Mitosis: Chromosome Replication & Division
Grade Level		Prospective and Practicing K-8 Teachers; may be adapted for use in elementary classes.
Time		Exercises 1 & 2 take approximately 2 1/2 hours.
To Ponder		1.	How does a human being grow from a single fertilized cell into an individual containing billions of cells? Cells increase their number through a process called cytokinesis or cell division. Cell division is preceded by nuclear division or mitosis. The genetic information of the parent cell is reproduced precisely in each daughter cell, whereas division of the other cell components is more approximate.
		2.	Do all the cells of the body look like one another? Do they perform the same jobs? There are many different types of cells in the body which serve many different functions. A nerve cell, which conducts electrical messages, looks very different from a muscle cell, which is used to move some part of our body.
		3.	Do all the cells of the body contain the same genetic information? All cells in the body with the exception of egg and sperm have identical copies of an individualšs genetic information. Different genes are activated in different cell types.
		4.	How is the genetic blueprint that makes you who you are transmitted faithfully from one cell to the next? The faithful transmission of genetic material from one cell generation to the next is accomplished through DNA replication (in interphase) and division (mitosis). This nuclear replication and division occurs billions of times as a human being grows and develops, with great fidelity.
		5.	How long does it take for one parent cell to become two daughter cells? In humans, rapidly dividing cells, such as skin and gut divide as often as once per day. Other cells such as brain and nerve tissue divide rarely in an adult.
		6.	Are cells alive? Yes, cells are the smallest units of life. They are judged to be living because they are capable of respiration, nutrient intake, release of waste materials, faithful reproduction of themselves, movement, responsiveness, and other processes characteristic of living things.
		7.	What is a cell, anyway? Cells, sometimes referred to as the basic units of life, are the small compartments in your body which house your DNA and perform all the essential tasks required to sustain life. They are surrounded by a nuclear membrane, and contain a nucleus and many other organelles and subcellular structures.
Supplies		2 sets of white and 2 sets of red plastic knives, forks and spoons per group for chromosomes 1 large (3 ft) length and two smaller lengths (1.5 ft) of yarn for nuclear membrane white or brown paper per group scissors string for spindle fibers small rubber bands for centromeres yarn that is longer and a different color to represent cell membrane
Objectives		Once you have completed these exercises you should be able to:
		1.	Describe how cells reproduce themselves.
		2.	Explain how chromosomes are copied and distributed to each daughter cell in a precise way.
		3.	Describe the need for, and the mechanism of, conservation of hereditary material.
		4.	Be able to define and correctly use the following terms: allele, anaphase, chromosome replication, cytokinesis, diploid, DNA synthesis, gene, homologous chromosome, interphase, life cycle, metaphase, mitosis, prometaphase, prophase, replicated chromosomes, sister chromatids, spindle fibers, telophase, unreplicated chromosomes.
Background Information		Cell Division Your body is composed of more than a billion cells. Cells are continually dying, and new cells are continually being formed. An identical copy of your hereditary material is found in the nucleus of each and every somatic cell. A somatic cell is any cell in the body except for the reproductive cells in the reproductive system. This genetic blueprint is organized into 46 chapters or parts known as chromosomes. It is estimated that, on average, each chromosome contains between one and two thousand genes. A gene contains the information for making a single protein or RNA product. Every time a cell divides, each chromosome must be carefully replicated (copied) and then distributed to assure that each daughter cell gets a complete and accurate set of information. Thus, nuclear division includes successive processes of chromosome replication, separation, and distribution (Figure 1).
Figure 1: Chromosome Replication & Division Adapted from Postlethwait, J. H. & Hopson, J. L. (1995). The Nature of Life, Third Edition. San Francisco: McGraw-Hill, Inc. Figure 7.8, page 173. DNA synthesis occurs in the nucleus, producing an exact replica of every chromosome. A chromosome can be thought of as a very long DNA double helix. During replication, the double helix opens up and a new complementary strand is synthesized along each parent strand (Figure 2). This results in two identical DNA helices, each containing one original parent strand and one newly synthesized strand. Figure 2: DNA Replicating DNA synthesis occurs during the S phase of interphase. Each cell goes through a regular life cycle, similar to the cycle of life in humans. Where we might call our stages infancy, childhood, adolescence, young adult, adult, and senior, the major cell stages are interphase, mitosis, and cytokinesis. Interphase is subdivided into G1 (growth 1), S (synthesis), and G2 (growth 2), and mitosis is divided into P (prophase), PM (prometaphase), M (metaphase), A (anaphase), and T (telophase). This is shown in Figure 3. Figure 3: Cell Cycle Adapted from Postlethwait, J. H. & Hopson, J. L. (1995). The Nature of Life, Third Edition. San Francisco: McGraw-Hill, Inc. Figure 7.6, page 171. Another way to illustrate this cycle is shown in Figure 4. Figure 4: Cell Division Adapted from Postlethwait, J. H. & Hopson, J. L. (1995). The Nature of Life, Third Edition. San Francisco: McGraw-Hill, Inc. Figure 7.7, page 172. a. How many rounds of chromosome replication occur in the cell prior to mitosis? one Chromosomes replicate themselves once per cell cycle during the S phase of interphase. b. How many times does a cell divide in mitosis? once Cells divide once in mitosis.
Exercise 1		Exploring the Process of Mitotic Cell Division 1.1 Introduction
To Do		1.	You will study mitosis in the Triffle, a mythical creature with six chromosomes that look like knives, forks, and spoons. You will work out each step of the process using paper for cells, yarn for membranes, string for spindle fibers, and plastic knives, forks and spoons for .
		2.	Go through the entire process (1.1 through 1.8) several times, with each group member taking a turn as the "explainer". Follow along with the procedure below for the first one or two turns, and perform the subsequent repetitions from memory. Answer the questions about each stage as you go along, and answer them each time you go through the process. Explain your answers in your own words and your own way -- don't recite them by rote memory.
		3.	Take one large piece of paper for your cell, and use one color yarn to show the nuclear membrane and a different color yarn to show the cell membrane.
		4.	Begin with a cell and nucleus containing six chromosomes represented by two forks (one red & one white), two knives (one red & one white), and two spoons (one red & one white). This represents a diploid cell with three pairs of chromosomes (Figure 5).
Figure 5. Triffle Diploid Chromosome Set a. What does diploid mean? Diploid means that there are two copies of each chromosome in the cell. For humans, this means 22 pairs of autosomes (44 total) and 1 pair of sex chromosomes (2 total). Most higher organisms are diploid. One chromosome set is obtained from the female parent through the egg and the other chromosome set is inherited from the male parent through the sperm (or in plants, through the pollen). b. Are most human cells diploid? All human cells are diploid with the exception of sperm and egg cells. Sperm and egg cells, also known as gametes, are haploid. They only have one copy of each chromosome, or 23 chromosomes total. c. How many pairs of homologous chromosomes are present in the picture of a Triffle cell above? There are 3 pairs of homologous chromosomes in the Triffle cell, one pair each of knives, forks, and spoons, or a total of 6 unreplicated chromosomes. d. Draw a circle around each homologous pair of chromosomes in the picture above. Students should draw three circles. One should be around the two knives, another around the spoons, and a third around the forks. e. Are the homologues, (a short name for homologous chromosomes) above paired with one another in the cell, or are they independent from one another? The homologues are independent of one another. They do not pair with each other at any time during mitosis. Nonetheless, this idea (chromosome pairing) will be put forth frequently by students. They typically remember chromosome pairing from some previous study of meiosis, and they tend to 'see' replicated chromosomes as chromosome pairs. f. What is the best description of homologous chromosomes? (choose the best response) (1) they are the same size and shape (2) they contain the same types of genes in the same order (3) they generally contain different versions (alleles) of many of their genes (4) all of the above The best response is choice 4. All of these statements are true of homologous chromosomes. g. Define homologous chromosome. A diploid organism, such as a human, has two of each kind of chromosome, one from their father and one from their mother. The matching or homologous chromosomes have similar size and shape, and they carry the same genes arranged in the same order. However the particular version (allele) of each gene may not be the same on the two homologous chromosomes. For example, considering the homologous pair of knife chromosomes, let us say that one of the knives has a gene which codes for brown hair color. The other knife chromosome, while still possessing the gene for hair color, may code for blonde hair color. h. Contrast gene and allele. A gene is a section of DNA which will code for a particular product. An allele is an alternate form of that gene. For example, one allele of the hair color gene codes for a product which will make hair brown. Another allele of the hair color gene codes for a product which makes hair blonde. A different gene, this one for eye color, has an allele that codes for a product which makes eyes green. As another example, the ABO blood type is produced by a single gene with three alleles that code for A, B, or O. Any individual can receive two of these three alleles and so be blood type A, B, AB, or O.
		1.2 Interphase and Chromosome Replication
To Do		1.	Throughout interphase, the chromosomes are extended and are not visible in the light microscope (Figure 6). That is, the DNA is uncoiled. We cannot simulate this extended condition with the knives, forks, and spoons, so please imagine it. Replicate each of the chromosomes in your Triffle nucleus, pretending they are extended at the time. Do this by obtaining six more chromosomes that match the set you already have. Attach a red fork to your red fork, a white fork to your white fork, and so on with an elastic band (which will represent the centromere). In this process, each chromosome has essentially made an identical copy of itself.
Figure 6: Interphase
		2.	Your nucleus initially contained six unreplicated chromosomes, and now it contains six replicated chromosomes. The two identical copies of each chromosome, sister chromatids, remain attached at a point called the centromere (Figure 7).
Figure 7: Chromosome Centromere Adapted from Postlethwait, J. H. & Hopson, J. L. (1995). The Nature of Life, Third Edition. San Francisco: McGraw-Hill, Inc. Figure 7.4C, page 170. a. What is a chromatid made of (protein, carbohydrate, lipid, and/or DNA)? A chromatid is made of a very long double helix of DNA and the DNA is typically surrounded by histone proteins., especially during the condensed phase. b. How does a sister chromatids differ from a chromosome? A sister chromatid is one-half of a replicated chromosome. A replicated chromosome contains two identical DNA double helices held together at the centromere. They are sister chromatids until the centromere breaks, at which point they become independent daughter chromosomes. c. What is the centromere? The centromere is the site on the replicated chromosome where its two sister chromatids are attached. It appears as a constriction with two chromosome arms above and below. The parent helix has replicated along its entire length except at the centromere. d. Contrast extended and condensed chromosomes. Condensed chromosomes are long pieces of DNA that are highly associated with and wrapped around protein. Condensation is necessary for nuclear division. Extended chromosomes are long pieces of DNA that are uncoiled and largely free and cannot be seen clearly by the naked eye or with a light microscope.
		1.3. Prophase of Mitosis
To Do		1.	In prophase, the replicated chromosomes condense and become visible (Figure 8). This is the first stage of mitosis.
Figure 8. Prophase a. Are the two sister chromatids that are connected by a centromere identical to one another or do they contain different alleles? Explain. The two sister chromatids connected by a centromere are identical, barring The two copies arose through replication of a parent chromosome (Figure 2). b. As noted above, these structures are called replicated chromosomes (or, in many books, simply chromosomes). Replicated chromosomes are quite different from the unreplicated chromosomes seen earlier. Compare replicated chromosomes to unreplicated ones (by filling in the blanks below). (1) the amount of DNA in a replicated chromosome is two times the amount of DNA in an unreplicated chomosome (2) the number of copies of each gene in a replicated chromosome is two times the number of copies in an unreplicated chromosome (3) each replicated chromosome contains two (insert number) complete copies of genetic inf (4) the copies of genetic information in each chromosome are identical (identical, homologous, or complementary) c. Do you think that the homologous replicated chromosomes (the two pairs of knives, the two pairs of forks, and the two pairs of spoons) will pair with one another during mitosis? Explain. There is no pairing of homologous chromosomes during mitosis. It is often difficult to convince students that this is the case. Pairing of homologous chromosomes is essential for halving the chromosome number, which occurs in the production of egg and sperm, in a specialized process called meiosis. d. How many sister chromatids are in your Triffle nucleus in prophase? 12 e. A diploid human cell contains 46 unreplicated chromosomes in early interphase. How many sister chromatids will be present in the human cell during prophase of mitosis? 92
		1.4. Prometaphase of Mitosis
To Do		1.	In prometaphase, the nuclear membrane literally "disappears", which allows the rest of the mitotic events to occur. Remove the nuclear membrane from around the chromosomes in the nucleus of your cell.
		2.	Spindle fibers form, emanating from two structures called centrioles that have migrated to opposite poles (ends) of the cell. Spindle fibers are assembled from protein microtubules. Put spindle fibers in your cell using pieces of string and draw the centrioles on the paper at the appropriate points.
		3.	Some of the spindle fibers attach to the replicated chromosomes at their centromeres (Figure 9).
Figure 9: Prometaphase
		1.5. Metaphase of Mitosis
		1.	In metaphase, replicated chromosomes are lined up on the metaphase plane (across the center of the cell) by the spindle fibers(Figure 10). Homologous chromosomes are independent of one another. That is, homologous replicated chromosomes such as the two sets of replicated spoons ARE NOT PAIRED.
Figure 10. Metaphase
To Do		2.	Arrange your Triffle chromosomes across the center of the cell. The specific order of chromosomes and their orientation (right side up, upside down) is completely random. a. How many replicated chromosomes are on the metaphase plane in the Triffle? There are six replicated chromosomes in the cell, each with two chromatids held together at the centromere. b. How many replicated chromosomes would be on the metaphase plane in a human cell undergoing mitosis? There would be 46 replicated chromosomes in any human cell undergoing mitosis, with a total of 92 chromatids.
		1.6. Anaphase of Mitosis
To Do		1.	In anaphase, sister chromatids separate to become daughter chromosomes (Figure 11). Separate your sister chromatids to form daughter chromosomes.
Figure 11. Anaphase
		2.	Daughter chromosomes are moved toward opposite poles by the spindle fibers. Chromatids are flexible. They do not remain rigid, but rather bend on each side of the centromere as they are dragged through the cytoplasm. a. Are the daughter chromosomes replicated or unreplicated? Daughter chromosomes are now unreplicated. Each contains a single DNA double helix. b. Are the two sets of daughter chromosomes, the one moving toward the left and the other toward the right, identical or non-identical? With the exception of rare mutation events, mitosis leads to the formation of identical daughter chromosomes. Many of the same questions are asked several times in several different circumstances because these seem to be difficult ideas for students to grasp. c. Are the two sets of daughter chromosomes identical to those in the parent cell? Yes! In fact, each daughter chromosome contains one parent strand of DNA with a newly synthesized complementary strand. d. What is accomplished by this process? In mitosis, the genetic information in the chromosomes of a cell is first reproduced precisely and then the duplicate sets of information are distributed precisely to two daughter cells preserving the original genetic blueprint.
		1.7. Telophase of Mitosis
To Do		1.	Daughter chromosomes reach the poles of the cell and become extended (relaxed). The spindle fibers disappear ­ actually, the microtubulin subunits are disassembled. You can remove your spindle fibers from your cells and pretend your chromosomes are going into the extended state.
		2.	Two new nuclear membrane form, one around each set of daughter chromosomes. Use the nuclear membrane yarn to create two new nuclear membranes in your cell (Figure 12). Pinch in the yarn representing the cell membrane.
Figure 12. Telophase
		1.8. Cytokinesis
To Do		1.	An animal cell pinches in half at the center (Figure 12), from the outside in, until it has produced two separate daughter cells (Figure 13). Divide your cell in half in this manner by replacing the long yarn representing the parent cell membrane with two shorter pieces of yarn representing the membranes of the two daughter cells.
Figure 13. Cytokinesis Completed
		2.	These daughter cells are now entering the early interphase stage. Pretend that your Triffle chromosomes are becoming extended. The cells will grow to full size and, if continuing to divide, will replicate their chromosomes, and repeat the cycle again. a. Does the parent cell still exist? The parent cell no longer exists. It has divided into two. The cytoplasm and the organelles that were in the parent cell have been divided approximately in half into the two daughter cells. b. How are these daughter cells related to one another? The daughter cells are genetically identical and similar in morphology (size and shape) and function. c. How are these daughter cells related to the parent cell? The daughter cells are identical to the parent cell genetically, but they may be slightly different morphologically. If there is a morphological difference, it will be reflected in a slightly smaller cell size of one daughter and larger size of the other, since cytokinesis is not as precise as mitosis. d. Overall, what has been accomplished by mitosis? Two things have been accomplished. Mitosis results in a doubling of cell number, and it also effectively and accurately passes along the genetic material to the next generation. e. You have used your materials to model mitosis (nuclear division) and cellular division. Explain some ways in which a model differs from the actual things and processes it represents. Our model of a cell, made of paper, and our models of chromosomes, made of cutlery, are crude representations of the real things. They allow us to visualize and manipulate otherwise microscopic objects. However, it is important to be aware that the real things and processes are quite different from the models and to be aware of some of those key differences. It also helps to remember that some aspects of the model, such as the inability to illustrate the transition from condensed to extended states with cutlery, can be misleading.
		1.9. Practice through Repetition
To Do		1.	As noted above, you can go through the entire process several times, with each group member taking a turn as the "explainer". Follow along with the procedures outlined above for the first one or two turns, and then perform the subsequent repetitions from memory. You may refer to Table 1 for a rough guide, and your team mates can assist you by asking questions and giving hints.
Table 1. Cell Cycle Summary
			Interphase G1 stage Growth & development of the cell Protein synthesis S-phase Chromosome replication via DNA synthesis G2 stage Growth & development Organelle Replication Mitosis Prophase Replicated chromosomes condense Prometaphase Nuclear membrane dissolves Spindle fibers form Metaphase Replicated chromosomes align at center Anaphase Sister chromatids separate Daughter chromosomes move to poles Telophase New nuclear membranes form Spindle fibers disappear Cytokinesis Cell divides into two daughter cells
Exercise 2		Chromosomes in Humans
To Do		1.	Examine the chromosome spread in the top half of Figure 14. How do you think such a picture is obtained? A chromosome spread is made by: arresting cells in metaphase of mitosis with a drug like colchicine putting a drop of these cells on a slide, covering with a cover slip, and pressing lightly to break cells open drying and staining the pressed cells with a stain taken up by chromosomes examining under a light microscope, and photographing with a light microscope.
Figure 14. Human Chromosome Spread and Karyotype Photograph from Goodenough, U. & Levine, R. P. (1974). Genetics. San Francisco: Holt, Rinehart, & Winston. Figure 2-16, page 57.
		2.	Then examine the human karyotype in the bottom half of Figure 14. A karyotype is made by: cutting the individual chromosomes from a photograph of a chromosome spread arranging the chromosomes in matched pairs from largest to smallest numbering the chromosome pairs
Describe		3.	Relate what you have learned in this lab to: a. the growth and differentiation of tissues in babies, A baby begins with a single cell, an egg from its mother that has been fertilized by a sperm from its father. These two cells each bring in one haploid set of chromosomes that are united in a single nucleus in the fertilized egg. The fertilized egg divides by mitosis and mitotic cell division is repeated millions of times as the baby develops. At various points in the process, daughter cells differentiate to form specialized tissues. This is accomplished through regulation and differential expression of genes in different cell types. b. the use of a somatic cell rather than sperm and egg to create a new organism such as a sheep or frog, The fact that an entire new organism can develop from a diploid somatic (body) cell as well as from the union of two specialized haploid germ cells is pretty remarkable. Of course, this only happens under very specialized experimental conditions. The organism that is formed in this way will be genetically identical to the parent cell and to the individual from which that parent cell was taken, rather than being a blend of two parents. For this reason it is called a clone. c. another related phenomenon of your own choosing.

Supplementary Resources		Goodenough, U. & Levine, R. P. (1974). Genetics. San Francisco: Holt, Rinehart, & Winston. Figure 2-16, page 57. Klug, W. S. & Cummings, M. R. (1997). Concepts of Genetics, Fifth Edition. Upper Saddle River, NJ: Prentice Hall. Postlethwait, J. H. & Hopson, J. L. (1995). The Nature of Life, Third Edition. San Francisco: McGraw-Hill, Inc. The Biology Project, University of Arizona The Cell Cycle Graphic Illustrations Access Excellence University of Texas
Related AAAS Benchmarks		Chapter 5: THE LIVING ENVIRONMENT Section B: Heredity Grade 6-8 (Benchmark 1 of 3) In some kinds of organisms, all the genes come from a single parent, whereas in organisms that have sexes, typically half of the genes come from each parent. Section B: Heredity Grade 9-12 (Benchmark 1 of 6) Some new gene combinations make little difference, some can produce organisms with new and perhaps enhanced capabilities, and some can be deleterious. Section F: Evolution of Life Grade 9-12 (Benchmark 4 of 9) Heritable characteristics can be observed at molecular and whole-organism levels--in structure, chemistry, or behavior. These characteristics strongly influence what capabilities an organism will have and how it will react, and therefore influence how likely it is to survive and reproduce. Section B: Heredity Grade 9-12 (Benchmark 6 of 6) The many body cells in an individual can be very different from one another, even though they are all descended from a single cell and thus have essentially identical genetic instructions. Different parts of the instructions are used in different types of cells, influenced by the cell's environment and past history. Section C: Cells Grade 3-5 (Benchmark 2 of 2) Microscopes make it possible to see that living things are made mostly of cells. Some organisms are made of a collection of similar cells that benefit from cooperating. Some organisms' cells vary greatly in appearance and perform very different roles in the organism. Section C: Cells Grade 6-8 (Benchmark 1 of 4) All living things are composed of cells, from just one to many millions, whose details usually are visible only through a microscope. Different body tissues and organs are made up of different kinds of cells. The cells in similar tissues and organs in other animals are similar to those in human beings but differ somewhat from cells found in plants. Section C: Cells Grade 9-12 (Benchmark 4 of 8) The genetic information in DNA molecules provides instructions for assembling protein molecules. The [genetic] code used is virtually the same for all life forms. Chapter 6: THE HUMAN ORGANISM Section B: Human Development Grade 9-12 (Benchmark 1 of 4) As successive generations of an embryo's cells form by division, small differences in their immediate environments cause them to develop slightly differently, by activating or inactivating different parts of the DNA information.