Nt1310 Unit 1 Exercise 1
Chapter 12
Cyclins and cyclin-dependent kinases are regulatory proteins that assist in the cell cycle. Particular protein kinases give the go-ahead signals at G1 and G2 checkpoints. These protein kinases are present at a constant concentration in the cell but are inactive unless in the presence of cyclin, these are cyclin dependent kinases. The activity of a cdk rises and falls with the concentration of cyclin. Cyclin levels rise during the S and G2 phases then fall abruptly in the M phase.
MPF – maturation-programming factor – cyclin cdk complex that triggers a cells passage past the G2 checkpoint into the M phase (m-phase promoting factor). May assist in the fragmentation of the nuclear envelope during prometaphase. Helps to switch itself …show more content…
off by initiating a process that leads to the destruction of its own cyclin.
Platelet-derived growth factor, stimulates human fibroblast division in culture and in an animal. PDGF is released when injury occurs stimulating fibroblast growth and healing the wound.
Cancer cells – are cells that do not display density-dependent inhibition, they do not stop proliferating even when there is no more space, nor do the display anchorage dependence, they do not need to be attached to a substratum to divide, they also often create their own growth factors, and often don’t even need a growth factor to divide, and normal mitotic checkpoints are not present in a cancer cell, therefore cancer cells may have an abnormal cell cycle control system.
Normal cell becomes cancerous by ‘transformation,’ cancer cells that are not destroyed by the immune system become tumors. Tumors can be either benign or malignant. Malignant tumors often spread and metastasize and can cause serious problems whereas benign tumors can often be removed with no serious complications. Often cancer cells have lost the ability to fix DNA when it becomes damaged which is why localized radiation effects cancer cells more so than it effects normal cells.
Mitosis:
Cytokinesis: Plant Cells – golgi vesicles move along microtubules to the middle of the cell, where the coalesce, producing a cell plate, which eventually fuses with the cell wall and splits the cell in two Animal Cells – A cleavage furrow forms. On the cytoplasmic side of this cleavage furrow there is a contractile ring of actin filaments associated with molecules of the protein myosin. These two molecules interact causing the cleavage furrow to contract and act as a drawstring until the cell eventually splits in two.
I DON’T HAVE CHAPTER 13
Chapter 14
Punnett Square Calculations:
Multiplication Rule – probability two or more independent events will occur together is the product of their individual probabilities.
Probability of a monohybrid cross can be determined this way. Each gamete has a ½ chance of getting the dominant allele and a ½ chance of getting the recessive allele. Example: ½ R ½ r
½ R
¼ RR
¼ Rr
½ r
¼ Rr
¼ rr 1:2:1 genotypic, 3:1 phenotypic
In calculating the chances for various genotypes, each character is considered separately, and the individual probabilities are multiplied. Such as in a dihybrid or monohybrid cross.
Addition Rule - probability that any one of two or more mutually exclusive events will occur is calculated by adding their individual probabilities.
This can be used to find the probability that an F2 plant from a monohybrid cross will be heterozygous rather than homozygous. E.g. use the probabilities from using multiplication and add them to determine the probability that an F2 plant will be heterozygous.
These rules are used to predict the outcome of crosses with multiple characters. ** A dihybrid, or other multi-character, cross is equivalent to two or more independent monohybrid crosses occurring simultaneously.
Gregor Mendel Pea Plants, Why?
Many varieties with distinct heritable characters or traits (e.g. flower color)
Mating easy to control; Can cross pollinate (fertilization between different plants)
Each flower has sperm producing, stamen, and egg producing, carpel, organs
Short generation time
Large number of offspring from each mating
Tracked only traits that had two distinct alternate forms, and always started with only true breeding plants (Homozygous) produce offspring identical to them when they self-pollinate
Used very large sample sizes, allowed him to get the results he did.
P Generation cross results in the F1 generation F1 generation cross results in the F2 generation ** continuing to F2 allowed
Mendel to see the inheritance patterns he saw.
Results of Mendel’s Experiments:
P generation cross – PP x pp (true breeding)
F1 result – all Pp (express dominant phenotype)
F1 cross – Pp x Pp (heterozygous)
F2 result, phenotypic – 3:1, purple : white
F2 result, genotypic – 1:2:1, PP:Pp:pp
Mendelian Model of Genetics: (discovered from the experiment above)
1) Alleles – alternate versions of genes that account for the variations in inherited characters. Each at a specific locus on a chromosome. Alleles at corresponding loci on a pair of homologous chromosomes.
2) One Allele from each parent – inherits one allele from each parent, can be homozygous (same, like P-generation of true breeding type) or heterozygous (different like F1 hybrid generation).
3) If heterozygous the Dominant allele determines phenotype and the recessive have no noticeable affect on the phenotype.
4) Law of Segregation – two alleles for a heritable character separate during gamete formation and end up in different gametes. (Each gamete gets one allele)
Test Cross to determine genotype of unknown trait that displays dominant phenotype. (Could be homozygous or heterozygous). Breed unknown with a homozygous recessive individual – if homozygous dominant all will be heterozygous dominant and only display dominant phenotype. If heterozygous – recessive phenotype will appear in F1generation (½, ½).
Monohybrid cross – cross between two individuals heterozygous for one trait
Dihybrid cross – cross between two individuals heterozygous for two traits. This can also determine whether two characters are linked or are transmitted independently
^^ These are both generally F1 crosses from a P gen that is true breeding.
Law of Independent assortment – each pair of alleles segregates independently of each other pair of alleles during gamete formation, though this only applies to pairs of alleles on nonhomologous chromosomes or far apart on the same chromosome, (discovered by following two traits pea seed shape and color). However, if gene loci are close enough together they will typically be inherited together (in crossing over they tend to stay together).
More Complex Patterns of Inheritance
Basic principles of segregation and independent assortment still apply, however there are more complex means of inheritance that what Mendel observed. Deviance from Mendelian Patterns
When alleles don’t display complete dominance or complete recessiveness
Complete dominance – phenotypes of the heterozygote and the dominant heterozygote are identical. (e.g. PP and Pp show the same phenotype, both purple)
Incomplete dominance – the phenotype of F1 hybrids expressed is an intermediate between the phenotypes of the parental varieties. (e.g. Red Snapdragons CRCR x White Snapdragons CWCW yields an F1 generation of Pink Snapdragons – CRCW)
Codominance – two dominant alleles affect the phenotype in separate, distinguishable ways. (e.g. ABO blood typing: A, or AO, B, or BO, AB, OO)
Dominance/Recessiveness of alleles depends upon the level at which the phenotype is examined:
e.g. Tay Sachs Disease
Organismal level, the allele is recessive
Biochemical level (enzyme activity level), the allele is incompletely dominant
Molecular level, the alleles are codominant
Dominant alleles are not always more common in populations than recessive alleles (e.g. polydactyly is dominant but affects 1/400 in US)
When a gene has more than two alleles
Most genes exist in populations in more than two allelic forms.
e.g. four phenotypes of ABO blood typing, determined by three alleles for an enzyme, I that attaches A or B carbohydrates to blood cells. Alleles: IA, IB, i
When a gene produces multiple phenotypes
Pleiotropy – a gene that has multiple phenotypic effects. (One gene affects more than one characteristic in an organism)
e.g. various symptoms of cystic fibrosis, sickle-cell disease, and Marfan syndrome.
Extending Mendelian Genetics for Two or More Genes
Epistasis - when a gene at one locus alters the phenotypic expression of a gene at a second locus.
e.g. Labrador retrievers coat color
One gene determines pigment color (B – black, b-brown), the other gene determines if the pigment is deposited in the hair (E - color, e – no color)
Polygenic Inheritance – an additive effect of two or more genes in a single phenotype. Marked by quantitative characters, which are characters that vary in the population along a continuum.
e.g.
Skin color in humans, many genes determine the skin color and offspring is expected to express an intermediate phenotype
When products of many genes influence a trait, individuals of a population show a range of continuous variation.
Environmental Impact on Phenotype The environment has an impact on the phenotype of an individual.
e.g. tanning makes skin darker, exercise alters build, nutrition influences height.
Genotype is associated with a range of phenotypic possibilities due to environmental influences.
Norm of reaction – the phenotypic range of a genotype influenced by the environment. (generally the broadest range is seen for polygenic characters)
e.g. hydrangea flowers of the same genotype can range from blue-violet to pink depending on the acidity and aluminum content of the soil.
e.g. temperature and rabbit fur color. Coldness will darken the fur.
Multifactorial – characters where genetic and environmental factors collectively influence the phenotype.
** An organisms phenotype includes its physical appearance, internal anatomy, physiology and behavior, and reflects its overall genotype and unique environmental history.
Humans and Mendelian Patterns of Inheritance
Pedigree
A family tree that describes the interrelationships of parents and children across generations (inheritance patterns of particular traits can be traced and described using pedigrees)
Understanding pedigrees:
Mendelian ratios (3:1) are rarely observed because the sample size is too small
Pedigrees are used to show different inheritance patterns this includes:
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Codominance
Incomplete dominance
Examples are shown below:
Pedigrees can be used to make predictions about future offspring. We can use multiplication and addition rules to predict the probability of specific phenotypes in a pedigree.
Recessively Inherited Disorders
A recessively inherited disorder must be homozygous for the recessive allele for the individual to be affected by the disorder.
People who are heterozygous and do not phenotypically express the disorder are said to be carriers of the disease.
e.g. Albinism, it’s a recessive disorder that is only expressed in homozygous recessive individuals.
Dominantly Inherited Disorders These disorders are very rare and are caused by dominant alleles.
Achondroplasia is a form of dwarfism caused by a rare dominant allele.
Genetic Testing and Counseling
Genetic counselors provide information to prospective parents about their family history for a specific disease. They help determine the odds that the child will be affected by the disorder.
Tests are available to test for many genetic disorders and can help identify carriers and help to predict probability of offspring more accurately.
Fetal Testing
Amniocentesis – amniotic fluid around fetus is removed through a needle through the lower abdomen and is tested.
Chronic villus sampling (CVS) a sample of the placenta is removed and tested.
Chapter 15
Thomas Hunt Morgan
Showed first solid evidence associating a specific gene with a specific chromosome. Did experiments with fruit flies that showed convincing evidence that chromosomes are the location of Mendel’s heritable factors, though he did not initially support them.
Won Nobel Prize in 1933
Why Fruit Flies?
They produce many offspring
A generation can be bred every two weeks
They only have four pairs of chromosomes
About the Experiment:
Wild types were observed and described as normal phenotypes that were common in the fly populations. Alternative traits were called mutant phenotypes. (White eyes – “w”, red eyes [wild-type] – “w+”
Results
Mated white-eyed males (mutant), with wild-type (red-eyed) females.
F1 generation: all red eyes.
F2 generation: 3:1, red:white ratio, but only males had white eyes.
Morgan determined that the white-eyed mutant allele must be located on the X chromosome.
Sex-Linked Inheritance XX – female; Ovum only contain an X chromosome XY – male, SRY gene on the Y chromosome codes for a protein that directs development of male anatomical features. Sperm can contain an X or Y chromosome.
Sex-linked gene – a gene located on either sex chromosome. (Y-linked, very few, and X-linked).
X chromosomes have genes for many characters unrelated to sex, where Y chromosomes mainly has genes related to sex determination.
X-Linked Inheritance For a recessive x-linked trait to be expressed:
A female must be homozygous recessive for the allele
A male only needs one copy of the allele (hemizygous)
** X-linked recessive are much more common in males than females.
Example: color blindness, Duchenne muscular dystrophy, hemophilia
Barr Body - In mammalian females the one X-chromosome is randomly inactivated during embryonic development.
If she is heterozygous for a particular trait she will be mosaic for that character. (Half will express one allele, the other half will express the alternate allele)
Linked Genes Genes that are located on the same chromosome and tend to be inherited together (Each chromosome has hundreds, or thousands of genes, except y chromosome)
Morgan did experiments with fruit flies to see how linkage affects inheritance of two characters. He crossed flies that differed in traits of body color and wing size.
Results
P generation: wild type, gray body with normal wings x double mutant, black body with vestigial wings. b+ b+ vg+ vg+ x b b vg vg
F1 result: b+ b vg+ vg and b b vg vg. Wild type & double mutant
F1 dihybrid cross: heterozygous wild-type female x homozygous double mutant male b+ b vg+ vg x b b vg vg
F2 result: b+ b vg+ vg, b b vg vg, b+ b vg vg, b b vg+ vg Wild type, black vestigial, gray-vestigial, black-normal 965 : 944 : 206 : 185
Conclusion: because most offspring maintained the parental phenotype, it was concluded that genes for body color and wing size are genetically linked on the same chromosome. However, the presence of nonparental phenotypes is indicative of a mechanism that breaks the linkage between specific alleles of genes on the same chromosome (crossing over).
Genetic Recombination – the production of offspring with combinations of traits that differ from those found in either parent.
Recombination of unlinked genes is merely the Independent Assortment of Chromosomes
Offspring with parental phenotypes are called parental types
Offspring with nonparental phenotypes are called recombinant types or recombinants.
A 50% frequency of recombination is observed for any two genes on different chromosomes.
Physical basis of recombination is due to the random orientation of homologous chromosomes at metaphase I of meiosis, which leads to the independent assortment of unlinked genes.
Crossing Over during meiosis I is the mechanism that causes the linkage between linked genes to be incomplete, it allows some recombinant phenotypes to be observed. The recombination frequency of Morgan’s fruit fly dihybrid cross was 17%
Alfred Sturtevant and Genetic Mapping
Created a genetic map that showed an ordered list of genetic loci along a particular chromosome
Predicted the farther apart two genes are, the higher the probability that a crossover will occur between them, and therefore the higher the recombination frequency.
Linkage map – a genetic map based on recombination frequencies
Distances between genes can be expressed as map units and represent a 1% recombination frequency. (indicate relative distance and order, not precise locations of genes)
Cytogenic maps - are maps that actually indicate the positions of genes with respect to chromosomal features. (This is done using methods like chromosomal banding)
Alterations of Chromosomes and Genetic Disorders Nondisjunction – the members of a pair of homologous chromosomes do not move apart properly in meiosis I, or when sister chromatids fail to separate during meiosis II. [one gamete receives two copies of that chromosome, whereas another gamete will not receive any copies of that chromosome]
This causes abnormalities in chromosome number. In mammals and humans these often lead to miscarriages, whereas plants are much more tolerant to genetic changes.
Aneuploidy
Abnormal chromosome number, results from the fertilization of a gametes in which nondisjunction occurred.
Monosomic zygote has only one copy of a particular chromosome
Trisomic zygote has three copies of a particular chromosome.
Polyploidy
A condition where an organism has more than two complete sets of chromosomes
Triploidy (3n) is three sets of chromosomes
Tetraploidy (4n) is four sets of chromosomes
More common in plants than animals, display a more normal phenotype than aneuploids.
Alterations of Chromosome Structure
Breakage of a chromosome can lead to four types of changes in chromosome structure
Deletion removes a chromosomal segment
Duplication repeats a segment
Inversion reverses orientation of a segment within a chromosome
Translocation moves a segment from one chromosome to another
Alterations of chromosome number and structure result in some serious disorders if the alterations are not fatal. These disorders have a set of symptoms characteristic of the type of aneuploidy.
Genetic Disorders
Downs Syndrome (Trisomy 21)
Three copies of chromosome 21
1/700 children born in US
Characterized by distinct facial features, short stature, heart defects, developmental delays, often under-developed and sterile.
Trisomy 18
1/7000 births increased risk of birth defects, especially the heart.
Trisomy 13
1/10000 births increased risk of birth defects, including heart, eyes, and ears.
Aneuploidy of Sex Chromosomes (nondisjunction of sex chromosomes)
Kleinfelter syndrome XXY
1/500-1000 births male sex organs, but abnormally small testes and man is sterile
Some breast enlargement and other female body characteristics are common
Subnormal intelligence
Turner syndrome X0 (monosomy X)
1/2500 female births
Only known viable human monosomy
Do not develop secondary sex characteristics, sterile
Can undergo hormone replacement therapy and will develop secondary sex characteristics.
Normal intelligence
XYY Males (Diplo Y, Jacob’s Syndrome)
1/1000 male births
No definable symptoms, but may have certain traits:
Taller than average, more acne,
XXX Females (Trisomy X)
1/1000 female births
Few symptoms but:
May be taller than average, slightly lower IQ’s, prone to learning disabilities, introverted, clumsy, awkward.
Disorders Caused by Structurally Altered Chromosomes
Cri du chat (cry of the cat) specific deletion in chromosome 5
Mentally retarded, cat-like cry
Usually die in infancy or early childhood
Chronic Myelogenous Leukemia (CML)
Caused by a reciprocal translocation during mitosis of cells that will become white blood cells.
The exchange of a large portion of chromosome 22 and a small fragment of chromosome 9, this creates a distinct shortened chromosome 22 known as the Philadelphia chromosome.
Creates BCR-abl fusion protein, a protein kinase involved in mitotic signaling
Cells constantly stimulated to divide and soon overwhelm normal blood components
*** Gleevac – a drug that targets this aberrant protein kinase, blocks ATP binding on kinase and prevents activation; Highly specific for ATP binding pocked on fusion protein. 90% of patients treated show complete remission.
Exceptions to Mendelian Genetics There are two normal exceptions. In both cases, the sex of the parent contributing the allele is a factor in the pattern of inheritance.
Genes located in the nucleus
Genomic imprinting
Variation in the phenotype depending on whether the allele is inherited from the mother or the father.
Most imprinted genes are on autosomal chromosomes and are critical for embryonic development
Occurs during gamete formation – results in the silencing of a particular allele of certain genes.
Believed to be the result of methylation of cysteine nucleotides
A zygote will only express one allele of an imprinted gene, which is inherited from either the male or the female parent.
Imprinting is “erased” in each generation and are newly imprinted in gametes that are formed.
A gene imprinted for the maternal allele expression is always imprinted this way.
Genes located outside the nucleus
Cytoplasmic Genes, or extranuclear genes, are found in organelles in the cytoplasm
Mitochondria, chloroplasts, and other plant plastids carry small circular DNA molecules.
Extranuclear genes are inherited maternally because the zygote’s cytoplasm comes from the egg.
Evidence of this came from studies on the inheritances of yellow or white patches on leaves of an otherwise green plant.
Chapter 16 Important People In Biology
Frederick Griffith – Used two strains of the streptococcus pneumoniae bacteria, one pathogenic, the S cells, and nonpathogenic, the R cells. He then injected mice with living R cells (control), living S cells (control), Heat-Killed S cells, and a mixture of Heat-Killed S cells and living R cells. The result was that the Heat-Killed S cells alone were not pathogenic and the mouse lived, and the Mixture of Heat-Killed S cells and Living R cells was pathogenic and the mouse died (There was evidence of living, replicating S cells in the blood of these mice), and therefore he concluded that the living R bacteria had been transformed into the pathogenic S bacteria by an unknown, heritable substance that allowed the R cells to make capsules.
Oswald Avery/Maclyn McCarty/Colin MacLeod – Focused on three main elements to be the unknown heritable factor from Griffith’s experiment, DNA, RNA, and proteins. Avery broke open heat-killed pathogenic bacterial cells and treated each of the three samples with an agent that inactivated one type of molecule. He discovered that only when DNA was allowed to remain active did the sample have a transforming ability. Therefore he claimed that DNA was the transforming agent but so little was known about DNA that nobody really took him seriously. (1944)
Hershey/Chase – used T2 bacteriophages one group marked with radioactive sulfur (proteins) and one marked with radioactive phosphorus (DNA) and allowed the bacteriophages to affect bacteria. The mixtures were then agitated separately to separate phage parts from outside of the bacteria, these mixtures were then centrifuged so that bacteria formed a pellet at the bottom of the test tube and radioactive phosphorous was detected in the pellet, and therefore in the bacteria cells. This allowed Hershey and Chase to conclude that viral DNA entered bacterial cells, but proteins did not, and therefore DNA is the genetic material of phage T2. (1952)
Chargaff – in 1950 reported that he found that the base composition of DNA varies from one species to another. Meaning that humans have a different base pair composition than a dog would etc. He also found that the amount of adenine = thymine and the amount of guanine = cytosine, for example in humans, A= 30.3%, T= 30.3%, G = 19.5 %, and C = 19.9%.
Watson/Crick – used Rosalind Franklin’s X-ray crystallography to predict the double helix formation of DNA, they lined the sugar-phosphate backbones in an antiparallel manner (5’3’, 3’5’). They used the X-ray measurements to discover that in DNA a pyrimidine bonds with a purine, and that A bonds with only T and C bonds with only G and vice versa. Their model also predicts a semiconservative model of replication.
Matthew Meselson – cultured E. coli in medium with a heavier nitrogen isotope then transferred the bacteria into a medium with a lighter nitrogen isotope. A sample was taken and centrifuged after one DNA replication and then again after a second DNA replication. The centrifuged results showed a mid-density radioactive pellet, the second showed a mid density radioactive pellet and a lighter density radioactive pellet this information is consistent with the predicted semiconservative replication model of DNA.
DNA Replication Basic Terms:
Origin of Replication – where the replication of a DNA molecule begins. They have a specific sequence of nucleotides indicating a start of replication. The two strands are opened up and a replication “bubble” forms
Replication Fork – a Y- shaped region where parental DNA strands are being unwound.
Helicase – enzymes that untwist the double helix that the replication fork , separating the two parental strands making them available as template strands.
Single Strand Binding Proteins – bind to unpaired DNA strands after parental strands have been separated to stabilize the unpaired DNA and prevent it from re-pairing.
Topoisomerase – helps to relieve stress that occurs ahead of the replication fork as DNA is unwound. It does this by breaking, swiveling, and rejoining DNA strands.
Primer – a short stretch of RNA that is used to prime a DNA strand for DNA replication as the proteins used for DNA replication cannot initiate synthesis of a polynucleotide on their own.
Primase – the enzyme that synthesizes RNA primers. Primase starts the complementary RNA primer from a single nucleotide and then adds RNA nucleotides one at a time using the parental strand as a template. A completed primer is generally 5-10 nucleotides long.
* New DNA can only be added to the 3’ end of the primer.
DNA Polymerase – catalyzes the synthesis of a new DNA strand by adding nucleotides to an already existing chain (the primer)
Leading Strand – because nucleotides can only be added to the 3’ end of a DNA chain, and DNA is antiparallel, the leading strand is the strand that is added continuously in the 5’3’ direction (on the parental DNA going in the 3’5’ direction). Towards the replication fork
Lagging Strand – the strand of DNA forming whose template during replication goes in the 5’3’ and therefore DNA cannot be added continuously in on the 3’, it has to be added away from the replication fork and is added in fragments known as Okazaki fragments.
* DNA polymerase I replaces RNA primer strands in the 5’3’ direction, resulting in a continuous DNA strand.
DNA ligase – joins the phosphate-sugar backbones of all the Okazaki fragments.
Mismatch repair – a method of removing and replacing incorrectly paired nucleotides that resulted from a replication error one type can be seen below:
Nuclease Excision Repair
Teams of enzymes detect and repair damaged DNA (such as thymine dimers etc. can be caused by UV radiation) which distorts the DNA molecule
A nuclease enzyme cuts the damaged DNA strand at two point, and the damaged section is removed
Repair synthesis by a DNA polymerase fills in the missing nucleotides
DNA ligase seals the free end of the new DNA to the old DNA, making the strand complete.
Nuclease – DNA cutting enzyme, that helps to excise damaged DNA bases.
* The 5’ end of the final RNA primer on the lagging strand can never be replaced with DNA because you cannot add to the 5’ end of DNA therefore DNA shortens with each replication this is why we need telomeres
Telomeres – special nucleotide sequences at the end of DNA that helps to protect the degradation of DNA. Do not contain genes but rather many repetitions of one short nucleotide sequence. Degradation of telomeres is said to be associated with aging.
Telomerase – enzyme that catalyzes the lengthening of telomeres in eukaryotic germ cells, which restores the DNA length compensating for the shortening that occurs during replication.
DNA Packaging and Chromatin
Nucleoid – the dense region in a bacteria cell that contains DNA
DNA is condensed into chromosomes by wrapping around histones and forming nucleosomes (beads on a string) these coil or fold forming a 30 nm chromatin fiber, this fiber then forms looped domains and forms into a 300 nm fiber. These then coil and fold into the distinct chromosome shape. Chromatin – complex of DNA and proteins (histones). Heterochromatin – interphase-type chromatin that is tightly packed Euchromatin – loosely packed chromatin
Cyclins and cyclin-dependent kinases are regulatory proteins that assist in the cell cycle. Particular protein kinases give the go-ahead signals at G1 and G2 checkpoints. These protein kinases are present at a constant concentration in the cell but are inactive unless in the presence of cyclin, these are cyclin dependent kinases. The activity of a cdk rises and falls with the concentration of cyclin. Cyclin levels rise during the S and G2 phases then fall abruptly in the M phase.
MPF – maturation-programming factor – cyclin cdk complex that triggers a cells passage past the G2 checkpoint into the M phase (m-phase promoting factor). May assist in the fragmentation of the nuclear envelope during prometaphase. Helps to switch itself …show more content…
off by initiating a process that leads to the destruction of its own cyclin.
Platelet-derived growth factor, stimulates human fibroblast division in culture and in an animal. PDGF is released when injury occurs stimulating fibroblast growth and healing the wound.
Cancer cells – are cells that do not display density-dependent inhibition, they do not stop proliferating even when there is no more space, nor do the display anchorage dependence, they do not need to be attached to a substratum to divide, they also often create their own growth factors, and often don’t even need a growth factor to divide, and normal mitotic checkpoints are not present in a cancer cell, therefore cancer cells may have an abnormal cell cycle control system.
Normal cell becomes cancerous by ‘transformation,’ cancer cells that are not destroyed by the immune system become tumors. Tumors can be either benign or malignant. Malignant tumors often spread and metastasize and can cause serious problems whereas benign tumors can often be removed with no serious complications. Often cancer cells have lost the ability to fix DNA when it becomes damaged which is why localized radiation effects cancer cells more so than it effects normal cells.
Mitosis:
Cytokinesis: Plant Cells – golgi vesicles move along microtubules to the middle of the cell, where the coalesce, producing a cell plate, which eventually fuses with the cell wall and splits the cell in two Animal Cells – A cleavage furrow forms. On the cytoplasmic side of this cleavage furrow there is a contractile ring of actin filaments associated with molecules of the protein myosin. These two molecules interact causing the cleavage furrow to contract and act as a drawstring until the cell eventually splits in two.
I DON’T HAVE CHAPTER 13
Chapter 14
Punnett Square Calculations:
Multiplication Rule – probability two or more independent events will occur together is the product of their individual probabilities.
Probability of a monohybrid cross can be determined this way. Each gamete has a ½ chance of getting the dominant allele and a ½ chance of getting the recessive allele. Example: ½ R ½ r
½ R
¼ RR
¼ Rr
½ r
¼ Rr
¼ rr 1:2:1 genotypic, 3:1 phenotypic
In calculating the chances for various genotypes, each character is considered separately, and the individual probabilities are multiplied. Such as in a dihybrid or monohybrid cross.
Addition Rule - probability that any one of two or more mutually exclusive events will occur is calculated by adding their individual probabilities.
This can be used to find the probability that an F2 plant from a monohybrid cross will be heterozygous rather than homozygous. E.g. use the probabilities from using multiplication and add them to determine the probability that an F2 plant will be heterozygous.
These rules are used to predict the outcome of crosses with multiple characters. ** A dihybrid, or other multi-character, cross is equivalent to two or more independent monohybrid crosses occurring simultaneously.
Gregor Mendel Pea Plants, Why?
Many varieties with distinct heritable characters or traits (e.g. flower color)
Mating easy to control; Can cross pollinate (fertilization between different plants)
Each flower has sperm producing, stamen, and egg producing, carpel, organs
Short generation time
Large number of offspring from each mating
Tracked only traits that had two distinct alternate forms, and always started with only true breeding plants (Homozygous) produce offspring identical to them when they self-pollinate
Used very large sample sizes, allowed him to get the results he did.
P Generation cross results in the F1 generation F1 generation cross results in the F2 generation ** continuing to F2 allowed
Mendel to see the inheritance patterns he saw.
Results of Mendel’s Experiments:
P generation cross – PP x pp (true breeding)
F1 result – all Pp (express dominant phenotype)
F1 cross – Pp x Pp (heterozygous)
F2 result, phenotypic – 3:1, purple : white
F2 result, genotypic – 1:2:1, PP:Pp:pp
Mendelian Model of Genetics: (discovered from the experiment above)
1) Alleles – alternate versions of genes that account for the variations in inherited characters. Each at a specific locus on a chromosome. Alleles at corresponding loci on a pair of homologous chromosomes.
2) One Allele from each parent – inherits one allele from each parent, can be homozygous (same, like P-generation of true breeding type) or heterozygous (different like F1 hybrid generation).
3) If heterozygous the Dominant allele determines phenotype and the recessive have no noticeable affect on the phenotype.
4) Law of Segregation – two alleles for a heritable character separate during gamete formation and end up in different gametes. (Each gamete gets one allele)
Test Cross to determine genotype of unknown trait that displays dominant phenotype. (Could be homozygous or heterozygous). Breed unknown with a homozygous recessive individual – if homozygous dominant all will be heterozygous dominant and only display dominant phenotype. If heterozygous – recessive phenotype will appear in F1generation (½, ½).
Monohybrid cross – cross between two individuals heterozygous for one trait
Dihybrid cross – cross between two individuals heterozygous for two traits. This can also determine whether two characters are linked or are transmitted independently
^^ These are both generally F1 crosses from a P gen that is true breeding.
Law of Independent assortment – each pair of alleles segregates independently of each other pair of alleles during gamete formation, though this only applies to pairs of alleles on nonhomologous chromosomes or far apart on the same chromosome, (discovered by following two traits pea seed shape and color). However, if gene loci are close enough together they will typically be inherited together (in crossing over they tend to stay together).
More Complex Patterns of Inheritance
Basic principles of segregation and independent assortment still apply, however there are more complex means of inheritance that what Mendel observed. Deviance from Mendelian Patterns
When alleles don’t display complete dominance or complete recessiveness
Complete dominance – phenotypes of the heterozygote and the dominant heterozygote are identical. (e.g. PP and Pp show the same phenotype, both purple)
Incomplete dominance – the phenotype of F1 hybrids expressed is an intermediate between the phenotypes of the parental varieties. (e.g. Red Snapdragons CRCR x White Snapdragons CWCW yields an F1 generation of Pink Snapdragons – CRCW)
Codominance – two dominant alleles affect the phenotype in separate, distinguishable ways. (e.g. ABO blood typing: A, or AO, B, or BO, AB, OO)
Dominance/Recessiveness of alleles depends upon the level at which the phenotype is examined:
e.g. Tay Sachs Disease
Organismal level, the allele is recessive
Biochemical level (enzyme activity level), the allele is incompletely dominant
Molecular level, the alleles are codominant
Dominant alleles are not always more common in populations than recessive alleles (e.g. polydactyly is dominant but affects 1/400 in US)
When a gene has more than two alleles
Most genes exist in populations in more than two allelic forms.
e.g. four phenotypes of ABO blood typing, determined by three alleles for an enzyme, I that attaches A or B carbohydrates to blood cells. Alleles: IA, IB, i
When a gene produces multiple phenotypes
Pleiotropy – a gene that has multiple phenotypic effects. (One gene affects more than one characteristic in an organism)
e.g. various symptoms of cystic fibrosis, sickle-cell disease, and Marfan syndrome.
Extending Mendelian Genetics for Two or More Genes
Epistasis - when a gene at one locus alters the phenotypic expression of a gene at a second locus.
e.g. Labrador retrievers coat color
One gene determines pigment color (B – black, b-brown), the other gene determines if the pigment is deposited in the hair (E - color, e – no color)
Polygenic Inheritance – an additive effect of two or more genes in a single phenotype. Marked by quantitative characters, which are characters that vary in the population along a continuum.
e.g.
Skin color in humans, many genes determine the skin color and offspring is expected to express an intermediate phenotype
When products of many genes influence a trait, individuals of a population show a range of continuous variation.
Environmental Impact on Phenotype The environment has an impact on the phenotype of an individual.
e.g. tanning makes skin darker, exercise alters build, nutrition influences height.
Genotype is associated with a range of phenotypic possibilities due to environmental influences.
Norm of reaction – the phenotypic range of a genotype influenced by the environment. (generally the broadest range is seen for polygenic characters)
e.g. hydrangea flowers of the same genotype can range from blue-violet to pink depending on the acidity and aluminum content of the soil.
e.g. temperature and rabbit fur color. Coldness will darken the fur.
Multifactorial – characters where genetic and environmental factors collectively influence the phenotype.
** An organisms phenotype includes its physical appearance, internal anatomy, physiology and behavior, and reflects its overall genotype and unique environmental history.
Humans and Mendelian Patterns of Inheritance
Pedigree
A family tree that describes the interrelationships of parents and children across generations (inheritance patterns of particular traits can be traced and described using pedigrees)
Understanding pedigrees:
Mendelian ratios (3:1) are rarely observed because the sample size is too small
Pedigrees are used to show different inheritance patterns this includes:
Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Codominance
Incomplete dominance
Examples are shown below:
Pedigrees can be used to make predictions about future offspring. We can use multiplication and addition rules to predict the probability of specific phenotypes in a pedigree.
Recessively Inherited Disorders
A recessively inherited disorder must be homozygous for the recessive allele for the individual to be affected by the disorder.
People who are heterozygous and do not phenotypically express the disorder are said to be carriers of the disease.
e.g. Albinism, it’s a recessive disorder that is only expressed in homozygous recessive individuals.
Dominantly Inherited Disorders These disorders are very rare and are caused by dominant alleles.
Achondroplasia is a form of dwarfism caused by a rare dominant allele.
Genetic Testing and Counseling
Genetic counselors provide information to prospective parents about their family history for a specific disease. They help determine the odds that the child will be affected by the disorder.
Tests are available to test for many genetic disorders and can help identify carriers and help to predict probability of offspring more accurately.
Fetal Testing
Amniocentesis – amniotic fluid around fetus is removed through a needle through the lower abdomen and is tested.
Chronic villus sampling (CVS) a sample of the placenta is removed and tested.
Chapter 15
Thomas Hunt Morgan
Showed first solid evidence associating a specific gene with a specific chromosome. Did experiments with fruit flies that showed convincing evidence that chromosomes are the location of Mendel’s heritable factors, though he did not initially support them.
Won Nobel Prize in 1933
Why Fruit Flies?
They produce many offspring
A generation can be bred every two weeks
They only have four pairs of chromosomes
About the Experiment:
Wild types were observed and described as normal phenotypes that were common in the fly populations. Alternative traits were called mutant phenotypes. (White eyes – “w”, red eyes [wild-type] – “w+”
Results
Mated white-eyed males (mutant), with wild-type (red-eyed) females.
F1 generation: all red eyes.
F2 generation: 3:1, red:white ratio, but only males had white eyes.
Morgan determined that the white-eyed mutant allele must be located on the X chromosome.
Sex-Linked Inheritance XX – female; Ovum only contain an X chromosome XY – male, SRY gene on the Y chromosome codes for a protein that directs development of male anatomical features. Sperm can contain an X or Y chromosome.
Sex-linked gene – a gene located on either sex chromosome. (Y-linked, very few, and X-linked).
X chromosomes have genes for many characters unrelated to sex, where Y chromosomes mainly has genes related to sex determination.
X-Linked Inheritance For a recessive x-linked trait to be expressed:
A female must be homozygous recessive for the allele
A male only needs one copy of the allele (hemizygous)
** X-linked recessive are much more common in males than females.
Example: color blindness, Duchenne muscular dystrophy, hemophilia
Barr Body - In mammalian females the one X-chromosome is randomly inactivated during embryonic development.
If she is heterozygous for a particular trait she will be mosaic for that character. (Half will express one allele, the other half will express the alternate allele)
Linked Genes Genes that are located on the same chromosome and tend to be inherited together (Each chromosome has hundreds, or thousands of genes, except y chromosome)
Morgan did experiments with fruit flies to see how linkage affects inheritance of two characters. He crossed flies that differed in traits of body color and wing size.
Results
P generation: wild type, gray body with normal wings x double mutant, black body with vestigial wings. b+ b+ vg+ vg+ x b b vg vg
F1 result: b+ b vg+ vg and b b vg vg. Wild type & double mutant
F1 dihybrid cross: heterozygous wild-type female x homozygous double mutant male b+ b vg+ vg x b b vg vg
F2 result: b+ b vg+ vg, b b vg vg, b+ b vg vg, b b vg+ vg Wild type, black vestigial, gray-vestigial, black-normal 965 : 944 : 206 : 185
Conclusion: because most offspring maintained the parental phenotype, it was concluded that genes for body color and wing size are genetically linked on the same chromosome. However, the presence of nonparental phenotypes is indicative of a mechanism that breaks the linkage between specific alleles of genes on the same chromosome (crossing over).
Genetic Recombination – the production of offspring with combinations of traits that differ from those found in either parent.
Recombination of unlinked genes is merely the Independent Assortment of Chromosomes
Offspring with parental phenotypes are called parental types
Offspring with nonparental phenotypes are called recombinant types or recombinants.
A 50% frequency of recombination is observed for any two genes on different chromosomes.
Physical basis of recombination is due to the random orientation of homologous chromosomes at metaphase I of meiosis, which leads to the independent assortment of unlinked genes.
Crossing Over during meiosis I is the mechanism that causes the linkage between linked genes to be incomplete, it allows some recombinant phenotypes to be observed. The recombination frequency of Morgan’s fruit fly dihybrid cross was 17%
Alfred Sturtevant and Genetic Mapping
Created a genetic map that showed an ordered list of genetic loci along a particular chromosome
Predicted the farther apart two genes are, the higher the probability that a crossover will occur between them, and therefore the higher the recombination frequency.
Linkage map – a genetic map based on recombination frequencies
Distances between genes can be expressed as map units and represent a 1% recombination frequency. (indicate relative distance and order, not precise locations of genes)
Cytogenic maps - are maps that actually indicate the positions of genes with respect to chromosomal features. (This is done using methods like chromosomal banding)
Alterations of Chromosomes and Genetic Disorders Nondisjunction – the members of a pair of homologous chromosomes do not move apart properly in meiosis I, or when sister chromatids fail to separate during meiosis II. [one gamete receives two copies of that chromosome, whereas another gamete will not receive any copies of that chromosome]
This causes abnormalities in chromosome number. In mammals and humans these often lead to miscarriages, whereas plants are much more tolerant to genetic changes.
Aneuploidy
Abnormal chromosome number, results from the fertilization of a gametes in which nondisjunction occurred.
Monosomic zygote has only one copy of a particular chromosome
Trisomic zygote has three copies of a particular chromosome.
Polyploidy
A condition where an organism has more than two complete sets of chromosomes
Triploidy (3n) is three sets of chromosomes
Tetraploidy (4n) is four sets of chromosomes
More common in plants than animals, display a more normal phenotype than aneuploids.
Alterations of Chromosome Structure
Breakage of a chromosome can lead to four types of changes in chromosome structure
Deletion removes a chromosomal segment
Duplication repeats a segment
Inversion reverses orientation of a segment within a chromosome
Translocation moves a segment from one chromosome to another
Alterations of chromosome number and structure result in some serious disorders if the alterations are not fatal. These disorders have a set of symptoms characteristic of the type of aneuploidy.
Genetic Disorders
Downs Syndrome (Trisomy 21)
Three copies of chromosome 21
1/700 children born in US
Characterized by distinct facial features, short stature, heart defects, developmental delays, often under-developed and sterile.
Trisomy 18
1/7000 births increased risk of birth defects, especially the heart.
Trisomy 13
1/10000 births increased risk of birth defects, including heart, eyes, and ears.
Aneuploidy of Sex Chromosomes (nondisjunction of sex chromosomes)
Kleinfelter syndrome XXY
1/500-1000 births male sex organs, but abnormally small testes and man is sterile
Some breast enlargement and other female body characteristics are common
Subnormal intelligence
Turner syndrome X0 (monosomy X)
1/2500 female births
Only known viable human monosomy
Do not develop secondary sex characteristics, sterile
Can undergo hormone replacement therapy and will develop secondary sex characteristics.
Normal intelligence
XYY Males (Diplo Y, Jacob’s Syndrome)
1/1000 male births
No definable symptoms, but may have certain traits:
Taller than average, more acne,
XXX Females (Trisomy X)
1/1000 female births
Few symptoms but:
May be taller than average, slightly lower IQ’s, prone to learning disabilities, introverted, clumsy, awkward.
Disorders Caused by Structurally Altered Chromosomes
Cri du chat (cry of the cat) specific deletion in chromosome 5
Mentally retarded, cat-like cry
Usually die in infancy or early childhood
Chronic Myelogenous Leukemia (CML)
Caused by a reciprocal translocation during mitosis of cells that will become white blood cells.
The exchange of a large portion of chromosome 22 and a small fragment of chromosome 9, this creates a distinct shortened chromosome 22 known as the Philadelphia chromosome.
Creates BCR-abl fusion protein, a protein kinase involved in mitotic signaling
Cells constantly stimulated to divide and soon overwhelm normal blood components
*** Gleevac – a drug that targets this aberrant protein kinase, blocks ATP binding on kinase and prevents activation; Highly specific for ATP binding pocked on fusion protein. 90% of patients treated show complete remission.
Exceptions to Mendelian Genetics There are two normal exceptions. In both cases, the sex of the parent contributing the allele is a factor in the pattern of inheritance.
Genes located in the nucleus
Genomic imprinting
Variation in the phenotype depending on whether the allele is inherited from the mother or the father.
Most imprinted genes are on autosomal chromosomes and are critical for embryonic development
Occurs during gamete formation – results in the silencing of a particular allele of certain genes.
Believed to be the result of methylation of cysteine nucleotides
A zygote will only express one allele of an imprinted gene, which is inherited from either the male or the female parent.
Imprinting is “erased” in each generation and are newly imprinted in gametes that are formed.
A gene imprinted for the maternal allele expression is always imprinted this way.
Genes located outside the nucleus
Cytoplasmic Genes, or extranuclear genes, are found in organelles in the cytoplasm
Mitochondria, chloroplasts, and other plant plastids carry small circular DNA molecules.
Extranuclear genes are inherited maternally because the zygote’s cytoplasm comes from the egg.
Evidence of this came from studies on the inheritances of yellow or white patches on leaves of an otherwise green plant.
Chapter 16 Important People In Biology
Frederick Griffith – Used two strains of the streptococcus pneumoniae bacteria, one pathogenic, the S cells, and nonpathogenic, the R cells. He then injected mice with living R cells (control), living S cells (control), Heat-Killed S cells, and a mixture of Heat-Killed S cells and living R cells. The result was that the Heat-Killed S cells alone were not pathogenic and the mouse lived, and the Mixture of Heat-Killed S cells and Living R cells was pathogenic and the mouse died (There was evidence of living, replicating S cells in the blood of these mice), and therefore he concluded that the living R bacteria had been transformed into the pathogenic S bacteria by an unknown, heritable substance that allowed the R cells to make capsules.
Oswald Avery/Maclyn McCarty/Colin MacLeod – Focused on three main elements to be the unknown heritable factor from Griffith’s experiment, DNA, RNA, and proteins. Avery broke open heat-killed pathogenic bacterial cells and treated each of the three samples with an agent that inactivated one type of molecule. He discovered that only when DNA was allowed to remain active did the sample have a transforming ability. Therefore he claimed that DNA was the transforming agent but so little was known about DNA that nobody really took him seriously. (1944)
Hershey/Chase – used T2 bacteriophages one group marked with radioactive sulfur (proteins) and one marked with radioactive phosphorus (DNA) and allowed the bacteriophages to affect bacteria. The mixtures were then agitated separately to separate phage parts from outside of the bacteria, these mixtures were then centrifuged so that bacteria formed a pellet at the bottom of the test tube and radioactive phosphorous was detected in the pellet, and therefore in the bacteria cells. This allowed Hershey and Chase to conclude that viral DNA entered bacterial cells, but proteins did not, and therefore DNA is the genetic material of phage T2. (1952)
Chargaff – in 1950 reported that he found that the base composition of DNA varies from one species to another. Meaning that humans have a different base pair composition than a dog would etc. He also found that the amount of adenine = thymine and the amount of guanine = cytosine, for example in humans, A= 30.3%, T= 30.3%, G = 19.5 %, and C = 19.9%.
Watson/Crick – used Rosalind Franklin’s X-ray crystallography to predict the double helix formation of DNA, they lined the sugar-phosphate backbones in an antiparallel manner (5’3’, 3’5’). They used the X-ray measurements to discover that in DNA a pyrimidine bonds with a purine, and that A bonds with only T and C bonds with only G and vice versa. Their model also predicts a semiconservative model of replication.
Matthew Meselson – cultured E. coli in medium with a heavier nitrogen isotope then transferred the bacteria into a medium with a lighter nitrogen isotope. A sample was taken and centrifuged after one DNA replication and then again after a second DNA replication. The centrifuged results showed a mid-density radioactive pellet, the second showed a mid density radioactive pellet and a lighter density radioactive pellet this information is consistent with the predicted semiconservative replication model of DNA.
DNA Replication Basic Terms:
Origin of Replication – where the replication of a DNA molecule begins. They have a specific sequence of nucleotides indicating a start of replication. The two strands are opened up and a replication “bubble” forms
Replication Fork – a Y- shaped region where parental DNA strands are being unwound.
Helicase – enzymes that untwist the double helix that the replication fork , separating the two parental strands making them available as template strands.
Single Strand Binding Proteins – bind to unpaired DNA strands after parental strands have been separated to stabilize the unpaired DNA and prevent it from re-pairing.
Topoisomerase – helps to relieve stress that occurs ahead of the replication fork as DNA is unwound. It does this by breaking, swiveling, and rejoining DNA strands.
Primer – a short stretch of RNA that is used to prime a DNA strand for DNA replication as the proteins used for DNA replication cannot initiate synthesis of a polynucleotide on their own.
Primase – the enzyme that synthesizes RNA primers. Primase starts the complementary RNA primer from a single nucleotide and then adds RNA nucleotides one at a time using the parental strand as a template. A completed primer is generally 5-10 nucleotides long.
* New DNA can only be added to the 3’ end of the primer.
DNA Polymerase – catalyzes the synthesis of a new DNA strand by adding nucleotides to an already existing chain (the primer)
Leading Strand – because nucleotides can only be added to the 3’ end of a DNA chain, and DNA is antiparallel, the leading strand is the strand that is added continuously in the 5’3’ direction (on the parental DNA going in the 3’5’ direction). Towards the replication fork
Lagging Strand – the strand of DNA forming whose template during replication goes in the 5’3’ and therefore DNA cannot be added continuously in on the 3’, it has to be added away from the replication fork and is added in fragments known as Okazaki fragments.
* DNA polymerase I replaces RNA primer strands in the 5’3’ direction, resulting in a continuous DNA strand.
DNA ligase – joins the phosphate-sugar backbones of all the Okazaki fragments.
Mismatch repair – a method of removing and replacing incorrectly paired nucleotides that resulted from a replication error one type can be seen below:
Nuclease Excision Repair
Teams of enzymes detect and repair damaged DNA (such as thymine dimers etc. can be caused by UV radiation) which distorts the DNA molecule
A nuclease enzyme cuts the damaged DNA strand at two point, and the damaged section is removed
Repair synthesis by a DNA polymerase fills in the missing nucleotides
DNA ligase seals the free end of the new DNA to the old DNA, making the strand complete.
Nuclease – DNA cutting enzyme, that helps to excise damaged DNA bases.
* The 5’ end of the final RNA primer on the lagging strand can never be replaced with DNA because you cannot add to the 5’ end of DNA therefore DNA shortens with each replication this is why we need telomeres
Telomeres – special nucleotide sequences at the end of DNA that helps to protect the degradation of DNA. Do not contain genes but rather many repetitions of one short nucleotide sequence. Degradation of telomeres is said to be associated with aging.
Telomerase – enzyme that catalyzes the lengthening of telomeres in eukaryotic germ cells, which restores the DNA length compensating for the shortening that occurs during replication.
DNA Packaging and Chromatin
Nucleoid – the dense region in a bacteria cell that contains DNA
DNA is condensed into chromosomes by wrapping around histones and forming nucleosomes (beads on a string) these coil or fold forming a 30 nm chromatin fiber, this fiber then forms looped domains and forms into a 300 nm fiber. These then coil and fold into the distinct chromosome shape. Chromatin – complex of DNA and proteins (histones). Heterochromatin – interphase-type chromatin that is tightly packed Euchromatin – loosely packed chromatin