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164 Cards in this Set
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Recombination |
The term used for crossing over is recombination. Recombination can occur between any two genes on a chromosome, the amount of crossing over is a function of how close the genes are to each other on the chromosome.
Crossing-over occurs during Prophase I - Forms gametes Ab & aB instead of AB & ab Linkage can be ‘broken’ (disrupted) by crossing over!!!!! |
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Frequency of Crossovers |
If two genes are far apart, for example at opposite ends of the chromosome, crossover and non-crossover events will occur in equal frequency. Genes that are closer together undergo fewer crossing over events and non-crossover gametes will exceed than the number of crossover gametes. For two genes are right next to each other on the chromosome crossing over will be a very rare event.
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Genes: Close or Far |
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Possible types of gametes on Chromosomes |
Two types of gametes are possible when following genes on the same chromosomes. If crossing over does not occur, the products are parental gametes. If crossing over occurs, the products are recombinant gametes. |
with or without crossovers |
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Allelic composition of parental and recombinant depends on: |
The allelic composition of parental and recombinant gametes depends upon whether the original cross involved genes in coupling or repulsion phase. |
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Coupling vs. repulsion |
Coupling (or Cis Phase) - two dominant alleles are contributed by the same parent (eg, AABB x aabb). Repulsion (or Trans)- two dominant alleles are contributed from the opposite parents (eg, AAbb x aaBB). Coupling and repulsion have different ratios and different error rates in the F2, so they have to be dealt with separately. Coupling is always first |
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Linkage, Linkage group and what law it violates |
Linkage = refers to a situation where genes are located on the same chromosome and are inherited together Linkage violates Law of Independent Assortment Designation of Linkage AB/ab = coupling (cis) configuration Ab/aB = repulsion (trans) configuration Linkage Group = a group of genes that are inherited together Linkage can be ‘broken’ (disrupted) by crossing over!!!!! |
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Challenge: If one considers a chromosome as a huge linkage group, how many linkage groups are in human males? Females? |
Males = 24 —> 22 autosomes & XY Females = 23 —> 22 autosomes & X |
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Describe an unlinked gene and linked gene |
Unlinked genes are on a different chromosome and segregate independently into gametes. Linked genes are on the same chromosome An individual of genotype AaBb where loci A and B are unlinked will produce the following gamete types in EQUAL frequency: AB, Ab. aB, ab |
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Genetic recombination produces what? |
RECOMBINANTS , progeny that shows nonparental recombinations. |
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What is used to determine which genes are linked to each other ? |
Test crosses |
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Genetic mapping provides information , can you name such an example of information that can be attained? |
locations of genes on chromosomes Useful in recombinant DNA research Investigate genes and their functions |
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Match a. Gene Marker b.DNA marker c. Genetic marker 1. mutation or varient gives a distinguish able phenotype 2.Alleles of genes 3.Polymorphic |
a.2 b.3 c.1 |
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1) DO Physical maps depend on the exchange of homologous chromosomes parts during meiosis by crossing over. 2) What percentage is expected of recombinant phenotypes in independent assortment |
1) No 2) 50% |
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State the Law of Independent assortment of gene pairs |
Genes on different traits assort independently of one another in the production of gametes. |
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recombinants are produce as a result of a process called.. |
crossing over |
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The closer the genes are the(less or more) likely there will be a recombination event between them |
the closer the genes are the less likely recombination occurs between them |
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If incomplete linkage what has occured |
crossing over |
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If there is less than 50% recombinant phenotypes what does that tell you about the genes ? |
INDICATES LINKAGE OF THE GENES |
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What stage does crossing over occur at? |
The Four chromatid stage in prophase 1 in meiosis |
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The study of corn by Harriet Creighton and Barbara McClintock studied what kind of genes? |
X linked genes that have different shape |
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If genes are linked as AB/ab what gamete types will occur and at what frequency? |
If genes are linked as AB/ab then the following gamete types will occur if there is crossing over: AB & ab (high frequency) —> parental Ab & aB (low frequency) —> recombinant |
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If Recombinant gametes are found in the lowest frequency. Is the direct result of...? |
Recombinant: gametes that are found in the lowest frequency. This is the direct result of the reduced recombination that occurs between two genes that are located close to each other on the same chromosome. |
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Coupling phase cross prevalent gametes? Repulsion phase crosses prevalent gametes? |
For a coupling phase cross, the most prevalent gametes will be those with two dominant alleles or those with two recessive alleles. Repulsion phase crosses, gametes containing one dominant and one recessive allele will be most abundant. |
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Order of frequency for? No crossover = most frequent Single crossover (sco) = frequent (but not as much as no crossover) Double crossover (dco) = least frequent |
No crossover = most frequent Single crossover (sco) = frequent (but not as much as no crossover) Double crossover (dco) = least frequent
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Double Cross over |
Double Cross over: two separated cross overs events between 2 loci, more frequent between genes that are far apart. |
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Parsimony |
Parsimony = simplest explanation is most likely preferred |
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Recombination frequencies cannot exceed ? |
Recombination frequencies = cannot exceed 50% —> at 50% recombination independent assortment (unlinked) is indicated One can obtain 50% recombinants under linkage when the loci are very far apart (special circumstance) |
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Rule for probabilities of crossovers |
Rule = the more the distance between 2 loci, the more the probability of crossing over between them |
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Linkage map units for measurements? Physical map? |
Can use observation to map the relative distances between loci Produces a linkage map —> unit of measure = centiMorgan (cM) or map unit (m.u.) which equals 1% recombination Physical map = real distances |
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1st evidence for crossing over came from what experiment? |
Corn Harriet and McClintock |
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2nd Evidence for crossing over was from ? |
Curt Stern on Drosophilia melanogaster |
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The proof that genetic recombination occurs when crossing over takes place during meiosis came from what sort of experiments? |
Experiments in which the parental chromosomes differed with respect to both the genetic and cytological markers. |
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Experiments in which parental chromosomes differed with respect to both the genetic and cytological markers showed what about the markers invovled? |
that whenever recombinant phenotypes had occured the cytological markers indicated that crossing over had also occured. |
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If there are too many parental phenotypes and too few recombinants and this deviation is significant what does that tell you about the linkage of the genes? |
they are linked |
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crossing over occurs between what type of chromosomes? |
Crossing over ONLY occurs between homologous chromosomes. Non-homologous crossover may be considered as a drastic mutation its very rare and causes unbalance recombination |
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Does Frequency of recombinants changes depending on arrangements of the genes on the chromosomes? |
Frequency of recombinants is the same no matter how genes are arranged relative to each other on the chromosome |
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Two point test cross are used to determine what? |
the relative number of parental and recombinant progeny |
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In a two point test cross, the value of recombinations is more accurate if genes are closer of further apart on the chromosome.. |
close together |
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The actual phenotypes in a two point test cross depends on what? |
two allelic pairs in the homologous chromosomes are in coupling (cis) or in repulsion( trans) |
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A)Can multiple cross overs occur? B) For any test cross can recombinants exceed 50%? c) how are genes unlinked( 2 ways) d) are cross overs randomly arranged or sequently arranged along a chromosome? |
A) yes b) no c)seperate chromosomes and due the distance apart from each other d)randomly |
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Single Cross over = how many recombinants Double cross over =how many recombinants Triple Cross over=how many recombinants Four srtrand cross over= how many recombinants |
2 0/4 2/4 4/4 |
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A)In order to get an accuate map distance we can study genes that are closer or farther apart? B) 3 POINT TEST CROSSED ARE USED FOR? |
a) closer b) MONITORING DOUBLE CROSS OVERS AND DETERMINING THE RECOMBINATION FREQUENCY |
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Genophore |
prokaryotic chromosome |
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Plasmid |
Plasmids = extra chromosomal DNA, circular, small
Some are episomes and can reversibly bind to host chromosome |
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Mechanisms of Horizontal Transmission |
Is cell to cell contact required? Live or not? Are viruses required? Degree of recombination in recipient cell? |
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Transformation |
- Direct uptake of DNA by a cell from the environment - Cells are called competent cells - Doesn’t require cell to cell contact - One cell dies, one cell lives |
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Two-Point Test Cross |
1 - Make heterozygous parent 2- Breed with homozygous recessive (test cross) 3 - Tabulate progeny phenotypes 4 - Determine recombinant and parental progeny 5 - Calculate the proportion of progeny that is recombinant 6 - Then calculate the recombinant frequency |
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Three-Point Test Crossing |
- consider 3 loci at the same time 1 - Make heterozygous parent (AaBbCc) 2 - Test cross heterozygous parent with homozygous recessive (aabbcc) 3 - Observe and count progeny (large samples are required) 4 - From progeny types and counts deduce the distances |
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Expected 2CO Coincidence (C) Interference |
Expected 2CO = (Internal 1 dist) 8 (Internal 2 dist)* ( Total offspring) Coincidence (C) = observed dco/ expected dco Interference = 1 – C |
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LOD Score |
LOD Score = look at pedigrees; value of 3 or larger indicates linkage |
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Conjugation |
process by which onebacterium transfers genetic material to another through direct contact. During conjugation, one bacterium serves as the donor of the genetic material, and the other serves as the recipient. The donor bacterium carries a DNA sequence called the fertility factor, or F-factor. |
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F+ —> F- Conjugation |
1- All conjugation types require cell to cell contact 2 - All have a donor cell (F+) and a recipient cell (F-) 3 - Only makes copies of itself 4 - F = fertility plasmid 5 - Conjugation tube = pilus 6 - F+ cell = has plasmid 7 - Transfer of one template (F+) strand 8 - F- cell = lacks plasmid 9 - F+ mates with F- = 2 F+ cells 10 - F+ stays F+ 10 - F- becomes F+ |
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Hfr |
High frequency of recombination a bacterial cell with F plasmid integrated to its chromosome, thus the F plasmid of donor is not a free plasmid |
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Hfr Conjugation
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Good for genetic variability 1- High frequency of recombination 2- F plasmid integrates itself into the host chromosome 3- Hfr mates with F- = Hfr and F- 4 - Hfr stays Hfr 5 - F- stays F- 6 - Hfr = donor cell 7- F- = recipient cell |
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F’ Conjugation |
High rates of recombination 1 - Sexduction 2 - Only F plasmid is transferred, just like F+ —> F- Conjugation 3 - However, the F plasmid reversibly binds to the chromosome first 4 - F’ mate with F- = F’ and F’ merozygote 5 - F’ = donor cell 6 - F- = recipient cell 7 - Donor F' stays F' 8 - Recipient F- becomes F' ( and may produce merozygote --> a partial diploid: heterogenotes) MATE of: F' cell = F' a+ b+ c+ F- cell = a- b- c- Result = F' cell = F' a+ a- b- c- (partial diploid)
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Merozygote |
Merozygote --> a partial diploid: heterogenotes |
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Transduction |
1- Transfer of genetic material from one cell to another via a viral vector 2- Doesn’t require cell to cell contact 3 - Generalized, specialized 4 - Occurs in both eukaryotic and prokaryotic cells |
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R Plasmids |
R = resistance Mechanism of Antibiotic Resistance 1 - Binds to antibiotic, disabling it 2- Binds to antibiotic target, protecting it 3 - Transport protein that expels antibiotic from the cell |
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Viruses |
- Intracellular parasites - Probably evolved from episomes - Nucleic acid core - Protein coat or capsid - Double stranded or single stranded DNA/RNA - Single stranded RNA = reverse transcriptase – retrovirus – HIV - Highly specific - Bacteriophages = viruses that are specialized to attack bacteria |
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Envelope Viruses |
- Lipid bilayer outside of capsid - Derived from host cell - Gives an added layer of protection of the nucleic acid core - Helps to attach to the host cell |
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Bacteriophages |
- Bacteriophages = viruses that are specialized to attack bacteria - Transfer genetic material by transduction |
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Lytic Cycle |
- Undertaken by virulent viruses Ex: bacteriophage 1 - Attachment 2 - Penetration of genetic material 3 - Make viral components 4 - Assembly 5 - Lysis (release virion) |
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Virus and Virion |
Virus: inside host cell (without capsid or envelope) Virion: outside host cell (contain capsid and envelope) |
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Lysogenic Cycle |
- Undertaken by temperate virus - Process = lysogeny Ex: HIV 1 = retrovirus 1 - Attachment 2- Penetration of genetic material 3- Genetic material incorporated into host chromosomes a) Provirus = virus incorporated into eukaryotic chromosome b) Prophage = virus incorporated into prokaryotic chromosome 4 - Release 5 - Can go into lytic cycle and destroy cell before leaving |
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Provirus vs Prophage |
a) Provirus = virus incorporated into eukaryotic chromosome b) Prophage = virus incorporated into prokaryotic chromosome |
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Generalized Transduction |
Generalized Transduction mediated by lytic phages - Any piece of DNA from host cell can be transferred - Undertaken by virulent and temperate viruses |
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Specialized Transduction |
Specialized Transduction mediated by lysogenic phages - Specific DNA fragments - Only DNA adjacent to insertion site can be transferred - Need lysogeny - Undertaken by temperate viruses |
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Prions |
- Proteins that can reproduce on their own and become infectious - Infective proteins - Causes spongiform encephalopathy - Proteins stack together in Golgi making plaques - Named in 1982 —> from the words protein and infection - Normal prion: PrPc (Normal folding pattern) - Mutant prion: PrPsc (alpha helix relaxed into a beta sheet) - VIOLATION to central dogma: changes of shapes instead of changes in amino acids |
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Spongiform Encephalopathy (Animals) |
- Scrapie = sheep and goats - Transmissible Mink Encephalopathy (TME) = mink - Chronic Wasting Disease (CWD) = deer, elk, moose - Bovine Spongiform Encephalopathy (BSE) = cattle (Mad Cow Disease) - Feline Spongiform Encephalopathy (FSE) = cats |
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Spongiform Encephalopathy (Humans) |
- Creutzfeldt-Jacob Disease (CJD) - Variant Creutzfeldt-Jacob Disease (VCJD) - Gerstmann-Straussler-Scheinker Syndrome (GSS) - Fatal Familial Insomnia (FFI) - Kuru - Alpers Syndrome |
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Human Chromosomes |
Metacentric = chromosome 1 Submetacentric = 2-12, 16-20, X, Y chromsomes Acrocentric = 13, 14, 15, 21, 22 |
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Banding Patterns I: G banding |
Use banding patterns to make ideogram - G banding - Identifies patterns when chromosomes are exposed to Giemsa stain - Distinguishes areas rich in nitrogenous bases A and T - Most common technique |
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Banding Patterns I: R banding |
Use banding patterns to make ideogram - R banding - Staining reverses light and dark pattern of G bands - Identifies regions rich in nitrogenous bases C and G |
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Banding Patterns I: Q banding |
Use banding patterns to make ideogram - Q banding - Staining with Quinacrine mustard - Viewing under UV light |
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Preparing a Karyotype |
Preparing a Karyotype Organized profile (picture) of a person's chromosomes; evaluates sizes, shapes and numbers - Metaphase cells are needed because they have maximum condensation (Breaking of spindle apparatus, interferes with microtubules) - Need cells that have a nucleus; most often WBC - Humans cannot use RBC because they lack nucleus 3q 12.2: chromosome 3, Long arm, position 12.2 3p 11.2: chromosome 3, Short arm, position 11.2
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Mutations |
- Heritable changes to DNA 1) Point mutations —> changes to individual base pairs 2) Chromosomal mutations —> changes to parts of chromosomes or entire chromosomes a) Somatic cells (occurs in body cells, it can not pass it on) b) Germ-line cells = produce sperm and egg (transmitted to offspring); fertilization |
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Chromosomal Mutations I Rearrangements |
Rearrangements = change the structure of individual chromosomes. May be: 1 - Balanced = chromosomal set has normal compliment of genetic material 2 - Unbalanced = additional or missing material 3 - Stable rearrangements can be passed on to offspring 4- Unstable rearrangements cannot be passed on to offspring |
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Types of Rearrangements Duplications |
Duplications 1- Part of chromosome is doubled or more 2- Unbalanced and stable 3- Most often due to unequal crossing over during Prophase I 3- May lead to phenotypic effects —> probably due to imbalances in gene product that affect development |
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Types of Rearrangements Duplications Types of Duplication |
- Tandem duplication = next to each other - Displaced duplication = not located adjacent to each other - Reverse duplication (inverted) = sequence is duplicated and inverted |
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Types of Rearrangements Deletions |
1 - Loss of chromosomal segment 2- Unbalanced and stable 3 - Most often due to unequal crossing over during Prophase I 4 - Can also be due to chromosome breakage 5 - Heterozygous individual may have many phenotypic effects due to: a) Gene product imbalance b) Pseudodominance = recessive alleles on the normal chromosome may be expressed (fake dominance) c) 2 copies of a gene may be needed for normal expression (gene is said to be haploinsufficient) - A--a should show A after deletion occurs to A the a phenotype will show Example: Cri-du-Chat Syndrome - Cry like a cat - Due to deletion of chromosome 5 (5p) |
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Types of Rearrangements Inversions |
1 - Balanced 2 - May be stable or unstable 3 - Involves the turning around of a chromosome segment (inversion) 4 - Alters the position and sequence of the gene (reversed order) 5 - Can be Pericentric = inversion will have a centromere included 6 - Can be Paracentric = inversion does not have a centromere included |
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Crossing Over in Heterozygote with a Paracentric Inversion Types |
Crossing Over with a Paracentric Inversion - Inversion does not have a centromere included - Can lead to abnormal gametes - Acentric = no centromere; doesn’t get passed on, will be destroyed - Dicentric = 2 centromeres on 1 strand; will be destroyed (2 spindles will attach) - 50% decrease in fertility |
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Crossing Over in Heterozygote for a Pericentric Inversion
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- Inversion will have a centromere included - 50% decrease in fertility |
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Types of Rearrangements Inversions Inversion Phenotypic Effects |
- Many inversions are associated with abnormal phenotypic effects - Why would this be if an inversion is balanced? --> Position effect = many genes are regulated in a position dependent manner; if their positions are altered they may be expressed at inappropriate times or in inappropriate tissues |
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Types of Rearrangements Translocation |
1- Transfer of a chromosome segment to another non-homologous chromosome 2 - May be reciprocal or nonreciprocal 3- May be balanced or unbalanced 4 - May result in abnormal phenotypes because of: a) Position effects (transferred region may expose genes to a new regulatory mechanism) b) Breaks may occur in a gene and affect its functioning |
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Types of Rearrangements Translocation Types of Translocation Robertsonian Translocation |
Robertsonian Translocation - Exchange between 2 acrocentric chromosomes that results in one metacentric or submetacentric chromosome and a fragment - Causes 4% of down syndrome found in humans - 2 most common in humans = 13q with 14q and 14q with 21q |
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Types of Rearrangements Translocation Types of Translocation Fragile Sites |
Fragile Sites - Regions of chromosomes that appear to be “hanging by a thread” - Most studied is on human X chromosome --> Fragile X Syndrome = most common cause of inherited mental retardation in humans - Caused by CGG trinucleotide repeat (anticipation) |
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Chromosomal Mutations II Aneuploidy |
Aneuploidy - Possessing more of fewer individual chromosomes - May arise from: --> chromosome loss meiosis (most common) --> nondisjunction |
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Chromosomal Mutations II Types of Aneuploidy |
- Nullisomy = 2n – 2 (loss of both members of homologous pair) - Monosomy = 2n – 1 (happens in humans) = 46 chromosomes - Trisomy = 2n + 1 (happens in humans) = 47 chromosomes = most common - Tetrasomy = 2n + 2
* Having extra chromosomes causes miscarriages (most common 16) * Affects phenotypes by altering dosage (too much or too little) * Occur in humans and some result in live births * Most common live birth aneuploids in humans involve the sex chromosomes (dosage, composition) * Chromosomes 13, 18, and 21 = most likely to lead to live birth aneuploidy |
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Chromosomal Mutations II Types of Aneuploidy Effects |
* Having extra chromosomes causes miscarriages (most common 16) * Affects phenotypes by altering dosage (too much or too little) * Occur in humans and some result in live births * Most common live birth aneuploids in humans involve the sex chromosomes (dosage, composition) * Chromosomes 13, 18, and 21 = most likely to lead to live birth aneuploidy |
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Chromosomal Mutations II Aneuploidy Types of Aneuploidy Sex Chromosomes Aneuploides |
- Kleinfelter Syndrome - Turner Syndrome - Metafemale - Metamale |
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Chromosomal Mutations II Aneuploidy Types of Aneuploidy Sex Chromosomes Aneuploides Kleinfelter Syndrome
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- 2N = 47, XXY (or 48, XXXY or 49, XXXXY) - Males - Has Barr bodies (is exception to the rule that only females have them) - Some may be sterile - Trisomy (2n + 1) - Breast development, tall, lanky, small penis and testes |
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Chromosomal Mutations II Aneuploidy Types of Aneuploidy Sex Chromosomes Aneuploides Turner Syndrome
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- 2N = 45, XO - Females - No Barr bodies; single X chormosome - Partially fertile - Monosomy (2n - 1) - Short, broad chest, lack of sexual development - Structure and sexual developments can be treated with hormones - Pseudoautosomal region = some parts of X chromosome not turned off |
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Chromosomal Mutations II Aneuploidy Types of Aneuploidy Sex Chromosomes Aneuploides Metafemale |
- 2N = 47, XXX (or 48, XXXX, etc.) - Trisomy (2n - 1) - 2 Barr bodies |
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Chromosomal Mutations II Aneuploidy Types of Aneuploidy Sex Chromosomes Aneuploides Metamale |
- 2N = 47, XYY - No Barr bodies - Trisomy (2n - 1) - Tall, lanky, and have lots of acne |
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Chromosomal Mutations II Aneuploidy Types of Aneuploidy Autosomal Chromosomes Aneuploides |
- Edward’s Syndrome - Patau Syndrome - Down Syndrome |
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Chromosomal Mutations II Aneuploidy Types of Aneuploidy Autosomal Chromosomes Aneuploides Edward’s Syndrome |
- Trisomy 18 - Boy: 47, XY (47, XY, +18) - Girl: 47, XX (47, XX, +18) - Joints are bent, sloping forehead, have larger ears when compared to the head |
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Aneuploidy Types of Aneuploidy Autosomal Chromosomes Aneuploides Patau Syndrome |
- Trisomy 13 - Boy: 47, XY (47, XY, +13) - Girl: 47, XX (47, XX, +13) - Major facial reconstruction (cleft lip or palate, extra fingers, eye fused, mental retardation... etc..) |
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Aneuploidy Types of Aneuploidy Autosomal Chromosomes Aneuploides Down Syndrome |
- Trisomy 21 - Boy: 47, XY (47, XY, +21) - Girl: 47, XX (47, XX, +21) - Not inherited, accident in meiosis --> Incident of Occurrence Correlated with Maternal Age |
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Aneuploidy Types of Aneuploidy Autosomal Chromosomes Aneuploides Down Syndrome Incident of Occurrence Correlated with Maternal Age |
- Incident of Occurrence Correlated with Maternal Age ---> Arrested oocytes in meiosis I may lead to mitotic spindle breakdown with increasing age --> Mechanisms that cause rejection of abnormal zygotes do not work later in life
** Mostly maternal and meiosis I = where nondisjunction happens** |
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Polyploidy |
Polyploidy: Possessing extra entire sets of chromosomes (3N = triploidy, 4N = tetraploidy) May be: - Autopolyploid = sperm and egg from same species form zygote - Allopolyploid = sperm and egg from different species form zygote
Triploid condition = enlarged head Uniparental Disomy Both chromosomes of homologue pair come from 1 parent |
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Autopolyploid Allopolyploid Uniparental Disomy |
Autopolyploid = sperm and egg from same species form zygote -- Ex: Altotetrapoid: of A= A+A+A+A
Allopolyploid = sperm and egg from different species form zygote -- Ex: Allotripoid: of A and B = A+A+B or B+B+A
Uniparental Disomy Both chromosomes of homologue pair come from 1 parent only -- Ex: Father Ff and Mother Mm Offspring will be either: --> FF: Isodisomy --> Ff: Heterodisomy ** Mother's chromosome disappear |
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Mosaicism |
- Cells within the same person have a different genetic makeup - Different arrangements or differente number's of chromosome -Some cells are normal and some are abnormal - Earlier development of nondisjunction occurs the more severe phenotypic effects (more cells are affected) - Happens after fertilization |
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DNA |
- Deoxyribonucleic acid
- Deoxyribose sugar = has OH on carbon 3’ and H on carbon 2’
- Bases = A, C, T, G |
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RNA |
- Ribonucleic acid
- ribose sugar = has OH on carbon 3’ and 2’
- Bases = A, C, U, G |
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Nucleic Acid |
- Heteropolymers of nucleotides (5) - Heteropolymers = different monomers joined by covalent bonds
- Negatively charged phosphate group, pentose sugar, nitrogenous base
Bases: -- Pyrimidines = single ring —> C, T, U -- Purines = two rings —> A, G
- Phosphodiester linkage = bonds in sugar phosphate backbone
- Antiparallel complimentary strands Base complimentary: G and C = 3 hydrogen bonds A and T = 2 hydrogen bonds
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Heteropolymers |
Heteropolymers = different monomers joined by covalent bonds |
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DNA forms |
A form DNA = observed in lab under certain conditions, right handed helix, more compact, shorter and wider
B form DNA = right handed helix, less compact, seen in living cells, 10 base pairs per 360 turn
Z form DNA = left handed helix, less then 10 base pairs |
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1928 – Frederick Griffith |
- Isolated different strains of Streptococcus pneumoniae (Type I, II, III, etc.) - The virulent (disease-causing) forms of a strain are surrounded by polysaccharide coat, which makes the colony appear smooth on agar plate = S (smooth) - Found virulent forms sometimes mutated to nonvirulent forms, that lack a polysaccharide coat and produce a rough appearing colony = R (rough) ---> Transforming principle: Substance responsible for transformation; DNA is the transforming principle in the mouse scenario |
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Walter Sutton & T.H. Morgan |
- The behavior of chromosomes during meiosis mirrored the behavior of Mendel’s “factors” - Transforming principle was located on the chromosomes; BUT chromosomes are made of DNA --> This provided the first evidence that DNA is the genetic material, which went against the hypothesis that the genetic material is protein |
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Hershey and Chase |
- Perfect test model = T2 virus (bacteriophage) that infects E.coli; made of DNA and protein - Protein coat was labelled radioactively: phage DNA = 32P (phosphorus) and protein = 35S (sulfur) - Used isotopes (radioactive forms) to follow the fate of the DNA and protein during phage infection - Used blender to shear off protein coats then a centrifuge to separate protein from cells; after centrifugation, infected bacteria form a pellet (more dense) containing DNA in the bottom of the tube and protein was found in the supernatant (less dense) Found that DNA, NOT protein, enters the bacterial cell during phage reproduction and that ONLY DNA is passed on to progeny phages
--> PROVED: DNA is the genetic information
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Maurice Wilkins |
- Used X-ray diffraction (crystallography) = X-rays beamed at molecule are reflected in specific patterns that show the structure of the molecule |
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Rosalind Franklin (DNA) |
- Used X-ray crystallography and found structure and shape of DNA
---> Chargaff’s Rules: SAME amount discovered [A] = [T] , [C] = [D]
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Watson and Crick |
James Watson and Francis Crick wanted to find out why same quantity= in order to be [A] = [T] , [C] = [D] A needs to be connected to T and C needs to be connected to G - They used existing information about the chemistry of DNA and building molecular models to discover the 3D structure of DNA |
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Chromosome Structure |
- DNA must be packaged - Cells have lots of DNA - Typical human cell has 3 billion base pairs of DNA, accounting for approximately 6ft. Supercoiling: - Relaxed B DNA has 10 base pairs per 360° turn - Most DNA is not relaxed, instead is supercoiled - Positive supercoil = in the direction of right handed coil - Negative supercoil = in the direction opposite to the right handed, of left handed coil -- Most DNA is negatively supercoiled Topoisomerases I and II relax DNA Topoisomerases I cut phosphodiester bond of one strand Topoisomerases II cut phosphodiester bond of both strands Ex: DNA gyrase (Prokaryotes only) |
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Bacterial Chromosome |
- Genophore - - Circular, single, no histones Found in nucleoid region (not membrane bound) - Associated with proteins (non-histone) - Packaged as a series of loops - Also found in mitochondria and chloroplasts |
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Eukaryotic Chromosome |
- Linear - Found within the nucleus - Chromatin = DNA and protein --- Heterochromatin = tightly packed; not expressed ---- Euchromatin = not tightly packed; expressed
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Proteins Associated with Euchromatin Chromosomes |
- Proteins = histones (H1,H2A, H2B, H3, H4) - Nucleosome = 2* (H2A, H2B, H3, H4) (8 histone proteins) form a histone octet; DNA is wound around histones - Histones have basic amino acids - Chromatosome = H1 and nucleosome
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Non-histone chromosomal proteins |
- Structural roles = scaffold proteins
- Genetic roles = activators, repressors, transcription factors, polymerases
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Order of chromosome formation |
--> Chromosome Package - Double-stranded helical structure of DNA - Nucleosomes - Chromatosome - Fold into 30 nm fiber - Forms loops averaging 300 nm fiber in length - 300 nm fibers compresses and folds into 250 nm wide fiber - Tight coiling makes the chromatid - Two chromatids join at the centromere and form chromosome |
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Centromere |
- Heterochromatin - Sequences where kinetochores attach - Particular sequences repeated many time - Can be diffused or localized - Localized centromeres may be point (small) or regional (large)
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Telomere |
- Located at the ends of chromosomes - Heterochromatin - Repeated units (hundreds to thousands of times) of 5’ – Cn (A or T)m – 3’ N = 2 or greater M = 1 – 4
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Variation in DNA sequences |
- C value = measure of the amount of DNA expressed (in haploid) - Denaturation/ renaturation of DNA (break H bond, separate strands) - Melting temperature and CG pairs ---> Melting temperature (Tm) (°C) Temperature where 50% of DNA molecules in the sample are denatured (made into single strands) - Hybridization |
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Types of DNA Sequences |
- Unique – sequence DNA (solitary genes, typical of prokaryotes) - Gene families (ex: globin gene family: myoglobin, hemoglobin α, hemoglobin β) (duplication) - Pseudogenes = nonfunctional duplicated genes - Repetitive DNA - Transposons |
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Types of DNA Sequences Repetitive DNA types |
- Moderately repetitive (150 – 300 base pairs) a) Repeated 1000’s of times Ex: rRNA genes b) Tandem repeats c) Interspersed repeats --> SINE (short interspersed repeats) (Alu) = about 300 base pairs long, (transposable element); makes up 11% of human genome; over 1 million copies --> LINE (long interspersed repeats) = more than 300 base pairs; makes up 17 % of human genome - Highly repetitive a) Satellite DNA (less than 10 base pairs) b) Repeat many times Ex: minisatellites used in DNA fingerprinting
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Transposons |
- Jumping genes - Barbara McClintock (in maize) - Different types - Can cause damage if sequence inserts in a coding region or promoter region |
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True exception to the central dogma |
Prions |
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Non Nuclear DNA of Eukaryotes |
- Found primary: --> Chloroplasts: cpDNA can not leave on its own but its believed that one day it did: Endosymbiotic hypoteses: Cyanobacteria
--> Mitochondria: mtDNA can not leave on its own but its believed that one day it did: Endosymbiotic hypotesis: alpha proteobacteria
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Human Mitochondria DNA |
- dsDNA: located inside mitochondria organelles, exists in multiple copies, in humans many per cell - maternal inherited - Circular - divide independently - Two strands: --> Heavy (outer H strand) - more guanine --> Light (inner L strand) - more cytosine - few non-coding sequences (region called D-loop) - No introns, no 5'CAP, some Poly A tail - No histones - Have non-universal codon (UGA stop in mitochondrial codes for Tryptophan) - Stop in mitochondria is signal by PolyA tail on mRNA (end wit either UA or U) - Replication uses DNA poly gamma - 2 oringes of replication: ORI H and ORI L - Transcription one promoter per strand (in D LOOP) - Each strand is transcribed includes: 22 tRNA, 13mRNA, and 2 rRNA - Translation uses f-MET, more woobles, less tRNA - Replicative Segregation of Heteroplasmic (combination of normal and mutated daughter cells) and Homoplasmic (only mutated or only normal daughter cells) - Higher rate of mutations then Euk (no check ups)
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Replicative Segregation or Cytoplasmic Segragation |
- Heteroplasmic: combination of normal and mutated daughter cells (Variable expressivity on diseases due to Heteroplasmic: everyone shows traits @ different levels; and individual with disease will have more mutated mitochondrial cells on it then a normal individual not showing the disease)
- Homoplasmic: only mutated or only normal daughter cells |
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Replication |
- Synthesis of DNA molecule using DNA template (doesn’t occur de novo) - semi conservative: each strand serves as a template (model) to make another complementary strand - Why? – cells are going to divide - When? – prokaryotes = during cell division, eukaryotes = prior to cell division (S phase) - Where? – prokaryotes = in cytosol, eukaryotes = nucleus, mitochondria, chloroplast - Needed? – DNA template; A,T,C,G nucleotides (nucleotide triphosphate); primase (prokaryotes); DNA polymerase with primase activity (eukaryotes); single-stranded binding proteins; RNA nucleotides; DNA polymerases; ligase; helicase; topoisomerases; initiation and elongation factors; licensing factor (eukaryotes) - Δ G = positive (+) - Requires energy, source = triphosphate cleavage (break phosphoanhydrous bonds) - DNA replication is semi conservative, each daughter DNA consists of one old and one new strand
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Types of DNA replication |
Depends where DNA is:
- Theta = circular DNAs of prokaryotes (unidirectional or bidirectional)no broken sugar Phosphate - Rolling circle = conjugation plasmids; in some viruses and in the F factor of E.coli, one strand to each bacteria, cut sugar phosphate - Eukaryotic linear = eukaryotic chromosomes (bidirectional), don't break sugar phosphate - Mitochondria = unidirectional from 2 origins, don't break sugar phosphate
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Replication: Initiation |
- Proteins bind to DNA - Binding is not random, occurs at specific sites called “origin of replication” sites (ORI) - ORI sites are made of A and T (less H bonds) - In eukaryotes but not prokaryotes, eukaryotic process must be licensed - Helicase binds to DNA and breaks H bonds between the bases - Single stranded binding protein = stabilize the replication bubble; prevent the two DNA strands from joining together - Licensing Factor --- Minichromosome Maintenance (MCM) --- Initiates replication simultaneously at all ORI sites
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Replication: Initiation DNA Polymerase |
- DNA Polymerase Only adds nucleotides to 3’ – OH end of another nucleotide (all DNA synthesized n 5’ -> 3’ direction) - Cannot bind to single stranded DNA; dsDNA ONLY - Prokaryotes have 5 (DNA polymerase III elongates DNA) - Eukaryotes: --- Alpha – primase activity --- Delta – synthesizes lagging strand --- Epsilon – synthesizes leading strand - When primer removed from the end, DNA poly cannot bind to single strand - Primase or DNA Polymerase with Primase Activity add short primer strands (forms primer)
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Primer |
Short sequence of RNA nucleotides, provides double stranded platform for DNA polymerase to attach |
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Leading Strand |
- Synthesized continuously in the direction of helicase movement (5’ -> 3’) - Made in one continuous motion |
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Lagging Strand |
- Synthesized discontinuously in chunks called Okazaki fragments (3’ -> 5’) in the direction opposite to helicase movement - Ligase forms phosphodiester linkages between Okazaki fragments - Topoisomerase = relieves torsional stress of DNA caused by separation of strands by helicase - Phosphodiester bonds made by = DNA polymerase, ligase, primase
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Telomerase |
- Every replication means a shortening of the chromosome, telomeres are shortened instead because they are nonfunctional - In germ cells undergoing meiosis, a gene (silent in somatic cells) is turned on; gene codes for telomerase (protein-RNA complex) - A cell that becomes cancerous activates its telomerase gene
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Replication is Very Faithful |
- High nucleotide selection - DNA proofreading ability of DNA polymerase (3’ —> 5’ exonuclease activity) - Error rate = 1/ 109 - Repair mechanisms for mistakes
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Transcription |
- Synthesis of RNA molecule from a DNA template - DNA is transcribed into a RNA molecule (resultant RNA = transcript or RNA transcript) - Happens in the nucleus, mitochondria, and chloroplast - 3 steps: initiation, elongation, termination - NEEDED = DNA template, RNA nucleotide (nucleoside triphosphates – A, U, G, C), RNA polymerase, transcription factors, enhancers, topoisomerases - Not needed -- Helicase = one of basal transcription factors bound to RNA poly has helicase activity --- Ligase = no lagging strand, made continuously --- Primase = RNA poly can bind to ssDNA ---- SSBP = single strand of DNA not destabilized to the degree observed in replication
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Gene |
- Sequence of DNA that codes for an RNA molecule
- Prokaryotes = intronless, gene is all coding
- Eukaryotes = have coding exons, and noncoding introns
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Promoter |
- At +1 ; - negative side = upstream - positive side = downstream - Consists of series of bases (typically rich in A and T) - Not all of the promoter sequence is needed - Consensus sequence = important region - In Eukaryotes, 3 promoter types: --- TATA box (most common) --- CpG “island” (constitutive genes) --- Other variable types (initiator) |
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RNA polymerase |
- Prokaryotes = RNA poly I - Eukaryotes = RNA poly I, II (mRNA), III - Can attach to ssDNA - Can ONLY add nucleotide to 3’ – OH end (5’—> 3’ using 3’ to 5’ DNA) - With aid of basal transcription factors, can unwind DNA (break H bonds between bases)
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Initiation |
- RNA polymerase attaches to promoter that has basal transcription factors attached to it |
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Elongation |
- Goes downstream - Template/ sense strand (noncoding) = 3’ to 5’ (where nascent RNA is formed 5’ —> 3’) - Nontemplate strand (coding) = exists as 5’ to 3’
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Post- Transcriptional Modifications in Eukaryotes |
Pre-mature mRNA undergoes 3 modifications - 5’ capping with methylguanine - 3’ polyadenylation - Intron removal and exon splicing - After ready is called mature mRNA and is ready for translation |
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5’ Capping |
- 5’ Capping Methylguanine is added to the 5’ nucleotide in a rare 5’—> 5’ linkage - Protects the 5’ end from degradation from exonucleases (by changing the shape of the end) - Helps in binding to ribosome |
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3’ Polyadenylation |
- Addition of multiple sequence of A nucleotides to 3’ end - Protects 3’ end from exonucleases - Helps in translocation of mRNA to the cytosol
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Intron Removal and Exon Splicing |
- For nuclear mRNA introns, removal is done by a snRNA-protein complex called a spliceosome - Branchpoint = a - Forms lariat introns
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Alternative Splicing |
- Multiple mRNAs can be made from the same gene
- Splicing of different exons
- Isoforms = different proteins made from the same gene except they differ due to alternative splicing
Ex: fibroblast in fibronectin; and hepatocyte in fibronectin
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RNA editing |
RNA nucleotides are altered after transcription |
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Translation |
- Synthesis of polypeptides using a mRNA template - Where = on ribosomes in cytosol, mitochondria, chloroplasts (eukaryotes); prokaryotes = in cytosol - Why = form proteins which are the molecular machines that make life possible - When = need regulated and/or constitutive proteins - Needed = mRNA (template) [blueprint], ribosome [constructive site], amino acids (building blocks of polypeptides) [bricks], amino-acyl tRNA synthetase (add a.a. to tRNA) [trucks], tRNAs (bring a.a to ribosome) [loaders], GTP (and some ATP) (source of energy); initiation factors, elongation factors, and termination factors (all factors are proteins) - Polypeptide [building]
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Ribosomes |
- Non-membrane bound organelles found in all cell types - The site of protein synthesis (constructive site) - Consist of rRNA and proteins - Functional ribosomes consist of a united large and small subunit - Prokaryotes = 70S —> 50S and 30S - Eukaryotes = 80S —> 60S and 40S - S value dependent on density and shape |
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Genetic Code |
- Sequence of nucleotides in DNA, read 3 at a time (codon), that specifies the position of an amino acid in a polypeptide - Co-linearity --- DNA = 5’ —> 3’ --- mRNA = 5’ —> 3’ --- polypeptide = N —> C - triplet code - 64 codons - 61 codons = sense codons (specify amino acid) – has 1 start codon (methionine - AUG in EUK; Formethionine in Prok) - 3 stop or nonsense codons - Is specific - Is redundant (degenerate), same aa changes on 3rd bp only - redundancy occurs because of wooble - Nonoverlapping - Continuous - Nearly universal - Appear in the mRNA as 5’ —> 3’
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Wobble |
- Relaxation of the base pairing rules between the 1st base of the anticodon tRNA and the 3rd base of the mRNA
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tRNA |
- Acceptor stream: 3' end has a ACC anti codon that has a OH' group that will attach to the carbonyl group of the coming aa, making a high energy ester bond and an ATP |
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Translation Initiation |
- mRNA interacts with small subunit of ribosome - In Prokaryotes: Shine Dolgano is required for binding - Large subunit binds to mRNA - First aa goes to P site, second and on goes to A site |
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Translation Elongation |
- Once complex is made: " Peptidyl transferase activity" of the ribosome (catalytic) makes peptides bonds among a.a. _ Ribosome moves on mRNA stand downstream 5'--> 3' (Translocation) |
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Translation Termination |
- when reaches stop codon, releasing factors will stop translation and everything (complex) disabled and released |
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Polypeptide Post-Translation Modifications |
- Disulfide bridges addition (PPI: found in lumen of RER in Euk.) - Addition of chemocal groups to the N-terminus - Glycolysation (in Golgi) - Acetylation (most common) - Phosphorylation (by Kinases) - Methylation - Hydroxylation - Carboxylation - Cleaverage of amino acids - Addition of a.a. - Shape modifications by chaperones or chaperonins
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Genome |
Total number of genes (genetic make up) |
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Transcriptone |
Total number of RNA |
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Proteome |
Total number of proteins |
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Proteome Complexity |
- Millions of proteins - Diversity: modifications give different results - Post Modifications - Alternative splicing - RNA editing (RNA nucleotides are altered after transcription; Guide RNA binds to transcript and GRna causes addition or deletion of bases)
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