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UNIT 4 Chapter 12: The Cell Cycle Chapter 13: Meiosis & Sexual Life Cycles Chapter 14: Mendel & The Gene Idea Chapter 15: The Chromosomal Basis of Inheritance Chapter 16: The Molecular Basis of Inheritance Introduction to Cell Division • The cell cycle propagates a lineage of cells • The cell theory • DNA exists in the nucleus as chromatin • Chromatin = DNA + histone proteins • DNA wound around histones = nucleosomes • Chromatin is arranged into discrete structures called chromosomes • Eukaryotes all possess a characteristic number of chromosomes • During cell division, each chromosome is duplicated and held to its copy by the centromere • Each half called a sister chromatid • Chromatids are eventually separated into different cells Types of Division • All cells undergo division at some point in their life cycle • Somatic cells: mitosis = 2 daughter cells identical to 1 parent cell • 46 chromosomes (human) • Gametes (sex cells): meiosis = 4 daughter cells unique to each other and 1 parent cell • 23 chromosomes (human) • Cytokinesis is the division of the cell itself Mitosis • Mitotic phase (M) alternates with interphase • 90% of cell’s life spent in interphase • G1 = growth, daily activities • S = DNA synthesis • G2 = finalizes preparation for division • M = division of nucleus • Mitosis is a 4 step process • • • • Prophase Metaphase Anaphase Telophase • After mitosis, cells may undergo division again, or enter the G0 phase Mitosis - Prophase • Chromosomes have duplicated and centrosomes begin forming spindle fibers as they move to the poles of the cell • Spindle fibers which push on one another to move mitotic spindle • Nuclear envelope fragments and some spindle fibers interact with kinetochores • Other spindle fibers attach to spindle fibers from opposite pole Mitosis - Metaphase • Spindle fibers move the chromosomes until they reach the metaphase plate • Imaginary plane equidistant between the poles Mitosis - Anaphase • Centromeres divide, separating the sister chromatids • Chromatids (now chromosomes) “walk” along spindle fiber, moving closer to pole • Ultimately, each pole has an equivalent collection of chromosomes Mitosis - Telophase • Cell continues to elongate • Fragments of the original nuclear membrane are used to begin forming two new nuclei • Kinetochore spindle fibers disconnect from chromosomes and cytokinesis begins Cytokinesis • Cytokinesis follows mitosis • Animals: cleavage furrow forms • Plants: cell plate forms Regulation of the Cell Cycle • The frequency of cell division depends mainly on the cell type • Events in the cell cycle are controlled by a cell cycle control system • Checkpoints are control points • Cyclins are proteins involved with regulation • Growth factors are important in densitydependent inhibition • Most animal cells exhibit anchorage dependence • Cancer cells have escaped the cell cycle • Do not exhibit densitydependent inhibition or anchorage dependence • If, and when, cancer cells stop dividing, they do so at random points, not at the typical checkpoints • Most cells divide up to 50 times before they senesce • HeLa cells • Transformation occurs when a normal cell in a tissue becomes cancerous • Immune system normally destroys these cells • Cells that escape destruction continue to divide to form a tumor • Benign • Malignant END Offspring Receive Genetic Material from Parents DNA (or chromosomes) is transmitted to offspring via gametes Sperm & egg are haploid Fertilization is the union of sperm and egg Most human cells possess 46 chromosomes diploid Sequences of DNA, genes, exist on chromosomes to direct production of proteins • Genes exist at a locus, or location on a chromosome Meiosis Reduces Chromosome Number Meiosis goal: to reduce diploid cells into haploid ones Meiosis resembles mitosis, but how genetic material is segregated differs Two cell divisions: Meiosis I and Meiosis II Prophase I Homologous pairs line up to form tetrads Synapsis (crossing over) involves the swap of genetic material between non-sister chromatids Non-sister chromatids are crossed at chiasmata Metaphase I & Anaphase I Tetrads line up at metaphase plate and the homologous pairs are separated, but sister chromatids remain attached Metaphase II & Anaphase II The sister chromatids line up at metaphase plate and the chromatids are segregated to the opposite poles Sexual Life Cycles Produce Offspring Variation Three main reasons for variation exist: Crossing over Random fertilization Independent assortment Crossing over produces recombinant chromosomes, new combinations of genetic material that doesn’t exist in either parent Independent assortment Adding random fertilization and independent assortment can produce over 70 trillion chromosome combinations Crossing over adds even more possibilities! … plus, the chance of mutation. END • Mendel cross-pollinated (hybridize) two contrasting, true-breeding pea varieties – True-breeding parents are the P generation and their hybrid offspring are the F1 generation • Mendel would then allow the F1 hybrids to pollinate to produce an F2 generation • F2 plants revealed two fundamental principles of heredity: – law of segregation – law of independent assortment •A description of an organism’s traits is its phenotype •A description of its genetic makeup is its genotype Law of segregation • P generation true-breeders produced all of the same phenotype, as seen in one of the P gen. parents • When F1 plants pollinated, the F2 generation included both phenotypes seen in the P gen. • Ex. Mendel recorded 705 purple-flowered F2 plants and 224 white-flowered F2 plants from the original cross – 3:1 ratio • Law of segregation has four parts: 1. Alternative version of genes, called alleles, account for variations in inherited characters • Different alleles vary in the sequence of nucleotides at the locus of a gene 2. For each character, an organism inherits two alleles, one from each parent – Diploid (2n) organism inherits one set of chromosomes from each parent – Organism has a pair of homologous chromosomes and therefore two copies of each locus 3. If two alleles differ, then the dominant allele is fully expressed in the organism’s appearance – Recessive allele has no noticeable effect on the organism’s appearance 4. The two alleles for each character segregate (separate) during gamete production • If an organism has identical alleles (homozygous) for a particular character, then 100% of gametes produced will gain that allele • If different alleles (heterozygous) are present, then 50% of the gametes will receive one allele and 50% will receive the other Alleles Segregate into Gametes Independently • Experiments that study only a single character are called monohybrid crosses – Two different characters = a dihybrid cross The relationship between genotype and phenotype is rarely simple • Some characters reflect incomplete dominance where heterozygotes show a distinct intermediate (blended) phenotype • Codominance involves two alleles which affect the phenotype individually – Ex. Human blood types • Dominance/recessiveness relationships have three important points: 1. They range from complete dominance, though degrees of incomplete dominance, to codominance 2. They do not involve the ability of one allele to subdue another at the level of DNA 3. They do not tell how common a trait is in a population END Variation & Genetic Mapping • Offspring with new combinations of traits inherited from two parents is genetic recombination • Genetic recombination can result from: independent assortment or from crossing over • Frequency of crossing over data used for constructing a chromosome map • Map is an ordered list of the genetic loci along a particular chromosome • Frequency of recombinant offspring reflects the distances between genes on a chromosome • Genes far apart = higher probability that crossover will occur between them • The distance between genes, the recombination frequency, are called map units • 1 map unit = 1% crossover frequency • Recombination frequencies are not always additive: 9% (b-cn) + 9.5% (cn-vg) ≠ 17% (b-vg). • Second crossing over can “cancel out” the first • Genes father apart are more likely to experience multiple crossing over events • Some genes on a chromosome are so far apart that a crossover between them is virtually certain • Frequency of recombination reaches 50% • Genes act as if found on separate chromosomes Chromosomes and Sex • This X-Y system of mammals is not the only chromosomal mechanism of determining sex • Other types include the X-0 system, the Z-W system, and the haplo-diploid system • In humans, individuals with the SRY gene (on Y chromosome), the generic embryonic gonads are modified into testes • SRY gene activates a series of events to cause fetus to develop as a male • Genes on other chromosomes activated • Other genes on the Y chromosome are necessary for the production sperm • Lacking SRY? Default sex, female, develops • Sex-linked genes (and the sex chromosomes) have unique patterns of inheritance Variation in Chromosomes • Nondisjunction occurs when problems with the meiotic spindle cause errors in daughter cells • Tetrad chromosomes do not separate properly during meiosis I • Sister chromatids may fail to separate during meiosis II • Some gametes receive two of the same type of chromosome and another gamete receives no copy • Cell with abnormal (too many OR too few) number of chromosomes= aneuploid • Trisomic cells = three copies of a particular chromosome type and have 2n + 1 total chromosomes • Monosomic cells = only one copy of a particular chromosome type and have 2n - 1 chromosomes • Organisms with more than two complete sets of chromosomes, have undergone polyploidy • Could be triploid (3n) or tetraploid (4n) • Polyploidy is not tolerated in some cell types or species • Chromosomal Mutations • Four types of changes in chromosome structure: • Deletion occurs when a chromosome fragment is lost during cell division • Missing certain genes • Duplication occurs when a fragment becomes attached as an extra segment to a sister chromatid • Inversion occurs when a chromosomal fragment reattaches to the original chromosome but in the reverse orientation • Translocation, a chromosomal fragment joins a nonhomologous chromosome • Some translocations are reciprocal Examples of Human Disorders • Down Syndrome: trisomy of chromosome 21 (1/700) • Kleinfelter’s Syndrome: XXY, anatomically male but sterile, may have some female characters (1/2000) • Trisomy X: XXX, normal females (1/2000) • Turner’s Syndrome: X0, anatomically female, but immature (1/5000) Extranuclear Genes • Not all of a eukaryote cell’s genes are located in the nucleus • Extranuclear genes are found in mitochondria and chloroplasts • Not distributed to gametes during meiosis • A zygote inherits all of its mitochondria only from the ovum • Sperm provides only a haploid nucleus • Mitochondrial genes in mammals display maternal inheritance END Structure of DNA DNA is a polymer of nucleotides – Sugar, phosphate, nitrogenous base Sugar and phosphate are backbones, bases at the interior (A)denine, (T)hymine, (G)uanine, (C)ytosine – Double-stranded in twisted shape = double helix Base pairing rule: – A with T, two hydrogen bonds – G with C, three hydrogen bonds Strands are anti-parallel to one another – 5’ phosphate and 3’ OH DNA Replication: The Details … A human somatic cell can replicate its 3 billion base pairs within a few hours and only one error per billion nucleotides! More than a dozen enzymes and proteins participate in DNA replication Replication begins at numerous sites called origins of replication – Helicase first unwinds the double helix – Single-stranded binding proteins open and hold the strands apart DNA strands separate forming a “bubble” and two replication forks DNA polymerase III is primarily responsible for the addition of nucleotides – Approx. 50 nucleotides/second DNA polymerase III behaviors – It can ONLY add nucleotides to a pre-existing strand of DNA – It can ONLY add nucleotides to a 3’ OH (in eukaryotes) “Solutions” – Primase base pairs about 10 RNA nucleotides to the DNA forming a primer – The primer is removed by DNA Polymerase I and DNA nucleotides can be added, closing the gap Only one strand of the parent DNA is oriented properly 3’ 5’ into the replication fork – Leading strand can add nucleotides continuously – Lagging strand must replicate new DNA in pieces = Okazaki fragments Okazaki fragments are later joined to one another by DNA ligase DNA Replication: A Summary Leading strand is copied continuously into the fork, while the lagging strand is copied away from the fork in segments, each requiring a primer Telomeres & Telomerase The ends of the DNA molecule are replicated by a special process – The linear nature of eukaryotic chromosomes poses a problem Telomeres protect genes from being eroded as DNA is replicated – (Humans: TTAGGG repeated 100-1000 times) Telomerase restores lost telomeric sequence – Provides space for primase and DNA polymerase to extend the 5’ end Telomerase not active in somatic cells – Telomerase ACTIVE in: Germ-line cells Stem cells Cancer cells END