Genetic Control of Protein

7/25/2019 Genetic Control of Protein

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Features of genetic molecule

Carry instructions for the construction andbehaviour of cells

The ability to be copied perfectly over andover again: nuclei of each of daughtercells

DNA= deoxyribonuleic acid

!NA=ribonucleic acid"are polymers #ith smaller molecules=

nucleotides so they are polynucleotides


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Nucleotides

$ components:"nitrogen containing base

There are five different organic bases but they all contain the elementscarbon hydrogen oxygen and nitrogen% They fall into groupspurines&t#o rings of carbon and nitrogen atoms' and pyrimidines&a single ring of carbon and nitrogen atoms'% The base thymineis

found in DNA only and the base uracilis found in !NA only sothere are only four different bases present at a time in one nucleicacid molecule%

"a phosphoric acid

"a deoxyribose &("carbon or pentose sugar'% )y convention the carbonatoms are numbered as sho#n to distinguish them from the carbon

atoms in the base% *f carbon + has a hydroxyl group &,-' attachedthen the sugar is ribose found in !NA%

)ase :Adenine &A' Cytosine &C' .uanine &.' Thymine &T' /racil &/'

Adenosine& part of AT0' 1 is adenine #ith a sugar 2oined to it

Thiamine = a vitamin

0urine: A. pyrimidines: CT/


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Nucleotides


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Nucleotide Polymerisation

Nucleotides can 2oin together by a condensation reaction &results inthe removal of #ater' bet#een the phosphate group of onenucleotide and the hydroxyl group on carbon $ of the sugar of theother nucleotide% The bonds lin3ing the nucleotides together arestrong covalent phosphodiester bonds%

The bases do not ta3e part in the polymerisation so there is asugar"phosphate bac3bone #ith the bases extending off it% Thismeans that the nucleotides can 2oin together in any order along thechain% 4any nucleotides form a polynucleotide%

5ach polynucleotide chain has t#o distinct ends

a $6 &7three prime6' end carbon $ of the deoxyribose is closest tothe end

and a (6 &7five prime6' end carbon ( of the deoxyribose is closestto the end


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Structure of DNA

The three"dimensional structure of DNA #as discovered in the 89(;s by


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DNA


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Complementary base pairing

A al#ays pair #ith T as A=T

C al#ays pair #ith . as C=.

A purine in one strand must be al#ays theopposite a pyrimidine in the other


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!NA

!NA is a nucleic acid li3e DNA but #ith >

differences:

!NA has the sugar ribose instead of

deoxyribose

!NA has the base uracil instead of

thymine

!NA is usually single stranded

!NA is usually shorter than DNA


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Function of DNA

DNA is the genetic material and genes are made of DNA% DNA

therefore has t#o essential functions: replication and expression% !eplication means that the DNA #ith all its genes must be

copied every time a cell divides%

5xpression means that the genes on DNA must controlcharacteristics% A gene #as traditionally defined as a factor that

controls a particular characteristic &such as flo#er colour' but amuch more precise definition is that a gene is a section of DNA thatcodes for a particular protein%DNA is a code for proteins determiningthe exact order in #hich the amino acids 2oin together #hen proteinsare made in a cell%

Characteristics are controlled by genes through the proteins they

code for li3e this:


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5xpression can be split into t#o parts:transcription &ma3ing !NA' and translation&ma3ing proteins'% These t#o functions

are summarised in this diagram &called thecentral dogma of genetics'%


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Replication - DNA Synthesis

=semi"conservative replication because half of the original moleculeis 3ept &conserved' in each of the ne# molecule

DNA is copied or replicated before every cell division so that one

identical copy can go to each daughter cell% The method of DNA

replication is obvious from its structure: the double helix un?ips and

t#o ne# strands are built up by complementary base"pairing onto the

t#o old strands

!eplication starts at a specific seuence on the DNA molecule called

the replication origin%

An en?yme un#inds and un?ips DNA brea3ing the hydrogen bonds

that 2oin the base pairs and forming t#o separate strands% *n the nucleus are nucleotides to #hich t#o extra phosphates have

been added #hich activate the nucleotides enabling them to ta3e part

in the next reactions

The ne# DNA is built up from the four nucleotides &A C . and T'

that are abundant in the nucleoplasm%


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These nucleotides attach themselves to the bases on theold strands by complementary base pairing%


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The Meselson-Stahl Experiment

This replication mechanism is sometimes called semi"conservative replication because each ne# DNAmolecule contains one ne# strand and one old strand%This need not be the case and alternative theories

suggested that a @photocopy@ of the original DNA couldbe made leaving the original DNA conserved&conservative replication'% The evidence for the semi"conservative method came from an elegant experimentperformed in 89( by 4eselson and Btahl% They used

the bacterium E. colitogether #ith the techniue ofdensity gradient centrifugation #hich separatesmolecules on the basis of their density%


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8% .ro# bacteria on medium #ith normal 8>N->

These first t#o steps are a calibration% They sho# that the method can distinguish bet#een DNA containing 8>N and that containing 8(N%

+% .ro# bacteria for many generations on medium #ith 8(N->

$% !eturn to 8>N-> medium for + minutes &one generation'

This is the crucial step% The DNA has replicated 2ust once in 8>N medium% The resulting DNA is not heavy or light but exactly half #ay

bet#een the t#o% Thus rules out conservative replication%


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>% .ro# on 8>N-> medium for > mins &t#o generations'

After t#o generations the DNA is either light or half"and"half% This rules out dispersive

replication% The results are all explained by semi"conservative replication%


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DNA controls protein synthesis

The seuence of bases or nucleotides in a DNA molecule is a codefor the seuence of amino acids in a polypeptide%

The code is a $ letter or triplet code: each seuence three basesstands for one amino acid% The seuence is al#ays read in oneparticular direction and on only one of the t#o strands of the DNA

molecule% The code of DNA molecule is used to determine ho# thepolypeptide molecule is constructed%

The part of the DNA molecule #hich codes for 2ust only onepolypeptide or protein =gene &$'

.enome"total set of genes in a cell& total information'

The triplet of bases of t!NA&anticodon' lin3s up #ith acomplementary triplet of m!NA& codon'


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4utation

A mutationoccurs #hen a DNA gene is damaged orchanged in such a #ay as to alter the genetic messagecarried by that gene%

The nucleotide seuence is altered thus changing theseuence of the m!NA codons% This causes the #rongamino acid to be produced resulting in a non"functionalpolypeptide% ,ccasionally there is no effect or the proteinis actually improved%

Bic3le"cell disease and Cancer are both results ofmutations%


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DNA and Protein Synthesis

Transcription - RNA Synthesis

DNA never leaves the nucleus but proteins are synthesised in thecytoplasm so a copy of each gene is made to carry the message from thenucleus to the cytoplasm% This copy is m!NA and the process of copying is

called transcription% The start of each gene on DNA is mar3ed by a special seuence of bases%

The !NA molecule is built up from the four ribose nucleotides &A C . and/' in the nucleoplasm% The nucleotides attach themselves to the bases onthe DNA by complementary base pairing 2ust as in DNA replication%-o#ever only one strand of !NA is made using one strand of the DNA as atemplate

% The DNA stand that is copied is called the template or sense strand

because it contains the seuence of bases that codes for a protein% Theother strand is 2ust a complementary copy and is called the non"template orantisense strand%

The ne# nucleotides are 2oined to each other by strong covalent bonds bythe en?yme !NA polymerase%


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,nly about base pairs remain attached at a time since the m!NAmolecule peels off from the DNA as it is made% A #inding en?yme

re#inds the DNA% The initial m!NA or primary transcript contains many regions thatare not needed as part of the protein code% These are called introns&for interruption seuences' #hile the parts that are needed arecalled exons &for expressed seuences'% All eu3aryotic genes haveintrons and they are usually longer than the exons%

The introns are cut out and the exons are spliced together byen?ymes The result is a shorter mature !NA containing only exons% The

introns are bro3en do#n% The m!NA diffuses out of the nucleus through a nuclear pore into

the cytoplasm #here is attaches to a ribosome%

*n the cytoplasm there are molecules of transfer !NA and freeamino acids &at least + molecules of t!NA' "have a triplet of basesat one end and a region #here an amino acid can attach at theother%

5ach amino acid is coded for by $ bases%


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t!NA is an adapter that matches amino acids to their codon% t!NA is onlyabout nucleotides long and it folds up by complementary base pairing toform a looped clover"leaf structure% At one end of the molecule there isal#ays the base seuence ACC #here the amino acid binds% ,n the middleloop there is a triplet nucleotide seuence called the anticodon&$ unpairedbases'% There are E> different t!NA molecules each #ith a differentanticodon seuence complementary to the E> different codons% The aminoacids are attached to their t!NA molecule by specific en?ymes% These arehighly specific so that each amino acid is attached to a t!NA adapter #iththe appropriate anticodon%


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Messenger RNA mRNA! m!NA carries the @message@ that codes for a particular

protein from the nucleus here the DNA master copy is'to the cytoplasm here proteins are synthesised'% *t issingle stranded and 2ust long enough to contain one

gene only% *t has a short lifetime and is degraded soonafter it is used%

Ri"osomal RNA rRNA! r!NA together #ith proteins form ribosomes #hich are

the site of m!NA translation and protein synthesis%

!ibosomes have t#o subunits small and large and areassembled in the nucleolus of the nucleus and exportedinto the cytoplasm%


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Translation - Protein Synthesis

8%A ribosome&rA!Nproteins'

attaches to the m!NA at aninitiation codon &A/.' formethionine%The m!NA binds tothe small subunit% The ribosomeencloses t#o codons%

+% met"t!NA diffuses to theribosome and attaches to them!NA initiation codon bycomplementary basepairing& t!NA" anticodon /AC'

$% The next amino acid"t!NAattaches to the ad2acent m!NA

codon &leu in this case'%


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>% The bond bet#een theamino acid and the t!NA is cutand a peptide bond is formedbet#een the t#o amino acids%

(% The ribosome movesalong one codon so that a ne#amino acid"t!NA can attach% Thefree t!NA molecule leaves to

collect another amino acid% Thecycle repeats from step $%

E% The polypeptide chainelongates one amino acid at atime and peels a#ay from the

ribosome folding up into a proteinas it goes% This continues forhundreds of amino acids until astop codon&/AA/AC/.A' isreached #hen the ribosome fallsapart releasing the finishedprotein%


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A single piece of m!NA can be translated by many ribosomes simultaneously somany protein molecules can be made from one m!NA molecule% A group ofribosomes all attached to one piece of m!NA is called a polysome or polyribosomes%

Bo the base seuence on the DNA molecule determines the base seuence on them!NA #hich determines #hich t!NA molecules can lin3 up #ith them%

The seuence of bases on DNA codes for the seuence of amino acids in proteins%)ut there are + different amino acids and only > different bases so the bases areread in groups of $% This gives >$ or E> combinations more than enough to code for+ amino acids% A group of three bases coding for an amino acid is called a codon andthe meaning of each of the E> codons is called the genetic code%


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Post-Translational Modification

*n eu3aryotes proteins often need to be alteredbefore they become fully functional%

4odifications are carried out by other en?ymesand include: chain cutting adding methyl orphosphate groups to amino acids or addingsugars &to ma3e glycoproteins' or lipids &to ma3e

lipoporteins'%


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5xpression can be split into t#o parts:transcription &ma3ing !NA' and translation&ma3ing proteins'% These t#o functions

are summarised in this diagram &called thecentral dogma of genetics'%


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Nuclear division

Cell reproduce by dividing and passing on

their genes to daughter cells &has its o#n

nucleus'

The nucleus al#ays divides before a cell

divides

.ametes are derived from one cell" the

?ygote&= the cell formed #hen + gametes

from parents fused'


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Chromatin and chromosomes

The DNA molecule in a single human cell is 99 cm long so is 8 timeslonger than the cell in #hich it resides &G 8mm '%

*n order to fit into the cell the DNA is cut into shorter lengths and eachlength is tightly #rapped up #ith histone proteins to form a complex calledchromatin% During most of the life of a cell the chromatin is dispersed

throughout the nucleus and cannot be seen #ith a light microscope% Atvarious times parts of the chromatin #ill un#ind so that genes on the DNAcan be transcribed% This allo#s the proteins that the cell needs to be made%

Hust before cell division the DNA is replicated and more histone proteinsare synthesised so there is temporarily t#ice the normal amount ofchromatin% Follo#ing replication the chromatin then coils up even tighter toform short fat bundles called chromosomes &in interphase'%

5ach chromosome is roughly I"shaped because it contains t#o replicatedcopies of the DNA% The t#o arms of the I are therefore identical% They arecalled chromatids and are 2oined at the centromere% &Do not confuse thet#o chromatids #ith the t#o strands of DNA%'


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Chromatin DNA histones at anystage of the cell cycle

Chromosome compact I"shaped formof chromatin formed

&and visible' duringmitosis

Chromatid single arm of an I"shaped chromosome


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#omologous $hromosomes%

matching pairs of chromosomes *f a dividing cell is stained #ith a special fluorescent dye and

examined under a microscope during cell division the individual

chromosomes can be distinguished% They can then be photographed

and studied% This is a difficult and s3illed procedure and it often helps

if the chromosomes are cut out and arranged in order of si?e%

This display is called a 3aryotype and it sho#s several features:


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Different species have different number of chromosomes but allmembers of the same species have the same number% -umanshave >E chic3ens have J goldfish have 9> fruit flies have potatoes have > and so on% The number of chromosomes doesnot appear to be related to the number of genes or amount of DNA%

The chromosomes are numbered from largest to smallest% Chromosomes come in pairs called homologous pairs &@same

shaped@'% Bo there are t#o chromosome number 8s t#ochromosome number +s etc and humans really have +$ pairs ofchromosomes%

-omologous chromosomes are a result of sexual reproduction and

the homologous pairs are the maternal &inherited from the mother'and paternal &inherited from the father' versions of the samechromosome so they have the same seuence of genes fro thesame characteristics%

,ne pair of chromosomes is different in males and females% Theseare called the sex chromosomes and are non"homologous in one ofthe sexes% *n humans the sex chromosomes are homologous infemales &II' and non"homologous in males &IK'% &*n birds it is theother #ay roundL' The non"sex chromosomes are called autosomesso humans have ++ pairs of autosomes and 8 pair of sexchromosomes%


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The position of the sex chromosomes is to on one side in3aryotype

Female has +I and male has IK

5ach chromosome has a characteristic code for differentfeatures%

The -.0 is investigating #hich genes are located on#hich chromosomes

The chromosome number is halved from the diploidnumber &+n' to the haploid number &n'% This is necessaryso that the chromosome number remains constant fromgeneration to generation% A +n body=>E

-aploid cells have one copyset of each chromosome#hile diploid cells have homologous pairs of eachchromosome%.ametes are haploid cells so has +$


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The gene for a particular characteristic is al#aysfound at the same position or locus &plural loci'on a chromosome%

A gene controlling a characteristic may exist indifferent forms &alleles'"are expressed differently

*f both homologous chromosomes have a copyof the faulty"the person #ill suffer the disease if

has only one copy of the faulty allele"termed acarrier


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T#o types of nuclear division

8%gro#th"4*T,B*B &the daughter cell 3eep

the same number of chromosomes as

parent cell'

+%sexual reproduction" 45*,B*B &halves

the chromosomes and result gamets'


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4*T,B*B

The mitotic phase can be sub"divided into four phases&prophase metaphase anaphase and telophase'%

4itosis is strictly nuclear division and is follo#ed bycytoplasmic division or cyto3inesis to complete cell

division% The gro#th and synthesis phases arecollectively called interphase &i%e% in bet#een celldivision'% 4itosis results in t#o daughter cells #hichare genetically identical daughter nuclei to each otherand is used for gro#th and asexual reproduction%

*s part of cell cycle= period bet#een one cell division andthe next and has $ phases: interphase nuclear divisionand cell division


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During interphase" a signal received that

the cell should divide again

Nuclear division follo# interphase

*n animal cells cell division involves

constriction of the cytoplasm bet#een the

t#o nuclei= cyto3inesis


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4itosis

4itosis is a type of cell division that

produces genetically identical cells%

During mitosis DNA replicates in the

parent cell #hich divides into t#o ne#cells each containing an exact copy of the

DNA in the parent cell% The only source of

genetic variation in the cells is viamutations%


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Asexual reproduction is the production ofoffspring from a single parent using mitosis% Theoffspring are therefore genetically identical toeach other and to their parent" in other #ordsthey are clones% Asexual reproduction is verycommon in nature and in addition #e humanshave developed some ne# artificial methods%The Matin terms in vivo&in life i%e% in a living

organism' and in vitro&in glass i%e% in a testtube' are often used to describe natural andartificial techniues%

Genetic Control of Protein

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