from nucleotide sequences copied onto the RNA transcript.

Translation needs a a "dictionary": the genetic code.
1. A ribosome guides the translation process by binding to mRNA and loading tRNAs.
2. An attachment site on the tRNA binds to three-base codons on the mRNA, using the genetic code (codon table) as a "dictionary" to add amino acids to a protein chain,
3. The protein is released from the complex when the ribosome reads one of three stop codons on the mRNA.

A transfer RNA (tRNA) molecule is single-stranded;
On one end is a three-base attachment site that is complementary to the codon on the mRNA, using base-pairing rules:
- A pairs with U.
- G pairs with C.
The other end carries a specific amino acid.
The match between codon and amino acid is specified in the genetic code.
For example, the codon "ACG" is code for the amino acid "Threonine".

Genetic Code (Codon Table)
A codon is a triplet of 3 nucleotides on the mRNA that codes for an amino acid.
Ribosomes translate each codon to an amino acid; most amino acids are specified by more than one codon.
The codon AUG is both the "start" codon and also a codon for the amino acid Methionine.
There are 3 "stop" codons.

A mutation is a change in the DNA sequence that may affect proteins.
- A mutation is a change in the DNA sequence (gene) of an organism, resulting in an altered protein.
  The mutant fruit fly at the bottom has suffered a mutation in a gene regulating eye shape (phenotype).
  The rate of mutations in cells is about 1 per 10⁸ (hundred million) base pair of nucleotides.
- A mutated DNA sequence is reflected in a changed mRNA codon, leading to a possible change in the amino acid sequence of the translated protein, which may be defective.
  Mutations that change a single base pair are called substitution mutations.
  Insertions and deletions of nucleotides lead to frame-shift mutations that change many amino acids in the protein.
  genetic code
  - What is a substitution mutation in the DNA that causes the illustrated amino acid change from cys (Cysteine) to ser (Serine)?
    - ACA mutated to TCA (or ACG mutated to TCG) hint
- 1. A mutated gene codes for a defective protein, such as the enzyme aldehyde dehydrogenase.
  2. The defective enzyme fails to carry out a chemical reaction.
  3. Molecules fail to be processed and accumulate.
  4. The accumulated chemical acetaldehyde (a byproduct of alcohol breakdown) is toxic, leading to "fast-flushing".
- Insertion mutation
  Use the codon table to follow the insertion of a nucleotide in DNA.
  Insertion of a C in front of the TCG triplet on the DNA yields CTC, all following DNA sequences are shifted over.
  The transcribed mRNA mutated from AGC to GAG.
  The translated protein mutated from ser (Serine) to glu (Glutamate).
- Deletion mutation
  Use the codon table to solve this problem.
  What caused this deletion?
  An incorrect solution:
  the last DNA mutated triplet TCx is wrong, should be CTx.