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Date Created: 08/27/16
Chapter 12: The Cell Cycle Cell Division: Can be used for: Reproduction Unicellular organisms divide a cell for a duplicated copy of the cell. Growth and Development A single-cell organism divides to form two cells, then four cells, and so forth. Example: a zygote Repair (Tissue Renewal) Healthy tissue is used to replace damaged tissue of an injury. Interphase- cell growth and the copying of chromosomes in preparation for cell division G1- a cell grows S- copies its chromosomes DNA synthesis G2- completes preparation for cell division The centrosomes are duplicated, uncondensed. Stages of Mitosis: Prophase The nucleoli disappear. Each duplicated chromosome appears as two identical sister chromatids. The mitotic spindle begins to form. Pro-metaphase The nuclear envelope fragments. Each of the two chromatids of each chromosome now has a kinetochore. Metaphase The mitotic spindle is fully formed. The chromosomes have arrived at the metaphase plate. Anaphase The two sister chromatids of each pair part. Each chromatid becomes a full-fledged chromosome. Telophase (and Cytokinesis) Nucleoli reappear. Two daughter nuclei form in the cell. Nuclear envelopes arise from the fragments of the parent’s cell. Two daughter cells appear. Cytokinesis involves the formation of a: Cleavage furrow (in animals) Cell plate (in plants) Binary Fission- the asexual reproduction of single-celled eukaryotes Cell Division in Prokaryotes Variants of Mitosis Bacteria Dinoflagellates (unicellular protists) Diatoms and some yeasts Most eukaryotes Endogenous (Internal) Factors Exogenous (External) Factors Cytoplasmic factor controls the cell cycle. Cyclins and Cyclin-dependent kinases (CDKs) form maturation-promoting factor (MPF). Platelet-derived growth factor (PDGF) can stimulate cell division exogenously. Cells display anchorage dependence and density dependence. Cancer cells may lose anchorage dependence and density dependence. They can produce their own growth factors or produce growth factors that trigger other cells to divide (metastasis). Definitions Genome- a cell’s genetic information Chromosome- a structure in which DNA is packaged Chromatin- the entire complex of DNA and proteins that is the building material of chromosomes Sister chromatids- joined copies of the original chromosome Somatic cell- all body cells except the reproductive cells Gamete- a reproductive cell (sperm or eggs) Zygote- a diploid cell resulting from the fusion of two haploid gametes Centromere- a region of the chromosomal DNA where the chromatid is attached most closely to its sister chromatid Mitosis- the division of the genetic material in the nucleus Cytokinesis- the division of cytoplasm Cleavage furrow- a shallow groove in the cell surface Cell plate- produced form microtubules aligning at the middle of a cell Kinetochore microtubules- They jerk the chromosome back and forth. Non-kinetochore microtubules- They interact with those from the opposite pole of the mitotic spindle. Cyclin- a protein that cyclically fluctuates concentration in the cell Cyclin-dependent factor (CDK)- Its activity rises and falls with changes in the concentration of its cyclin partner. Maturation-promoting factor (MPF)- a cyclin-CDK complex It triggers the cell’s passage into the M phase. Promotes fragmentation of the nuclear envelope (Pro-metaphase of mitosis) It contributes to chromosome condensation and spindle formation (Prophase). Platelet-derived growth factor (PDGF)- It is required for the division of cultured fibroblasts, a type of connective tissue, helping to heal wounds. Anchorage dependence- To divide, a cell must be attached to a substratum. Density dependence- Crowded cells stop dividing. Cancer- Transformation- the process that causes cells to behave like cancer cells Benign tumor- The abnormal cells remain at the original site. Malignant tumor- The abnormal cells can spread to new tissues. Metastasis- the spread of cancer cells to locations distant from the original site Chapter 13: Meiosis and Sexual Life Cycles Stages of Meiosis Meiosis I (reductional division)- Homologs pair up and separate, resulting in two haploid daughter cells with replicated chromosomes. Prophase I Crossing over occurs. Chiasmata- where crossover have occur Metaphase I Anaphase I Telophase I and Cytokinesis Two haploid daughter cells are formed. Meiosis II (equational division)- Sister chromatids separate. Prophase II Metaphase II Anaphase II Telophase II and Cytokinesis The meiotic division of one parent cell produces four daughter cells, each with a haploid set of (unduplicated) chromosomes. Life Cycles of Eukaryotes Gametic meiosis Gametes are the only haploid cells. Zygotic meiosis After fertilization, the diploid zygote divides by mitosis, producing a multicellular organism that is diploid. Alternation of generations Sporophyte- the multicellular diploid stage Meiosis produces spores (haploid cells). A haploid spore divides mitotically. Gametopyte- a multicellular haploid stage Fusion of two haploid gametes at fertilization result in a diploid zygote, which develops into the next sporophyte generation. Crossing Over (Synapsis) Occurs only during Prophase I Anaphase I: the separation of homologous chromosomes Anaphase II: the separation of sister chromatids Mitosis VS. Meiosis Similarities Differences Crossing over, independent assortment and random fertilization all contribute to genetic variability. Definitions: Genetics- the study of heredity and variation Variation- the differences in the appearance of offspring from their parents and siblings Heredity- the transmission of traits from one generation to the next Meiosis- a type of cell division that reduces the number of sets of chromosomes from two to one in the gametes Homologous chromosomes- Two chromosomes of a pair have the same length, centromere position, and staining patterns. Genes- heredity units Locus (pl. loci)- a gene’s specific location along the length of a chromosome Asexual reproduction- A single individual is the sole parent and passes copies of all its genes to its offspring without the fusion of gametes. Clone- a group of genetically identical individuals Sexual reproduction- Two parents give rise to offspring that have unique combinations of genes inherited from the two parents. Karyotype- Images of chromosomes are arranged in pairs. Autosomes- other chromosomes beside the sex chromosomes Sex chromosomes- the X and Y chromosomes Haploid- a cell containing a single set of chromosomes Diploid- a cell with two chromosome sets Recombinant chromosome- a chromosome with a new combination of genes not found together in either parent Chapter 14: Mendel and the Gene Idea Particulate VS. Blending Hypotheses for Inheritance Particualte Hypothesis Parents pass on discrete heritable units (genes). Blending Hypothesis Genetic material from the two parents blends together. Gregor Mendel- a monk who experimented with garden peas in the mid 1800s Why were peas a good model organism? There are many varieties. Short generation time Large number of offspring Mating could be controlled. Self- pollination or cross pollination Law of segregation- Two forms of a character (alleles) separate during gamete formation and are distributed to the gametes. E.g. purple and white flowers Law of independent assortment- Genes for different traits are not always inherited together. E.g. round yellow peas and green wrinkled peas Complete Dominance VS. Incomplete Dominance VS. Codominance Pedigree analysis can be used to track inheritance patterns in humans. Definitions: Trait- each variant of a character Character- a heritable feature that varies among individuals True-breeding- Many generations of self-pollination produces the same variety of the parent plant. Homozygous- describes an organism with a pair of identical alleles for a gene Heterozygous- describes an organism with tow different alleles for a gene Hybridization- the crossing of two true-breeding parents P-generation- the parental generation F1-generation- the first filial generation F2-generation- the second filial generation Alleles- the alternate versions of genes Dominant allele- determines an organism’s appearance Recessive allele- has no noticeable effect on an organism’s appearance Punnett square- a diagrammatic device for predicting allele composition of offspring Phenotype- an organism’s appearance or observable traits Genotype- an organism’s genetic makeup Testcross- breeding and organism of unknown genotype with a recessive homozygote Monohybrid- an individual heterozygous for one particular gene Dihybrid- an individual heterozygous for two genes Complete dominance- Phenotypes are indistinguishable. Incomplete dominance- a phenotype somewhere between those of the two parent varieties Codominance- Two alleles affect the phenotype in separate, distinguishable ways. Multiple alleles- Moat genes exist in more than two allelic forms. Pleiotropy- genes having multiple phenotypic effects Epistasis- the phenotypic expression of a gene at one locus alters that of a gene at a second locus Quantitative characteristics- Characters vary in the population I gradation along a continuum. Polygenic inheritance- an additive effect of two or more genes on a single phenotypic character Multifactorial- Many factors, both genetic and environmental, collectively influence phenotype. Pedigree- a family tree describing the trait of parents and children across generations Carrier- Heterozygotes may transmit the recessive allele to their offspring. Sickle-cell allele Chapter 15: The Chromosomal Basis of Inheritance Thomas Hunt Morgan- a geneticist of the early 20 century Worked with fruit flies (Drosophila melanogaster) Why were fruit flies a good model organism? Produce many offspring Generation time: 2 weeks Four pairs of chromosomes XY sex determination schema Produced many mutant forms of D. melanogaster “Wild-type”- the “normal” fruit fly He crossed white-eye mutants with red-eyed wild type flies. F1 generation: all red-eyed F2 generation: 3 red, 1 white Only the males had white eyes. The white-eye gene was located on the X- chromosome. Organisms that do not have XY sex determination schema: Grasshoppers: X-O system Women are XX; males are X. Chickens: Z-W system Women are ZW; men are ZZ. Insects (Ant, Bees): haploid-diploid system Women are diploid; men are haploid. X-linked, Recessive Characteristic Males will express the recessive phenotype much more frequently than females. Examples: red-green colorblindness, hemophilia In females, one copy of the X chromosome is shut off, inactivated, and forms a Barr body. During development, certain cell lineages in the same organism will express different phenotypes if she is heterozygous for a locus on the X chromosomes. Calico phenotype in cats and lobsters Gene Linkage In a dihybrid cross, Morgan observed ratios of progeny that differed from Mendel’s expectations. Crossed grey-bodied, normal winged flies with black- bodied, vestigial winged flies F1 generation: all grey-bodied, normal winged flies (as predicted by Mendel) F2 generation: Morgan got a very different ratio of offspring. Genes for body color and wing type were linked together on the same chromosome. Morgan calculated recombination frequency. = (the number of recombinants/the total offspring) X 100 Alfred Sturtevant- Morgan’s student Developed a linkage map by performing crossed and calculating recombination frequencies four linkage groups, which provided further evidence for the chromosomal basis of inheritance (b/c fruit flies have four sets of homologous chromosomes). Many genetic disorders are the result of errors at the chromosomal level, either due to entire chromosomes being misassigned to gametes (aneuploidy) or to damage to parts of chromosomes. Aneuploidy results when the homologs or sister chromatids are not properly attached to the microtubules, and one cell receives all or none of the corresponding chromosome (non-disjunction). Plants are more tolerant of aneuploidy than animals and are usually polyploidy. Examples of aneuploidy: Trisomy 21 (Down Syndrome) Klinefelter Syndrome (XXY) Triple X Syndrome (XXX) Turner Syndrome (XO) Parts of chromosomes can be deleted, inverted, translocated, or duplicated. Can lead to structures like Philadelphia chromosomes and conditions such as cri du chat Definitions: Chromosomal theory of inheritance- Mendelian genes have specific loci (positions) along chrom0somes, and it is the chromosomes that undergo segregation and independent assortment. Hemizygous- having only a single copy of a gene Sex-linked gene- a gene located on either sex chromosome X-linked gene- a gene of the X chromosome Y-linked gene- a gene of the Y chromosome Barr body- the inactive X in each cell of a female Aneuploidy- A zygote has an abnormal number of a particular chromosome. Non-disjunction- Gametes have not enough or too many chromosomes. Monosomy- A chromosome is missing in the zygote. Trisomy- A chromosome is present in triplicate in the zygote. Deletion- A chromosomal fragment is lost Inversion- A chromosomal fragment is reattached in the reverse orientation. Duplication- A deleted chromosomal fragment is attached as an extra segment to a sister chromatid. Translocation- A chromosomal fragment joins a non-homologous chromosome. Reciprocal translocation Chapter 16: The Molecular Basis of Inheritance Watson and Crick (and Wilkins and Franklin) DNA is a double helix with the nitrogenous bases hydrogen bonding to each other in the central part and the sugars and phosphates forming a covalently bonded backbone. Sugar phosphate backbones on either side run antiparallel, 5’ to 3’ on one strand and 3’ to 5’ on the opposite strand. Purines base pair with pyrimidines and vise versa. A and T form two hydrogen bonds, and C and G form three hydrogen bonds. Proof that DNA is the genetic material that can transfer cellular information chemically Griffith Infected mice with two strains of bacteria, one pathogenic (disease- causing, S strain) and the other harmless (R- strain) Live S strain alone killed mice. Live R strain alone did not. Heat killed S strain alone. It did not with Live R strain. Heat killed S strain and live R strain killed the mice, and Griffith reisolated live S strain. Something in the dead bacteria was being picked up by the live bacteria and transforming them. Hershey and Chase 35 32 Used radioactively labeled protein ( S) and DNA ( P) to infect E. coli bacteria with bacteriophage Only the P-label was detected in the bacteria. DNA must be getting into the bacteria and infecting them, not the protein. Chargaff Discovered different organisms have different ratios of the four nucleotides, but A=T and G=C Support for DNA as genetic material and data about composition “Chargaff’s rules” Meselson and Stahl: Demonstrated the semiconservative nature of DNA replication Each strand has new nucleotides added so each replicated molecule is half old and half new. DNA replication begins at the origins of replication (ori sites) that are recognized by the DNA replication machine. A replication bubble opens, as the two strands are pulled apart by helicase and the strands held apart by single-strand binding proteins. Topoisomerase prevents overwinding of the DNA, like the strands of a string. In order to make new DNA, there must be a free 3’-OH group to add the new nucleotides onto. There must be a short (5-10 nucleotide) primer of RNA added by the enzyme primase. Produces a free 3’-OH that DNA polymerase III can build upon The rate of elongation (adding of nucleotides) is faster in prokaryotes than eukaryotes. The nucleotides that are added are deoxyribonucleotide triphosphates (dNTPs), with deoxyribose for the 5 carbons. When dNTPs are added, the energy to catalyze the reaction comes from cleaving off the two terminal phosphates as a molecule of pyrophosphate. Chapter 17: Gene Expression: From Gene to Protein Beadle and Tatum: Experimented with Neurospora crassa (bread mold fungus) Demonstrated the one gene to one polypeptide hypothesis Each gene dictates the production of a specific enzyme. Gene expression- the central dogma of molecular biology DNA is transcribed to produce RNA (mRNA). mRNA is translated to produce polypeptide. The Genetic Code mRNA encodes amino acids (AA) via triplet code; 3 nucleotide words makes a codon. 64 codons (4X4X4) 3 stop codons (UAA, UAG, UGA) to end translation 1 start codon (AUG, also encodes AA methionine) There is redundancy but no overlap in AA coding. The code is almost universal; any organism can express a gene from any other organism. Prokaryotic VS. Eukaryotic Gene Expression Prokaryotes Eukaryotes Transcription progresses a a rate of 40 nucleotides per second. Transcription and translation are spatially separated in euks. Transcription and translation are simultaneous in proks. Transcription DNA to mRNA Three stages: Initiation- starting Elongation- adding nucleotides Termination- ending A promoter binds transcription factors and RNA polymerase II. RNA polymerase II reads the template strand of the DNA in the 3’ to 5’ direction and makes a complementary RNA strand in the 5’ to 3’ direction. Prokaryotes have a terminator sequence to terminate transcription. Eukaryotes have a polyadenylation signal (-AAAAAAAAAAAA), Post-Transcriptional Processing in Euks Polyadenylation G-capping at 5’ end A guanine nucleotide is added to the front end of mRNA; however, it’s attached backwards. Splicing of introns by snRNPs and the spliceosome Alternate splicing leads to different gene products (doesn’t happen in proks). Translation Occurs at ribosomes in cytoplasm Three stages: Initiation Elongation Termination tRNA carries amino acids and has anticodons that complement codons in mRNA. Ribosomes made up of protein and rRNA, have small and large subunits. Three sites in large subunit: P (Peptide) site Holds the tRNA that carries the growing polypeptide chain A (Amino) site Holds the tRNA that carries the next amino acid to be added to the chain E (Exit) site Where discharged tRNAs leave the ribosome mRNA is read in 5’ to 3’ direct Mutations- changes in the genetic material of a cell Point mutations- chemical changes in just one base pair of a gene Nucleotide-pair substitutions Nucleotide-pair insertions or deletions Single nucleotide changes may result in silent, missense, or nonsense mutation. Silent mutations Have no effect on the amino acid Missense mutation Code for the incorrect amino acid Nonsense mutations Change an amino acid codon into a stop codon, leading to a nonfunctional protein Insertions and deletions may cause frameshift mutations (affecting every AA downstream from the mutation). __________________________________________________________________ _______________________ Gene expression- the process by which DNA directs protein synthesis Two stages: Transcription- the synthesis of RNA using information in DNA Produces messenger RNA (mRNA) Primary transcript- the initial RNA transcript from any gene prior to processing Translation- the synthesis of a polypeptide, using information in mRNA Occurs at ribosomes The Central Dogma Cells are governed by a cellular chain of command: DNA to RNA to protein
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