BIOL 1013 - BIOLOGY OF THE CELL

The following text and material represent a copy of some of my notes that formed the basis of some of my lectures given during the third portion of the Biology of the Cell (BIOL 1013) course.  Please refer to your own notes, handouts, and to the textbook (essential cell biology, 2nd edition, by Alberts, et al. 2004 - reading assignments are in the syllabus) for additional information.  If you note any errors in the following document, I'd appreciate it if you would bring this to my attention.  Email address: mhuss@astate.edu

CELL CYCLE  AND CELL DIVISON- For additional information refer to Chapters 19 & 20 in the textbook.

Cellular reproduction Life gives rise to life (19th century notion of "Spontaneous Generation" dispelled by work of Louis Pasteur) Organisms give rise to other organisms. Cells give rise to cells. Cells divide so that growth and/or reproduction can take place. Prokaryotes (i.e., bacteria, blue-green algae) are single-celled and reproduce through the process of binary fission. The circular loop of DNA (the genome) replicates and the cell divides into two equal halves.   Mitochondria and chloroplasts also reproduce by binary fission (these organelles are maternally inherited). Eukaryotes have a nucleus and in the nucleus resides chromatin or uncondensed chromosomes. Chromatin is approximately 40 % DNA and 60% protein.  DNA is tightly coiled and this coiling, packaging, and scaffolding of the DNA is facilitated by the protein. Chromatin exists as heterochromatin and euchromatin.  Heterochromatin is tightly coiled, therefore the DNA is not exposed, whereas euchromatin is less tightly coiled and is exposed.  Exposed DNA can be expressed to produce RNA and protein. Chromosomes can exist in an uncondensed or condensed state. Chromosomes can exist in an unduplicated or duplicated state (2 sister chromatids attached at the centromere. Homologous chromosomes or homologues represent pairs of chromosomes that are similar in structure, morphology, centromere position and genes that they carry. Centromere = primary constriction - site of spindle fiber attachment during mitosis and meiosis. Chromosome number and karyotypes (arranged from biggest to smallest) Locus (plural - loci) - the physical location of a gene on a chromosome Humans possess 23 pairs of chromosomes or a total of 46 chromosomes. Other examples include: chimpanzees (Pan) and gorillas (Gorilla) = 24 pairs of chromosomes (2N = 48) dogs, wolves, foxes, coyotes are all members of the genus Canis = 39 pairs of chromosomes (2N = 78) cats = 19 pairs of chromosomes (2N = 38) peas = 7 pairs of chromosomes(2N = 14) onions = 8 pairs of chromosomes (2N = 16) fruit flies = 4 pairs of chromosomes (2N = 8) male donkey, Equus asinus, 31 pairs of chromosomes (2N=62) female horse, Equus caballus, 32 pairs of chromosomes (2N=64) mule (the sterile offspring of a horse and donkey), 31 pairs of chromosomes  + 1 lone chromosome (2N = 63). Most chromosomes in a set are called autosomal chromosomes (autosomes); in many organisms one pair exists that differ from autosomal chromosomes.  These are called the sex chromosomes and function to control certain aspects of the gender of the individuals which possess certain combinations. Growth, replacement of dead cells, and/or asexual reproduction. Mitosis (nuclear division) + cytokinesis (cytoplasmic division).  No change in the genetic makeup of the individual cell (chromosome numbers remain constant). Cell division - mitosis and cytokinesis. G1 (gap 1 - interval before DNA replication) ====> S (synthesis - replication of DNA and synthesis of proteins found in chromatin/chromosomes) ====> G2 (gap 2 - interval before onset of mitosis) G1, S, and G2 represent Interphase. Movement of chromosomes is coordinated by organized arrays of microtubules - the spindle apparatus. Prophase ==> Metaphase ==> Anaphase ==> Telophase Formation of haploid cells for use in producing spores or gametes Meiosis (reduction division) + cytokinesis (cytoplasmic division). Chromosome numbers reduced by half.  General Overview of Meiosis 1. Diploid cell (2N) containing 2 sets of chromosomes gives rise to haploid cells (1N) containing one set of chromosomes. Meiosis is a reduction division that produces a spore OR a gamete (i.e., an egg or sperm). 2. Meiosis is divided into two parts: meiosis I (pairing of homologous chromosomes, crossing-over, and separation of homologues to separate cells); meiosis II (separation of non-identical sister chromatids into sister chromatids which go to separate poles of a dividing cell - refer to Figure 9-12 on page 175 in the textbook.). In plants and fungi, these haploid nuclei become integrated into specialized cells = spores. Terminology and figures for understanding meiosis and related topics homologous chromosomes - pairs of chromosomes similar in structure, morphology, centromere position and genes that they carry). synapsis - pairing of homologues during prophase I. bivalent - one of the pairs of homologous chromosomes which associate during the first prophase of meiosis. chiasmata - the points at which homologous chromosomes remain in contact as the chromatids move apart during the first prophase of meiosis. There may be up to eight chiasmata in a bivalent pair of chromosomes. chiasma (sing.) gene linkage - two genes or loci are located on the same chromosome. The closer these two genes are positioned together on the same chromosome the less likely these will appear to assort independently during meiosis.  This fact allows geneticists to construct linkage maps of the genomes of different organisms, including humans, e.g., the HUMAN GENOME PROJECT 2 Divisions occur in Meiosis (Meiosis I and Meiosis II) MEIOSIS I Prophase I Leptotene - chromatin condenses into individual chromosomes. Zygotene - pairing of homologues begins (synapsis). Pachytene - synapsis complete and chromosomes thicken and shorten. Diplotene - paired chromosomes begin to repel one another ==> chiasmata (points along paired homologues where both are still connected).  This stage is associated with crossing-over! Diakinesis - maximum contraction, paired chromosomes, nuclear membrane and nuclei breakdown. Metaphase I - chromosomes migrate to middle part of cell; spindle fibers attach to centromere; Process is random - INDEPENDENT ASSORTMENT. Anaphase I - Homologues (i.e., parental chromosomes) separate and move to opposite poles. Humans have 223 or 8,388,608 possible combinations of chromosomes that can end up in a gamete. With fertilization, this number is squared (8,388,608)2 = 70 trillion possible zygotes that can arise from a single mating event between two people! You're not one in a million, you're one in 70 trillion! And that's not counting the effects of crossing-over! Illustrates the point that the purpose of meiosis is not just about reproduction or sex, its about creating novel genetic combinations. Crossing-over and genetic recombination Homologous chromosomes assort independently Fertilization - two different gametes fuse bring together different combination of alleles. Telophase I - two haploid sets of chromosomes now exist, each set at the opposite pole of cell. MEIOSIS II Prophase II - chromosomes condense. Metaphase II - chromosomes move to middle part of cell. Anaphase II - separation of non-identical sister chromatids into sister chromosomes. Telophase II - nuclei reform and you are left with 4 haploid nuclei. For some great animations demonstrating the major events of meiosis visit:  http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter12/animations.html GAMETOGENESIS IN ANIMALS LEADS TO THE FORMATION OF GAMETES The products of meiosis must undergo differentiation in order to become functional gametes. Spermatogenesis - 4 small sperm (cytokinesis divides the cytoplasm equally) - QUANTITY! Oogenesis - 1 large ovum or egg and 3 small polar bodies (cytokinesis divides the cytoplasm unequally) - QUALITY! In other organisms, such as fungi and plants, the products lead to production of haploid spores and not directly to gametes.   This process is called sporogenesis. Polyploidy - a genetic accident that leads to more than two sets of chromosomes nucleus;  lethal in most animals; more common in plants (e.g., rutabaga, wheat, many fern species are polyploids). Aneuploidy - consequence of nondisjunction (failure of paired homologues to separate during meiosis) leads to more or less chromosomes numbers in the resulting gametes.  The fusion of a sperm and an egg results in a fertilized egg (and embryo, if viable) that contains more or less chromosomes than the "typical chromosome number"  Trisomy 21 (possession of three 21 chromosomes leads to a condition called Down Syndrome.

MENDELIAN GENETICS - Review Chapter 20 in the textbook, the text and links provided below.

Genetics (Biology of Heredity):  A Unifying Theme in Biology

THE BASIS OF HEREDITY - HYPOTHESES FOR THE MECHANISM OF HEREDITY

1. Pangenesis - A hypothesis supported to some degree by Darwin to explain the hereditary process, involving the passage into the gametes of a gemmule from each part of the body, conveying information about the exact nature of that body part. Not supported by experimental data! Rejected view! 

2. Blending Inheritance - the pre-Mendelian concept that progeny resulted from a blending of the traits of two sexually reproducing parents, with consequent loss of genetic variation on which natural selection could act.  Not supported by experimental data. Blending Inheritance was also considered by Darwin and his contemporaries as a means for explaining how traits were inherited.  Rejected view!

3. Particulate theory of inheritance - the theory, derived from Mendel's research, that characters are inherited as if they were particles, separating independently into gametes so that each variant of a character is maintained in a population in the absence of evolutionary change. Supported by experimental data!!! Accepted view! 

MENDEL'S DIHYBRID CROSS WITH PEA PLANTS

Phenotypes that result include: 9:3:3:1 or 9 Purple/Yellow: 3 Purple/Green:3 White/Yellow: 1White/Green.

These phenotypes result from the following genotypes (blanks can represent a dominant or recessive allele, doesn't matter). 9 P__Y__: 3 P__yy: 3 ppY__: 1 ppyy

PRINCIPLE OR LAW OF INDEPENDENT ASSORTMENT - The dihybrid cross demonstrated that factors controlling two or more contrasting pairs of characteristics segregate independently and that gametes combine at random.

The law of independent assortment worked for Mendel, because each trait is controlled as though genes occurred on different homologous pairs of chromosomes, and the fact that homologues assort independently during meiosis.

BEYOND MENDELIAN GENETICS (What Mendel didn't know!)

Incomplete dominance - blending inheritance resulting from neither allele masking the expression of the other allele (Snapdragon plants - Red flowered plants R¹R¹ crossed with white flowered plant R²R² yield progeny with pink flowers ===> R¹R²). A cross between two heterozygous plants for flower color yields a 1:2:1 genotypic and phenotypic ratio! To confirm these findings perform a Punnett square and check it out.

CODOMINANCE - both alleles are expressed (e.g., A and B antigens on red blood cells (RBCs) in humans for someone who has a blood type of AB; individuals heterozygous for two isozymes - alternate forms of the same enzyme - both are expressed).

ABO blood typing ===> three alleles ===> I^A, I^B or i (the null allele).  Each allele causes the production of a membrane-bound protein or antigen.

Rhesus or Rh factor is a separate antigen found in the cell membrane. Its presence makes a person positive (+), its absence makes that person negative (-). Understanding the underlying basis of blood typing can be useful in: matching donors to recipients for blood transfusions, paternity suits, and criminal cases (where bodily fluid is left at the scene of the crime).

Example: A type B woman accuses a type O man of being the father of her child. Is it possible for the the accused man to be the father of the child, if he is type A? No! The child must receive at least one I^A allele from one of the two parents. This allele could not have come from the mother (she does not possess this allele), so it must have come from the father. The accused man is type O, so his genotype is ii. He can not be the father of the child.

Blood typing can only eliminate individuals, but matches required further genetic testing (e.g., DNA fingerprinting) to confirm biological relationships.

Finally among humans, i is the most common allele, surpassing the incidence of alleles, I^A and I^B. Therefore, just because an allele is recessive, does not necessarily mean that it is less common compared to dominant alleles.

Sex linkage and Gene linkage - Refer to Thomas Hunt Morgan's experiments on fruit flies (Drosophila melanogaster):  Examples of sex-linked phenotypes in humans resulting from the expression of a specific allele occupying a locus on a sex chromosome include: hemophilia (a blood-clotting disorder) with the gene located on the X chromosome; hairy ears in males with the gene located on the Y chromosome.

MENDELIAN GENETIC PRACTICE PROBLEMS - GO TO TOP OF PAGE AND VISIT THE LINK LISTED TO PRACTICE THE PROBLEMS GIVEN IN THE MENDELIAN GENETICS - PROBLEM SET;  CHECK YOUR ANSWERS BY VISITING THE LINK TO SOLUTIONS TO MENDELIAN GENETICS PROBLEMS.

EPISTASIS - interactions of one gene with other genes can mask the effect of other genes. Modifier genes

Albinism - complete absence of melanin (a pigment located in hair, fur, skin, feathers, etc.).

Series of biochemical reactions lead to formation of melanin.  If the enzyme tyrosinase is not produced due to a mutation in a gene then no melanin can form.  The result is an albino animal.

Chemical precursors ====> =====> ====> tyrosinase ======> =====> melanin

Albinism has been observed in white rabbits, laboratory mice, humans, squirrels (such squirrels occur in Jonesboro - personal observation), deer (female deer or doe sighted by student near northeast Arkansas in Fall 2003), moose, ravens, kangaroos, etc.

An albino kangaroo from Australia - photograph by B. Buerkle (2000); Albino Squirrel and normal squirrel - photograph from http://gargles.net/wp-content/uploads/2006/07/albinosquirrelhy4.jpg.

PLEIOTROPY - gene expression where one gene exerts effect on seemingly unrelated aspects of an individual's phenotype.  Example:  Sickle cell anemia and cystic fibrosis.

sickle-cell anemia ===> disease is result of a single gene that has mutated (hemoglobin).

HbA (normal hemoglobin vs. HbS - sickle cell type hemoglobin (due to one amino acid substitution) ===> Both types of protein can be discriminated from one another by how fast they travel through a gel subject to an electrical field (electrophoresis).

POLYGENIC EXPRESSION OF TRAITS: Many phenotypes are the result of many genes interacting with one another.

EFFECTS OF THE ENVIRONMENT ON GENETIC EXPRESSION

Himalayan rabbits and siamese cats (fur on extremities are black, rest of body fur is white to gray in color). Melanin is the pigment deposited in fur that creates dark fur. Melanin production requires a temperature sensitive form of tyrosinase.

c^t = recessive allele for gene producing temperature-sensitve form of tyrosinase

c^tc^t ===> warm ===> no pigment

c^tc^t ===> cold ===> pigment present

Interaction of genes with genes and the genotype with the environment that leads to the phenotype (observable traits). For example, identical twins share the same genotype but are seldom identical in all respects due to the influence of the environment on their growth and development.  In another example, people on average, are taller today than they were one hundred years ago due to better nutrition, not due to better genes!

FINAL COMPREHENSIVE EXAM - May 2, 2008 FROM 8:00-10:00 AM