MUTASI (MUTATION)

The flow of information within a cell involves the transcription of DNA to mRNA and the translation of mRNA to protein?

The flow of information between cell generations involves DNA replication and distribution to two equal daughter cells?

A change in DNA to be replicated and passed on to future generations and to effect protein structure and function if the change occurred in the gene that coded for that protein?

The cause and effect of changes in DNA?

These changes are called mutations

MutationsAny change in the DNA sequence of an organism is a mutation

Mutations are the source of the altered versions of genes that provide the raw material for evolution.

Most mutations have no effect on the organism, especially among the eukaryotes, because a large portion of the DNA is not in genes and thus does not affect the organisms phenotype.

Of the mutations that do affect the phenotype, the most common effect of mutations is lethality, because most genes are necessary for life.

Only a small percentage of mutations causes a visible but non-lethal change in the phenotype.

Mutations

Mutations are RandomA central tenet of biology is that the flow of information from DNA to protein is one way. DNA cannot be altered in a directed way by changing the environment. Only random DNA changes occur.

The simplest mutations are base changes, where one base is converted to another. These can be classified as either: transitions, where one purine is changed to another purine (A -> G, for example), or one pyrimidine is changed to another pyrimidine (T -> C, for example). transversions, where a purine is substituted for a pyrimidine, or a pyrimidine is substituted for a purine. For example, A -> C.

Another simple type of mutation is the gain or loss one or a few bases.

Larger mutations include insertion of whole new sequences, often due to movements of transposable elements in the DNA or to chromosome changes such as inversions or translocations.

Deletions of large segments of DNA also occurs.Types of DNA Change

Types of MutationMutations can be classified according to their effects on the protein (or mRNA) produced by the gene that is mutated.

Point Mutations

Frameshift Mutations

Point MutationsPoint mutations are the most common type of mutation. A single point mutation, also called a base substitution, occurs when a single nucleotide is replaced with a different nucleotide.

A point mutation results in a base pair substitution after replication and possibly a mutant protein after transcription and translation.

There are three types of point mutations: Silent mutation Missence MutationNonsense Mutation

Silent MutationA silent mutation causes no change in the activity of the protein.

A silent mutation is usually the result of a substitution occurring in the third location of the mRNA codon. Third base changes often have no effect on the amino acid sequence of the protein.

The genetic code is degenerate (most amino acids are coded for by several alternative codons), the resulting new codon may still code for the same amino acid.

These mutations affect the DNA but not the protein. They have no effect on the organisms phenotype.

Missence MutationA missence mutation is a nucleotide substitution that changes a codon so that it codes for a different amino acid in the protein. Some missense mutations have very large effects, while others have minimal or no effect. This usually results in a change of the activity of the protein. The change may be harmful or beneficial to the protein. It depends on where the mutation occurs in the proteins structure, and how big a change in the type of amino acid it is.

Nonsense MutationA nonsense mutation is the same as a missense mutation except the resulting codon codes for a STOP signal.

The result is a premature termination of translation.

The protein is shorter than usual and does not contain all the amino acids that it should. Therefore, this protein is most likely nonfunctional.

Frameshift MutationsAnother type of mutation is a frameshift mutation which is caused by the insertion or a deletion of a base pair.

An inserted or deleted nucleotide alters the triplet grouping of nucleotides into codons and shifts the reading frame so that all nucleotides downstream from the mutation will be improperly grouped.

The result is a protein with extensive missense ending sooner or later in nonsense.

What causes mutations?A mutation can be the result of different events. Errors made during replication, repair, or recombination can all lead to point or frameshift mutations. Mutations resulting from such errors are spontaneous mutations.

DNA replication is very accurate, but DNA polymerase is not 100% accurate. Mutations that are not due to external factors are called spontaneous mutations.

Our body temperature (37oC) increases the rate of spontaneous mutation. The base C spontaneously converts to the base U readily at high temperatures.

A CG base pair can become a UG base pair. If the mismatch is not detected and repaired before DNA replication begins, the U will be paired with an A during replication. The UG will thus become an UA and a CG base pair. Replacement of the U or further replication will result in the UA becoming an TA base pair. So, heat causes CG base pairs to become TA base pairs.What causes mutations?

Environmental factors also influence the rate of mutation

A mutation can also result from the action of physical and chemical agents known as mutagens. We will now explore three mutagens: nitrous acid, base analogs, and UV light.

Nitrous Acid (HNO2)Nitrous acid affects DNA complementation.

The acid randomly modifies the base adenine so that it will pair with cytosine instead of thymine. HNO2 causes GC base pairs to become AT base pairs, and AT base pairs to become GC base pairs

This change is made evident during DNA replication when a new base pair appears in daughter cells in a later generation.

The salt of nitrous acid (nitrite) can be found in preserved meats and is mutagenic.

Nitrous acid (HNO2)

Base AnalogA base analog is a compound sufficiently similar to one of the four DNA bases but have different pairing properties.

For example, 5-bromouracil is the analog of thymine but sometimes pairs with guanine and 2-aminopurine is the analog of adanine but sometimes pairs with cytosine. It can be incorporated into DNA and pair with A or G. It results in AT to GC changes or GC to AT changes

The incorporation of a base analog will to a base pair substitution in that appears in daughter cells in a later generation.

5-Bromouracil

X-rays & UV LightIonizing radiation (X-rays) & nuclear radiation cause mutations by creating highly reactive free radicals can cause minor or major mutations. They can react with DNA and cause breaks in the DNA backbone. This may destroy individual genes, or result in loss of whole sets of genes through loss of pieces of chromosomes.

UV rays from sunlight result in the formation of TT dimers

UV Light

UV LightExposure to direct UV light induces covalent linking between adjacent thymine nucleotides on a DNA strand forming a thymine dimer.

These dimers cause the strand to buckle, disrupting normal base pairing. This prevents proper replication and transcription.

Bacteria have enzymes to fix the damage created by UV light.

An enzyme cuts the DNA at two point and removes the damaged portion.

UV LightT-T dimers can be repaired, but if they remain unrepaired until replication, the opposite strand will be replicated incorrectly. DNA polymerase will skip the bases included in the dimer, and a 2 nucleotides will be lost from the DNA.

DNA polymerase synthesizes a new DNA segment using the healthly strand as a template.

DNA ligase joins the new fragment to the old strand.

Mutation RateMutations are random events and there is no way of knowing when a mutation will occur. Genes do, however mutate spontaneously at a characteristic rate, making it possible to assign probabilities to certain mutation events. The probability that a gene will mutate when a cell divides is called the mutation rate.

Mutation RateSpontanoeus mutation rate for the average gene is 0.000000001. This means a mutation event is estimated to occur once in every million genes replicated.

The presence of a mutagen increases the rate of mutation to 0.00001 to 0.001. This means that a mutation event is estimated to occur once in every hundred thousand to one hundred thousand genes in the presence of a mutagen.

Sickle-cell anemiaSickle-cell anemia is due to a recessive gene. Homozygotes for the sickle-cell allele have sickle-cell anemia. They have problems delivering oxygen to their tissues when they are stressed and oxygen levels in their blood start to drop.

The gene codes for Hb, one of the two proteins that make up the hemoglobin 2 molecule.

A single base-pair change in DNA can account for the amino acid change

HbS, sickle cell hemoglobin, is a change in the beta-globin gene, where a GAG codon is converted to GUG. GAG codes for glutamic acid, which is a hydrophilic amino acid that carries a -1 charge, and GUG codes for valine, a hydrophobic amino acid. This amino acid is on the surface of the globin molecule, exposed to water. Under low oxygen conditions, valines affinity for hydrophobic environments causes the hemoglobin to crystallize out of solution.

-Hb has an amino acid sequence containing 146 amino acids.In normal -Hb, the sixth amino acid is GLUIn sickle-cell -Hb, the sixth amino acid is VALin mRNA:GLU is coded by either GAA or GAGVAL is coded by GU_

NormalSickle cell anemiaTemplate:... CTT ...... CAT ...Coding:... GAA ...... GTA ...

Codon:... GAA ...... GUA ...

Amino acid:... GLUTAMIC ACID ...... VALIN ...