Gene mutation

Mutations                                                                                                            substitutions of bases has three oucomes:

A nonsense mutation- occures if a stop codon is formed. The production on the polypeptide is stopped so the final protein would most likely be significantly different and form a non-funtioning protein.

A mis-sense mutation- when a different amino acid is coded for. The polypeptide produced will differ by one amino acid. The effect of this difference depends on the role of the original amino acid. 

A silent mutation- when the substituted base still codes for the same amino acid. This is due to the degerate nature of the genetic code.                                          

Deletion of bases:

Occurs when a base is delelted causing a frame shift, where the nucleotides move along to replace the missing base, creating new amino acids. 

Deletion at the end of the chain would have a lesser effect than a deletion at the start

Causes of mutations:

can occur spontaneously during DNA replication. spontaneous mutations are permanent changes in DNA that occur without any outside influence.

There are 1 or 2 mutations per 100,000 genes per generation.

outside factors that increase mutations rates are known as mutagenic aents or mutagens. 

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

Mutations create genetic diversity necessary for for natural selection 

They also produce organisms that are less well suited to its environment 

mutations that occur in body cells rather than gametes can disrupt normal callular activities, such as cell division

genetic control of cell division:

most cells divide at a constant rate to ensure that dead or worn out cells are replaced. 

In normal cells this rate is tightly controlled by two genes:

proto-oncogenes- stimulate cell division

tumour suppressor genes- that slow cell division 

Role Of Proto-Oncogenes

stimulate cell division 

in a normal cell, growth factors attch to a receptor protein on the cell surface membrane and switch on genes for DNA replication via relay proteins in the cytoplasm. 

A gene mutation can cause proto-oncogenes to mutate into oncogenes.

This effects cell division in two ways:

The receptor protein on the cell-surface membrane can be permenantly activated, so that cell division is switched on without growth factors 

The oncogene may code for a growth factor that is then produced in excessive amounts, stimulating excessive cell division 

The result is that the cells divide too rapidly and a tumour or cancer develops

Role Of Tumour Suppressor Genes

Inhibit cell division 

A normal tumour suppressor gene will maintain normal rates of cell division and prevent the formation of tumours 

If a tumour suppressor gene mutates it becomes inactivated

The mutant cells formed are usually structurally and functionally different from normal cells

Most mutated cells die 

Those that survive are capable of making clones of themselves and forming tumours 

Not all tumours are harmful (Malignant) some are harmless (Benign)

All cells contain the same genes so are capable of making everything the body can produce

Only certain genes are expressed in all cells.

some genes are permenantly switched on others are switched on and off when needed.

Differentated cells- produce different proteins. The proteins a cell produces ared coded for by the genes it possesses that are switched on

Fertilised egg cells can create all types of cells and mature into any body cell-  totipotent

During cell specialisation only some genes are expressed, as only part of the DNA is translated into proteins 

The ways in which genes are prevented from expressing themselves are:

Preventing transcription so preventing the production on mRNA

Breaking down mRNA before its genetic code can be translated

stem cells are undifferentiated divided cells that occur in adult animal tissues and need to be constantly replaced. 

They are found in the inner lining of the small intestine, the skin and the bone marrow, which produces red and white blood cells

Under certain conditions stem cells can develop into any other type of cell

Stem cells also occur at the earliest stage of the embryo development- called embryonic stem cells

Once cells have matured and specialised they can no longer develop into other cells- They lose thier totipotency

Only a few totipotent cells exist in mature animal- called adult stem cells 

Mature plants have many totipotent cells

Growing cells outside of a living oranism- called in vitro development 

For transcription to begin the gene needs to be stimulted by specific molecules that move from the cytoplasm into the nulceus- called transcrptional factors

Each transcriptional factor has a site that binds to a specific region of the DNA in the nulceus 

When it binds it stimulates this region of DNA to begin the process of transcription

Messenger RNA is produced and the genetic code it carries is then translated into a polypeptide 

When a gene is not being expressed, the site on the transcriptional factor that binds to DNA is blocked by an inhibitor molecule

This inhibitor molecule prevents the transcriptional factor binding to DNA ans so prevents transcription and polypeptide synthesis  

Oestrogen is lipid soluble so diffuses easily through the phospholipid portion of cell-surface membranes

Once inside the cytoplasm of a cell oestrogen combines with a site on a receptor molecule of the transcriptional factor. The shape of this site and the shape of the oestrogen are complementary

By combining with the site, the oestrogen changes the shape of the receptor molecule. This change of shape releases the inhibitor molecule from the DNA binding site on the transcriptional factor

The transcriptional factor can now enter the nucleus through a nuclear pore and combine with DNA 

The combination of the transcriptional factor with DNA stimulates trancription of the gene that makes up the portion of DNA

Gene expression can be prevented by breaking down messenger RNA before its genetic code can be translated into a polypeptide

Small intrfering RNA (siRNA)- are small double- stranded sections of RNA - are essentail to this process 

The process occures as follows:

An enzyme cuts large double-stranded molecules of RNA into smaller sections (siRNA)

One of two siRNA stands combines with an enzyme 

The siRNA molecule guides the enzyme to a mRNA molecule by pairing up its bases with the complementary sections of the mRNA molecule

Once in position the enzyme cuts the mRNA into smaller sections 

The mRNA is no longer capable of being translated into a polypeptide 

This means that gene has not been expressed- it has been blocked

siRNA could be used to identify the role of gene in a biological pathway. Some siRNA that blocks a particular gene could be added to cells. By observing the effects we could determine what the role of the blocked gene is.

As some diseases are caused by genes, it may be possible to use siRNA to block these gene and so prevent the disease.