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School Biology Notes: Genetic variation - causes and consequences of mutations

An introduction to genetic variation, the causes and formation of mutations and consequences

 Doc Brown's school biology revision notes: GCSE biology, IGCSE  biology, O level biology,  ~US grades 8, 9 and 10 school science courses or equivalent for ~14-16 year old students of biology

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(a) Introduction to genetic variation

(b) Changes can happen to the DNA of the genome - mutations & variants

(c) What causes mutations?

(d) Types of mutation

(e) What are the consequences of mutations?

(f) Extra notes on non-coding DNA



(a) Introduction to genetic variation

This page will help you understand that ...

Genetic variants are caused by alterations in the common nucleotide sequences in the DNA of genes.

The term variant can be used to describe an alteration that may be benign (harmless), pathogenic (harmful), or of unknown significance.

The term variant is increasingly being used in place of the term mutation.

Variants are key to successful evolution because genotype changes (usually of the smaller type) can lead to changes in phenotype.

Human genetic variation is the genetic differences both within and among populations.

There may be multiple variants of any given gene in the human population, that is two different alleles.

The different alleles, different versions of a same gene, can lead to difference in phenotypes - the characteristics an organism displays.

A mutation may defined as any change in a DNA compared to normal that results in a rare and abnormal variant.

See the evolution page for lots more notes on variation - genetic and environmental


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(b) Changes can happen to the DNA of the genome - mutations & variants

Sometimes DNA may mutate, meaning a random change occurs in a DNA sequence of an organism.

It is possible for the mutation to be inherited.

This automatically changes the sequence of bases in the DNA molecule.

Therefore the gene expression may be altered or inhibited.

Here we are dealing with a different version of the gene - a genetic variant (also called an allele).

Any mutation changes the sequence of bases in a strand of DNA which produces a different form of the gene (allele), and is called a genetic variant.

In the course of evolution advantageous mutations are more likely to be inherited through successive generations.

All the different versions of genes are called genetic variants or alleles and are formed by mutations (but do not assume they are all harmful to the functioning of an organism!).

diagram of chromosome genes with normal pair of alleles defective alleles gcse biology igcse

Despite the frequency of mutations, most have no or very little effect on the protein synthesised in the ribosomes.

The change in protein structure is usually slight and harmless and its function or appearance is relatively unaffected.

However, certain mutations can have quite an effect on a protein with serious consequences.

This result of this genetic variant may code for a different sequence of amino acids and consequently may change the shape of the final protein structure and its activity.

e.g. theoretically, for an enzyme (protein), its activity may be increased, decreased or completely inhibited its action.

A mutation might even lead to coding for a different amino acid and hence a different protein is produced.

The protein might not be useful or potentially harmful and treated as a 'foreign' substance by the immune system.

If the protein is no longer the right shape it might not be able to perform its function e.g.

(i) an altered shape might mean an enzyme E cannot perform its catalytic action because the substrate molecules S can't lock into the active site - see diagram below (from my Enzymes - structure and functions page).

(ii) If substances like collagen, the main structural protein molecule in the connective tissues of your body, isn't formed properly, muscle tissue can be weakened or completely useless in providing physical support for an organisms body.

Genetic variants can be inherited from one generation to another e.g. mother to child.

See more on the consequences of mutations (on this page)

and  the effects of non-coding DNA (on this page)

and see evolution page for lots more notes on variation

 


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(c) What causes mutations?

Mutations are relatively uncommon, in DNA code copying, it is estimated that there is a 1 in 109 (1 in a billion) chance of a mutation, though other factors can come into play to increase this e.g. exposure ionising radiation and ingesting carcinogenic molecules..

Mutations are happening all the time and can occur quite spontaneously - a random event.

There are various different ways that mutations can occur and change the base sequence in DNA e.g.

A mutation can happen if an error occurs in chromosome replication (DNA replication) i.e. it might not be as perfect as that shown in the diagram below (see DNA and RNA structure and Protein Synthesis).

The chance of a mutation is increased if an organism is exposed to certain chemicals, particularly those known as carcinogenic substances e.g. some constituents of tobacco tar.

A carcinogen is defined as any substance (e.g. carcinogenic chemical), radionuclide, or radiation that promotes carcinogenesis, the formation of cancer.

This may be due to the ability of the substance or radiation to damage the genome or to the disruption of cellular metabolic processes.

Some molecules cause mutations by interfering with the unzipping of DNA and producing errors in the replication.

Radiation from radioactive materials is particularly effective in causing mutations, hence the dangers associated with exposure to alpha, beta and gamma ionising radiations.

The energy of the particles is great enough to break chemical bonds, inducing changes in the molecular structure of DNA.

See Alpha, beta & gamma radiation -  ,dangers of radioactive emissions - health and safety issues and ionising radiation gcse physics

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(d) Types of mutation

Deletion mutation:

A base might be deleted at random from the DNA base sequence. Usually just one base is deleted.

This will change the way in the nucleotide base sequence is read and will affect other bases further down the DNA strand.

The wrong triplets are recognised so the wrong amino acids will be coded for! So, in the diagram this section of base sequence changes from ...

... ATC GTT AGC CGA ... etc. to ... ATC TTA GCC GA. ... etc.

In other words an abnormal amino acid sequence is produced.

This will change how the base sequence of triplet codes is read in making RNA to code for a protein synthesis. The mutation will have knock on effects down the strand of DNA i.e. it may not now code for the correct sequence of amino acids to make the appropriate protein with its correct structure.

This might affect the protein's structure and inhibit is function.

The correct protein might not actually be made, with serious consequences.

 

Insertion mutation:

A new base may be inserted into the DNA base sequence into a position it should NOT occupy in a gene.

This will change the way the triplet codes are read i.e. it changes the amino acid code and code for the wrong amino acids.

In the diagram the original triplet codons are ... ATC GTT AGC CGA ... etc. but after the insertion of base T after the first triplet, the triplet codons now read quite differently ...

so this part of the base sequence becomes ... ATC TGT TAG CCG A.. ... etc.

Also, as a consequence, more than one amino acid triplet is changed because a whole sequence of bases can be affected. The wrong amino acids will be coded for.

Again, this mutation will change how the base sequence of triplet codes is read in making RNA to code for a protein synthesis. The mutation will have knock on effects down the strand of DNA and may not code for the correct sequence of amino acids to make the appropriate protein. This might affect the protein's structure and inhibit is function. The correct protein might not actually be made, with serious consequences.

One or bases may be inserted in a single mutation. If one or two bases are inserted the above applies.

BUT, if three bases are inserted, the original sequence before and beyond the insertion remains intact! Is the consequence an extra amino acid in the polypeptide-protein? Can the same functioning protein still be made?

 

Substitution mutation:

Another base in the DNA is substituted at random with a different base changing the base sequence.

Here there are two possible outcomes:

(i) there might not be any overall effect because some amino acids are coded for by more than one triplet and the substitution might make one of those other triplet codes.

e.g. in the diagram the 2nd triplet GTT mutated to ATT, but may still code for the same amino acid.

(ii) the sequence can't be read correctly because the code doesn't match the particular amino acid required.

The wrong amino acid will be coded for, or, it might not code for any amino acid at all.

Again, as with other types of mutation, how the base sequence of DNA triplet codes are read is changed, in making RNA to code for a protein synthesis. The mutation has knock on effects down the strand of DNA affecting the coding for amino acids to make the appropriate protein. This affects the protein's structure and inhibit is function and maybe the correct protein might not actually be made, with serious consequences.

See also the effects of non-coding DNA


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(e) What are the consequences of mutations?

Important reminders:

(i) Enzymes are proteins. They catalyse most reactions in organisms.

They have a specific shape and molecular structure that enables them to catalyse specific reactions.

If the enzyme protein molecule is not correctly synthesised, then it cannot perform its catalytic role in biochemistry. This is illustrated with the diagram and notes below.

enzyme structure mutation affecting active site incorrect amino acid sequence wrong damaged protein structure gcse biology igcse

A The protein structure of the enzyme is correctly formed form correctly coded DNA i.e. no mutations have had an adverse effect. The amino acid sequence correct and so the protein coils into its correct 3D structure and the active site can accept the substrate molecule.

B The chemical change can take place because the protein structure of the active site is the correct 3D shape to accept the substrate molecule which 'docks in' - the 'key and lock' mechanism.

C One or more mutations has caused a change in the amino acid sequence, leading to a change in protein shape at the active site, so the substrate molecule cannot 'dock' in and be chemically changed by the enzyme.

Note that all the rest of the enzyme structure is correct, and even if not due to a mutation affecting the amino acid sequence, it might not affect the active site. One reason why mutations do not always have a detrimental effect on the protein-enzyme structure and function.

(ii) If a mutation produces a change in the triplet codes for amino acids then the final protein formed may have a different structure and function than the one that was supposed to have been formed (this was explained in section (a) above.

The protein produced is unlikely to be able to perform the function that was intended from the DNA code.

The protein might do something different or may be incapable of doing anything.

A single mutation changing the function of a single protein molecule can have a significant effect on the phenotype.

 

Note that most mutations have no effect on an organism's phenotypes.

Some mutations can have a small effect, but there are rare mutations that can produce a new phenotype in a species - see evolution.

 

Examples:

The genetic disorder cystic fibrosis is caused by the deletion of three bases with a massive detrimental effect on the phenotype.

The 'damaged' gene codes for a protein that controls the movement of salt and water in and out of cells -semi-permeable membrane control. Unfortunately, the protein produced by the cystic fibrosis variant doesn't work correctly. The result in the individual is excess mucous production in the lungs and digestive systems and this causes difficulty in breathing and digesting food.

Some mutations have a slight effect on protein function and have a relatively small effect on the phenotype - I presume the protein molecule is sufficiently well formed enough to do its function, but perhaps not perfectly.

Mutations of coding DNA do not necessarily change the amino acid sequence of a protein.

Here, such mutations have no effect on the phenotype i.e. no effect on the characteristics of an organism.

This is in sharp contrast to the sufferers of cystic fibrosis.

 

For more details see Introduction to the inheritance of characteristics and genetic diagrams (including Punnett squares)  including technical terms, Mendel's work and inherited genetic disorders, genetic testing


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(f) Extra notes on non-coding DNA

In humans the coding for proteins is only about 1.5% of our DNA involving 20 000 to 25 000 genes, most of the rest is non-coding DNA, but it isn't there just to make up the numbers!

It appears that many sections of DNA are described as 'non-coding', meaning they do not code for any proteins.

However these non-coding sections of DNA perform other essential functions including switching genes 'on and off'.

This means whether or not a gene is expressed.

The word 'expression' in genetics means that that gene is switched on and used to make a protein that contributes to a phenotype - what is produced in a particular characteristic.

Therefore, any mutations in this non-coding DNA may prevent the synthesis of protein and the lack of this protein may adversely affect the organism's phenotype - the gene expression.

Some specific examples

Fruit flies have an enzyme XDH which is involved in producing a red pigment.

Fruit flies with normal XDH enzyme activity have red eyes.

Fruit flies with no XDH activity have brown eyes because no red pigment is produced.

So there are parts of the DNA strands that do NOT code for any proteins, but they are of great importance.

More and more scientific research is showing that some of these non-coding sections switch genes on and off, in other words, they control whether or not a gene is expressed to make a protein.

Therefore some of these non-coding regions of the DNA are involved in protein synthesis.

Before transcription can occur, the RNA polymerase has to bind to a non-coding section of DNA adjacent to the specific gene (for a specific protein).

If a mutation has occurred in this section of the DNA it can affect the ability of the RNA polymerase to bind to it - it might be harder or easier (or no effect).

The quantity and accuracy of how much mRNA is transcribed depends on how well this binding takes place - and therefore affects how well the protein is produced.

Therefore the production of the protein may be affected, and, depending on its function, that specific phenotype may also be affected.

This means that genetic variants in non-coding regions of DNA can affect the phenotypes exhibited by an organism, despite the fact that these non-coding sections of DNA done code for proteins themselves.

A summary from DNA and RNA structure and Protein Synthesis  gcse biology revision notes


 For more on this topic see

Introduction to the inheritance of characteristics and genetic diagrams (including Punnett squares) including technical terms, Mendel's work and inherited disorders - gcse biology revision notes

Inherited characteristics and human sexual reproduction, genetic fingerprinting and its uses gcse biology

 


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