translation mutations molecular biology

8/7/2019 Translation Mutations Molecular Biology

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The consequences of mutations in

Your Favorite Gene (YGF)

TATA

Promoter

+

1

-200

UAS+

1

0

0

0

Transcription Unit

ATGCCcggaaaGUGA

Coding sequence

Exon 1 Intron 1 Exon 2

5 UTR 3 UTR

mRNA


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NON CODING regions of Your Favorite Gene (YGF)-

Promoter

TATA

Promoter

+1

-200

UAS

+1

0

0

0

Transcription Unit

ATGCCcggaaaGUGA

Coding sequence


5 UTR 3 UTR

mRNA

Mutations in the Promoter

Reduce or abolish transcription of

mRNA resulting in no protein or

reduced amount of normal orwildtype protein

Mutations in the TATA may alter the

+1 site resulting in a new

transcription start site. This may

decrease the stability of the mRNA

resulting in less wt mRNA andtherefore less wt protein.


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Terminator

TATA

Promoter

+1

-200

UAS

+1

0

0

0

Transcription Unit

ATGCCcggaaaGUGA

Coding sequence


5 UTR 3 UTR

mRNA

Mutations in the 3 UTR/Terminator

3 Untranslated region- may

decrease the stability of the mRNA

resulting in less wt mRNA andtherefore less wt protein.

Terminator sequence- will result in

longer mRNA which may decrease

the stability of the mRNA resulting in

less wt mRNA and therefore less wt

protein.


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5 UTR

TATA

Promoter

+1

-200

UAS

+1

0

0

0

Transcription Unit

ATGCCcggaaaGUGA

Coding sequence


5 UTR 3 UTR

mRNA

Mutations in the 5 UTR

5 Untranslated region-(Shine

Delgarno or Kokak sequence)

binding of the ribosome will beabolished; no translation but

normal mRNA! No protein formed!


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Introns and Splice Junctions

TATA

Promoter

+1

-200

UAS

+1

0

0

0

Transcription Unit

ATGCCcggaaaGUGA

Coding sequence


5 UTR 3 UTR

mRNA

Mutations in the Intron

VSOLFHMXQFWLRQVRU

%UDQFKSRLQW WKLVZLOOUHVXOW

LQWKHDEQRUPDOVSOLFLQJ

FDXVLQJDQDEQRUPDOP51$ XSRQ

WUDQVODWLRQWKHH[RQ

VHTXHQFHVZLOOEHQRUPDOO\

WUDQVODWHGEXWDIUDPHVKLIW

ZLOORFFXUZKHQWKHLQWURQ

VHTXHQFHVDUHWUDQVODWHG

Other intron sequences- shouldnot alter splicing resulting in


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The consequences of mutations in CODING regions of

Your Favorite Gene (YGF)-

TATA

Promoter

+1

-200

UAS

+1

0

0

0

Transcription Unit

ATGCCcggaaaGUGA

Coding sequence


5 UTR 3 UTR

mRNA

mRNA

Mutations in the coding

sequences-

These mutations alter the qualityof the protein

mRNA regulation, abundance and

size is normal

The coding sequence is altered so

that the protein amino acid

sequence is changed!


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mRNA

We use special terms to refer to the type of mutation that

alters the quality of the protein.

These terms only refer to mutations in the CODING

SEQUENCE! Not mutations in the promoter or

terminators.!


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full length protein& functional

mRNA

Wildtype THE ONE BIG FLY HAD ONE RED EYE

Silent THEONE BIG FLY HAD ONE RED EYE

A silent mutation alters the DNA sequence but still codes for the

same amino acid so the resulting protein is identical.

CUU vs CUA both code for the same amino acid Leucine.


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Your Favorite Gene (YGF)-full length protein but

nonfunctional

mRNA


THI ONE BIG FLY HAD ONE RED EYE

CONSERVATIVE MISSENSE - REPLACE LIKE AMINO ACID

FOR LIKE AMINO ACID, CHARGED FOR CHARGED,

HYDROPHOBIC FOR HYDROPHOBIC.

NONCONSERVATIVE MISSENSE- REPLACE UNLIKE AMINO

ACID FOR UNLIKE AMINO ACID. An example is Sickle cell

anemia where a glutamic acid is replaced with valine .

THQ ONE BIG FLY HAD ONE RED EYE


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Temperature sensitive

mRNA

Some missense mutations are temperature sensitive:They show no phenotype at normal temperature

(permissive) but show a phenotype at the restricted

temperature (usually elevated)


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Temperature sensitive

How does this happen?

At 37rC The wildtype protein has a normal

stucture and has 100% activity.

At 42rC, the interactions causing the wt structure

are weakened and the protein has a slight

structural change resulting in 85% activity.

At 37rC, due to the amino acid substitution(missense mutation), the mutant has an altered

structure rsulting in a decrease in activity to 60 %

of wildtype. The mutant may have a slight

phenotype such as slow growth

At 42rC, the interactions causing the mutant

structure are weakened and the protein has a

structural change resulting in 10% activity. This

activity is insufficient to allow the protein to

function and results in strong phenotype (no

growth and the process stops.)

at 37rC

WT protein 100%

at 45rC

WT protein 85%

at 37rC

Mut protein 60%

at 45rC

Mut protein 10%


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Your Favorite Gene (YGF)- Shortened protein

mRNA


NONSENSE THE ONE BIG stop

a codon is replaced with a stop codon.Shortened

protein; Function depends on how much of the wildtype amino acids

remain.

FRAMESHIFT THE ONE QBI GFL YHA DON

Insertions or deletions that are not multiples of 3 alter the reading frame.

The amino acid sequence after the frameshift is garbage and often a

stop codon is encountered that shortens the polypeptide. Function

depends on how much of the wildtype amino acid sequence remains

before the shift.


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mRNA


DUPLICATION THE ONE BIG FLY FLY HAD ONE RED EYE

A duplication repeats a portion of the coding sequence. If it is in

multiples of 3 it does not alter the code but will add an additional amino

acid. Depending on what aa is added and where it is in the tertiary

structure will dictate the consequences of a single aa insertion.


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mRNA


EXPANDING THE ONE BIG FLY FLY HAD ONE RED EYE

THE ONE BIG FLY FLY FLY HAD ONE RED EYE

THE ONE BIG FLY FLY FLY FLY HAD ONE RED EYE

An expanding mutation expands with each generation. Since these are

usually triplets, it adds additional amino acids to the protein. Expansion

beyond a threshold are associated with a series of diseases- including

Fragile X syndrome and Huntingtons Disease.

translation mutations molecular biology

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