Genetic Control

In eukaryotic cells, DNA is confined to the nucleus; however synthesis of proteins takes place in the cytoplasm. So to transfer DNA to the cytoplasm to be translated into proteins, DNA codes are transcribed onto a single-stranded molecule called ribonucleic acid (RNA).

Messenger RNA is is the type of RNA that transfers the DNA code from the nucleus to the cytoplasm; it is small enough to leave through nuclear pores. The mRNA code is used to determine the sequence of amino acids in the proteins which are synthesised there. It is this sequence of nucleotide bases that is called the genetic code. 

mRNA is complementary to DNA. 

Features of the genetic code:

• each amino acid is coded for by three nucleotide bases (codon)
• degenerate code: most amino acids have more than one codon
• 3 stop codons: that don't code for any amino acid. They mark the end of a polypeptide chain
• non-overlapping: each base in the sequence is read only once
• universal: same codon codes for the same amino acid in all organisms

RNA is a polymer made up of repeating mononucleotide sub-units. It forms a single strand.

• the pentose sugar ribose
• one of the organic bases: adenine (A), guanine (G), cytosine (C), uracil (U)
• phosphate group

Messenger RNA:

• long strand that is arranged in a single helix
• when formed, mRNA leaves the nucleus via nuclear pores and enters the cytoplasm, where is associates with ribosomes
• it acts as a template which proteins are built upon as it has the correct sequences of many triplets of organic bases that code for specific polypeptides
• easily broken down and therefore exists only when it is needed

Transfer RNA:

• relatively small molecule
• single stranded chain folded into a clover-leaf shape, with one end of the chain extending further than the other- this is where amino acids easily attatch
• several types, each able to carry a single amino acid
• at the opposite end of tRNA, there is a sequence of three bases (anticodon)
• for each amino acid there is a different sequence of bases on the anticodon

On RNA, thymine is replaced with uracil. RNA can bind with both DNA and other RNA.

DNA provides the instructions in the form of a long sequence of nucleotides. A complementary section of part of this sequence is made in the form of pre-mRNA: transcription. The pre-mRNA is spliced to form mRNA. This mRNA is used as a templateto which complementary tRNA molecules attatch and the amino acids are linked to form a polypeptide: translation. 

Transcription is the process of making pre-mRNA using part of the DNA as a template

• DNA helicase breaks the hydrogen bonds between the bases on a specific region of the DNA molecule, causing the two strands to separate and expose the bases in that region
• RNA polymerase moves along one of the DNA strands, known as the template strand, causing the nucleotides on this strand to join with complementary ones from the pool presented in the nucleus
• E,g guanine on DNA links to cytosine base of a free nucleotide
• As the RNA polymera adds the nucleotides one at a time, the DNA strand rejoins behind it, therefore only around 12 base pairs are exposed at any one time
• when RNA polymerase reaches the stop code, it detatches and the production of mRNA is complete

Dna is made up of sections called exons that cose for proteins and sections called introns that do not code for proteins. These non-functional introns are removed and the functional exons are joined together during splicing. 

• DNA provides instructions in the form of a long sequence of nucleotides
• a complementary section of part of this sequence is made as pre-mRNA during transcription
• the pre-mRNA is modified to mRNA by removing the base sequences copied from non-functional DNA, introns, during splicing
• the mRNA is used as a template for complementary tRNA molecules attatch and the amino acids they carry are linked to form a polypeptide, during translation

Once mRNA has passed out of the nuclear pore, it determines the synthesis of a polypeptide

• a ribosome becomes attatched to the starting codon at one end of the mRNA molecule
• the tRNA molecule with the complementary anticodon sequence moves to the ribosome  and pairs up with the sequence on the mRNA. This tRNA carries an amino acid.
• a tRNA molecule with a complementary anticodon pairs with the next codon on the mRNA. This tRNA molecule carries another amino acid
• the ribosome moves along the mRNA, bringing together two tRNA molecules at any one time, each pairing up with the corresponding two codons on mRNA
• an enzyme and ATP join the two amino acids on the tRNA by a peptide bond
• the ribosome moves on to the third codon in the sequence on the mRNA, by linking the amino acids on the second and third tRNA molecules
• as this happens, the first tRNA is released from the amino acid and is free to collect another amino acid from the amino acid pool in the cell
• this process continues until a complete polypeptide chain is built up
• the synthesis of a polypeptide continues until a ribosome reaches a stop codon. At this point, the ribosome, mRNA and last tRNA molecule all separate and the polypeptide chain is complete

The DNA triplets that make up a gene determine the codons on mRNA. The codons on mRNA determine the order in which the tRNA molecules line up. This order determines the sequence of amino acids in the polypeptide. So genes precisely determine which proteins a cell manufactures.

Mutation: a change to the sequence of bases in DNA

Substitution:

This is where a nucleotide in a DNA molecule is replaced by another nucleotide that has a different base. It could result in:

• a nonsense mutation: base change results in the formation of one of the three stop codons that mark the end of a polypeptide chain. As a result, polypeptide production would be stopped prematurely, the final protein could not perform its normal function
• a mis-sense mutation: the base change results in a different amino acid being coded for
• a silent mutation: when the substituted base still codes for the same amino acid as before. This is due to the degenerate nature of the genetic code.

Deletion:

When a nucleotide is lost from the normal DNA sequence. The loss of a single nucleotide can change the entire amino acid sequence of the polypeptide. One deletion of a nucleotide causes a 'frame-shift' as the reading frame has shiften to the left by one letter.

Gene mutations can arise spontaneously during DNA replication. Spontaneous mutations are permanent changes in DNA that occur without any outside influence. The besic mutation rate is increased by outside factors, known as mutagenic agents. For example:

• high-energy radiation that can disrupt the DNA molecule
• chemicals that alter the DNA structure or interfere with transcription

Mutations produce the genetic diversity necessary for natural selection and speciation. However they often produce an organism that isn't well suited to the environment. Mutations that occur in body cells rather than in gametes can disrupt normal cellular activities, such as cell division.

Proto-oncogenes that stimulate cell division

Growth factors attatch to a receptor protein on the cell surface membrane and, via relay proteins in the cytoplasm, 'switch on' the genes necessary for DNA replication. A gene mutation can cause proto-oncogenes to mutate into oncogenes. These oncogenes can affect cell division in two ways, resulting in too much cell division (tumour/cancer develops).

• the receptor protein on the cell-surface membrane can be permanently activated, so that cell division is switched on even in the absense of growth factors
• these oncogenes can code for a growth factor that is produced in excessive amounts, stimulating excessive cell division

Tumour Suppressor Genes that slow cell division

These maintain normal rates of cell division and prevent the formation of tumours. If a tumour suppressor gene becomes mutated, it is inactivated so stops inhibiting cell division, which therefore increases. The mutant cells formed are structurally and functionally different. Most die, but those that survive are capable of making clones of themselves and forming tumours.