DNA

Douglas Wilkin, Ph.D.Jean Brainard, Ph.D.

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AUTHORSDouglas Wilkin, Ph.D.Jean Brainard, Ph.D.CK12 Editor

www.ck12.org Chapter 1. DNA

CHAPTER 1 DNACHAPTER OUTLINE

1.1 Mitosis

1.2 Embryo Growth and Development

1.3 Stem Cells

1.4 Clones and Transgenic Organisms

1.5 References

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1.1. Mitosis www.ck12.org

1.1 Mitosis

My Learning Goals

• I can explain how mitosis contributes to growth and development in organisms.• I can describe the generalized process that results in two genetically identical daughter cells.• I can explain the role of mitosis in the cell cycle.• I can compare and contrast models of eukaryotic and prokaryotic cellular division.

Where do cells come from?

No matter what the cell, all cells come from preexisting cells through the process of cell division. The cell may bethe simplest bacterium or a complex muscle, bone, or blood cell. The cell may comprise the whole organism or bejust one cell of trillions.

Cell Division

You consist of a great many cells, but like all other organisms, you started life as a single cell. How did youdevelop from a single cell into an organism with trillions of cells? The answer is cell division. After cells grow totheir maximum size, they divide into two new cells. These new cells are small at first, but they grow quickly andeventually divide and produce more new cells. This process keeps repeating in a continuous cycle.

Cell division is the process in which one cell, called the parent cell, divides to form two new cells, referred to asdaughter cells. How this happens depends on whether the cell is prokaryotic or eukaryotic.

Cell division is simpler in prokaryotes than eukaryotes because prokaryotic cells themselves are simpler. Prokaryoticcells have a single circular chromosome, no nucleus, and few other organelles. Eukaryotic cells, in contrast, havemultiple chromosomes contained within a nucleus and many other organelles. All of these cell parts must beduplicated and then separated when the cell divides. A chromosome is a molecule of DNA, and will be the focus ofa subsequent concept.

Cell Division in Prokaryotes

Most prokaryotic cells divide by the process of binary fission. A bacterial cell dividing this way is depicted inFigure 1.1.

Binary fission can be described as a series of steps, although it is actually a continuous process. The steps aredescribed below and also illustrated in Figure 1.4 1.2. They include DNA replication, chromosome segregation, andfinally the separation into two daughter cells.

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FIGURE 1.1Binary Fission in a Bacterial Cell. Celldivision is relatively simple in prokaryoticcells. The two cells are dividing by binaryfission. Green and orange lines indicateold and newly-generated bacterial cellwalls, respectively. Eventually the parentcell will pinch apart to form two identicaldaughter cells. Left, growth at the centerof bacterial body. Right, apical growthfrom the ends of the bacterial body.

• Step 1: DNA Replication. Just before the cell divides, its DNA is copied in a process called DNA replication.This results in two identical chromosomes instead of just one. This step is necessary so that when the celldivides, each daughter cell will have its own chromosome.

• Step 2: Chromosome Segregation. The two chromosomes segregate, or separate, and move to opposite ends(known as "poles") of the cell. This occurs as each copy of DNA attaches to different parts of the cellmembrane.

• Step 3: Separation. A new plasma membrane starts growing into the center of the cell, and the cytoplasm splitsapart, forming two daughter cells. As the cell begins to pull apart, the new and the original chromosomes areseparated. The two daughter cells that result are genetically identical to each other and to the parent cell. Newcell wall must also form around the two cells.

Cell Division in Eukaryotes

Cell division is more complex in eukaryotes than prokaryotes. Prior to dividing, all the DNA in a eukaryotic cell’smultiple chromosomes is replicated. Its organelles are also duplicated. Then, when the cell divides, it occurs in twomajor steps:

1. The first step is mitosis, a multi-phase process in which the nucleus of the cell divides. During mitosis,the nuclear membrane breaks down and later reforms. The chromosomes are also sorted and separated toensure that each daughter cell receives a diploid number (2 sets) of chromosomes. In humans, that number ofchromosomes is 46 (23 pairs).

2. The second major step is cytokinesis. As in prokaryotic cells, the cytoplasm must divide. Cytokinesis is thedivision of the cytoplasm in eukaryotic cells, resulting in two genetically identical daughter cells.

The Cell Cycle

Cell division is just one of several stages that a cell goes through during its lifetime. The cell cycle is a repeatingseries of events that include growth, DNA synthesis, and cell division. The cell cycle in prokaryotes is quite simple:the cell grows, its DNA replicates, and the cell divides. In eukaryotes, the cell cycle is more complicated.

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FIGURE 1.2Steps of Binary Fission. Prokaryotic cellsdivide by binary fission. This is also howmany single-celled organisms reproduce.

FIGURE 1.3Mitosis in the Eukaryotic Cell Cycle. Mi-tosis is the multi-phase process in whichthe nucleus of a eukaryotic cell divides.

The Eukaryotic Cell Cycle

The diagram in Figure below represents the cell cycle of a eukaryotic cell. As you can see, the eukaryotic cellcycle has several phases. The mitotic phase (M) actually includes both mitosis and cytokinesis. This is whenthe nucleus and then the cytoplasm divide. The other three phases (G1, S, and G2) are generally grouped togetheras interphase. During interphase, the cell grows, performs routine life processes, and prepares to divide. Thesephases are discussed below. You can watch a eukaryotic cell going through these phases of the cell cycle at thefollowing link: http://www.cellsalive.com/cell_cycle.htm .

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FIGURE 1.4Eukaryotic Cell Cycle. This diagram rep-resents the cell cycle in eukaryotes. TheFirst Gap, Synthesis, and Second Gapphases make up interphase (I). The M(mitotic) phase includes mitosis and cy-tokinesis. After the M phase, two cellsresult.

Summary

• Cell division is part of the life cycle of virtually all cells. Cell division is the process in which one cell dividesto form two new cells.

• Most prokaryotic cells divide by the process of binary fission.• In eukaryotes, cell division occurs in two major steps: mitosis and cytokinesis.

Explore More

Use this resource to answer the questions that follow.

• http://www.hippocampus.org/Biology → Non-Majors Biology → Search: Cell Division

1. Cell division has how many steps? What are they?2. How do prokaryotic cells divide? How do eukaryotic cells divide?3. Describe the process of binary fission.4. Compare the cells before and after the mitotic division.5. What is cytokinesis?

Review

1. Describe binary fission.2. What is mitosis and what the purpose of mitosis?3. If mitosis works incorrectly what are the possible consequences for an organism?4. Contrast cell division in prokaryotes and eukaryotes. Why are the two types of cell division different?

Vocabulary

• parent cell: a cell that divides to produce two or more daughter cells

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• daughter cells: either of two identical cells that form when a parent cell divides• chromosome: a molecule of DNA• binary fission: the process by which prokaryotic cells divide• mitosis: a multi-phase process in which the nucleus of cells divide. During mitosis, the nuclear membrane

breaks down and later reforms; chromosomes are also sorted and separated to ensure that each daughter cellreceives two sets of chromosomes.

• eukaryote: an organism whose cells contain a nucleus surrounded by a membrane and whose DNA is boundtogether by proteins into chromosomes

• prokaryotes: a single-celled organism that lacks a membrane-bound nucleus, mitochondria, or any othermembrane-bound organelles

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1.2 Embryo Growth and Development

My Learning Goals

• I can explain the importance of cellular specialization as it relates to the characteristics of life.• I can use the process of differentiation in an embryo as an example to describe cellular organization: cells,

tissue, organ, organ system, organism.• I can relate genetic regulation to the process of differentiation.

At one time, did we all really look alike?

We all start as a single cell and soon grow into an embryo. Notice the remarkable details beginning to form. Theeyes, backbone, and limb buds are obvious. Think about the amazing complexity that must be going on inside theembryo, and the tremendous amount of growth and development still to come. So, yes, at one time we all lookedsimilar.

Growth and Development of the Embryo

After implantation occurs, the blastocyst is called an embryo. The embryonic stage lasts through the eighthweek following fertilization. During this time, the embryo grows in size and becomes more complex. It developsspecialized cells and tissues and starts to form most organs.

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Formation of Cell Layers

During the second week after fertilization, cells in the embryo migrate to form three distinct cell layers, called theectoderm, mesoderm, and endoderm. Each layer will soon develop into different types of cells and tissues, asshown in Figure 1.5.

FIGURE 1.5Cell Layers of the Embryo. The migrationof cells into three layers occurs in the 2-week-old embryo. What organs eventu-ally develop from the ectoderm cell layer?Which cell layer develops into muscle tis-sues?

Differentiation of Cells

A zygote is a single cell. How does a single cell develop into many different types of cells? During the thirdweek after fertilization, the embryo begins to undergo cellular differentiation. Differentiation is the process bywhich unspecialized cells become specialized. As illustrated in Figure 1.6, differentiation occurs as certain genesare expressed ("switched on") while other genes are switched off. Because of this process, cells develop uniquestructures and abilities that suit them for their specialized functions.

Organ Formation

After cells differentiate, all the major organs begin to form during the remaining weeks of embryonic development.A few of the developments that occur in the embryo during weeks four through eight are listed in Figure 1.7. As theembryo develops, it also grows in size. By the eighth week of development, the embryo is about 30 millimeters (justover 1 inch) in length. It may also have begun to move.

Summary

• The embryonic stage begins with implantation.• An embryo forms three distinct cell layers, and each layer develops into different types of cells and organs.

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FIGURE 1.6Cellular differentiation occurs in the 3-week-old embryo.

FIGURE 1.7Embryonic Development (Weeks 4–8).Most organs develop in the embryo duringweeks 4 through 8. If the embryo isexposed to toxins during this period, theeffects are likely to be very damaging.Can you explain why? (Note: the draw-ings of the embryos are not to scale.)

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1.2. Embryo Growth and Development www.ck12.org

Explore More

• Guess the Embryo at http://www.pbs.org/wgbh/nova/evolution/guess-embryo.html

Review

1. Explain how the embryo forms specialized cells.2. What organs eventually develop from the ectoderm cell layer?3. Watch Guess the Embryo interactive clip from the Explore More section above. Why do many enbryos appear

so similar during early development?4. If the embryo is exposed to toxins during weeks 4 through 8, the effects are likely to be very damaging. Can

you explain why?

Vocabulary

• blastocyst: an embryo before implantation• embryo: a blastocyst after implantation• zygote: a single cell• differentiation: the process by which unspecialized cells become specialized

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1.3 Stem Cells

My Learning Goals

• I can give give examples of ways stem cells can be used to help organisms maintain homeostasis.

Stem Cells

An unspecialized cell that can divide many times and give rise to different, specialized cells is called a stem cell.Zygotes and embryonic cells are both types of stem cells. The stem cells found in embryos can divide indefinitely,can specialize into any cell type and are called embryonic stem cells. Embryonic stem cells can give rise to anyhuman cell type. Undifferentiated cells that are found within the body and that divide to replace dying cells anddamaged tissues are called adult stem cells. Adult stem cells can divide indefinitely, and generate all the cell typesof the organ from which they originate. They can potentially re-grow the entire organ from just a few cells. A thirdtype of stem cell is found in blood from the umbilical cord of a new-born baby, and the placenta. These “cord bloodstem cells” are considered to be adult stem cells because they cannot generate all body cell types, just different typesof blood cells.

Stem Cells in Medicine

Stem cells are of great interest to researchers because of their ability to divide indefinitely, and to differentiateinto many cell types. Stem cells have many existing or potential therapeutic applications. Such therapies includetreatments for cancer, blood disorders, brain or spinal cord injuries, and blindness.

FIGURE 1.8Human embryonic stem cell colony, whichwas grown in a laboratory on a feederlayer of mouse cells. Embryonic stemcells are totipotent.

Embryonic stem cells, as shown above, are taken from eggs that were fertilized in the laboratory and donated to

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research. They may have the greatest potential because they are totipotent, and thus have the most potential medicalapplications. However, embryonic stem cells harvested from a donated embryo differ from a potential patient’stissue type. Therefore, just as in organ transplantation, there is a risk of a patient’s body rejecting transplantedembryonic stem cells. Some individuals and groups have objections to the harvesting of embryonic stem cells,because harvesting the stem cells involves the destruction of the embryo. Some researchers are looking into methodsto extract embryonic stem cells without destroying the actual embryo. Other researchers have claimed success inharvesting embryonic stem cells from the embryonic fluid that surrounds a growing fetus.

Adult stem cells, including cord blood stem cells, have already been used to treat diseases of the blood such assickle-cell anemia and certain types of cancer. Unlike embryonic stem cells, the use of adult stem cells in researchand therapy is not controversial because the production of adult stem cells does not require the destruction of anembryo. Adult stem cells can be isolated from a tissue sample, such as bone marrow, from a person. Scientists haverecently discovered more sources of adult stem cells in the body. Adult stem cells have been found in body fat, theinside lining of the nose, and in the brain. Some researchers are investigating ways to revert adult stem cells back toa totipotent stage.

Review

1. What is a stem cell?2. What can adult stem cells replace?3. What is the main difference between embryonic and adult stem cells?

Vocabulary

• adult stem cell: a cell that can divide indefinitely and generates all the cell types of the organ from which theyoriginate

• embryonic stem cell: a stem cell found in embryos; can also divide indefinitely and can specialize into anycell type

• differentiate: the process cells undergo to become specialized during development. Genetic expressiondetermines the processes of differentiation.

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1.4 Clones and Transgenic Organisms

My Learning Goals

• I can cite evidence that supports the use of transgenic organisms in human medicine.• I can explain what a transgenic organism is.• I can explain how clones are different from transgenic organisms.

Are cows cloned?

They are, but so are many other animals like sheep and goats. Cloning allows large animals to produce drugs orproteins that are useful in medicine.

Applications of DNA Technology: Animal Cloning

DNA technology has proved very beneficial to humans. Transgenic animals are animals that have incorporated agene from another species into their genome. They are used as experimental models to perform phenotypic testswith genes whose function is unknown or to generate animals that are susceptible to certain compounds or stressesfor testing purposes. Other applications include the production of human hormones, such as insulin. Many timesthese animals are rodents, such as mice or fruit flies (Drosophila melanogaster). Fruit flies are extremely useful asgenetic models to study the effects of genetic changes on development. GloFish are the first genetically modifiedanimal to be sold as a pet and are transgenic zebrafish transfected with a natural fluorescence gene. Watch these fishat http://www.youtube.com/watch?v=6cQLGKH2ojY or in the video below.

MEDIAClick image to the left or use the URL below.URL: http://www.ck12.org/flx/render/embeddedobject/143095

But transgenic animals just have one novel gene. What about an animal with a whole new genome? Could a clone,a genetically exact copy of an organism, be developed using techniques associated with biotechnology? It couldbe argued that human cloning is one of the inevitable outcomes of modern biotechnology. It "simply" involves theremoval of the nucleus from a somatic cell and its placement into an unfertilized egg cell whose nucleus has eitherbeen deactivated or removed. This new cell would mimic the zygote, the first diploid cell of a new organism. Thisnew zygote is allowed to become established, and a few days later is placed into the uterus of a surrogate mother.Theoretically this would result in an individual genetically identical to the donor. Obviously, there are many ethicaland legal issues associated with human cloning, and of course, it is not a "simple" procedure. But animal cloning isarguably a different story.

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Dolly

In February 1997, Ian Wilmut and his colleagues at the Roslin Institute announced the successful cloning of a sheepnamed Dolly from the mammary glands of an adult female ( Figure 1.9) (Nature 385, 810-13, 1997). Dolly wasthe first mammal to be cloned from an adult somatic cell. The cloning of Dolly made it apparent to many thatthe techniques used to produce her could someday be used to clone human beings. This resulted in tremendouscontroversy because of its ethical implications. After cloning was successfully demonstrated by Dolly’s creators,many other large mammals, including horses and bulls, were cloned. Dolly, however, was put down by lethalinjection in February 2003. Prior to her death, Dolly had been suffering from lung cancer and crippling arthritis.Although most sheep like Dolly live to be 11 to 12 years of age, postmortem examination of Dolly seemed toindicate that, other than her cancer and arthritis, she appeared to be quite normal. Dolly was a mother to six lambs,bred through normal methods.

Cloning is now considered a promising tool for preserving endangered species.

FIGURE 1.9Dolly the sheep. Dolly was the first largemammal to be cloned.

In animal cloning, the nucleus from a somatic cell is inserted into an egg cell in which the nucleus has been removed.This process called somatic cell nuclear transfer results in essentially a fertilized egg, a zygote produced in an

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artificial manner. The resulting cell is cultivated and after a few divisions, the developing ball of cells is placed intoa surrogate mother’s uterus where it is allowed to develop into a fetus. The developing fetus will be geneticallyidentical to the donor of the original nucleus ( Figure 1.10).

For an animation of cloning, see this video: https://www.youtube.com/watch?v=q0B9Bn1WW_4

MEDIAClick image to the left or use the URL below.URL: http://www.ck12.org/flx/render/embeddedobject/61285

FIGURE 1.10Reproductive cloning: The nucleus is re-moved from a somatic cell and fused witha denucleated egg cell. The resulting cellmay develop into a colony of cloned cells,which is placed into a surrogate mother.In therapeutic cloning, the resulting cellsare grown in tissue culture; an animalis not produced, but genetically identicalcells are produced.

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Risks of Cloning

Producing a cloned animal is not an insignificant achievement. Most likely it has taken a significant effort bythe group of scientists attempting to make the clone. Rarely do scientists publish or discuss the many cloningexperiments that failed, or even in the successful clones, the issues that tend to arise later, during the animal’sdevelopment to adulthood. Cloning animals shows us what might happen if we try to clone humans.

High Failure Rate

Producing a clone through somatic cell nuclear transfer is not every efficient. The success rate ranges from 0.1percent to 3 percent, which means that for every 1000 tries, only one to 30 clones are made. In other words, thereare 970 to 999 failures in every 1000 attempts. That’s a tremendous failure rate. This failure rate may be due to anumber of circumstances. Keep in mind that somatic cell nuclear transfer is an artificial process. It is not a naturalprocess, and there may still be components of the fertilization and development process that are not well understood.

1. The enucleated egg and the transferred nucleus may not be compatible.2. An egg with a newly transferred nucleus may not begin to divide or develop properly.3. Implantation of the embryo into the surrogate mother might fail.4. The pregnancy itself might fail.

Large Offspring Syndrome

Cloned animals that do survive tend to be much bigger at birth than their natural conceived animals of the samespecies. This is known as "Large Offspring Syndrome." Cloned animals with this syndrome have abnormallylarge organs, which can lead to breathing, blood flow and other associated problems. However this syndrome isunpredictable; it does not always occur, so scientists cannot predict which clones will be affected.

Abnormal Gene Expression

Though surviving clones have identical genomes to their "parent," are they truly clones? Will they express thenecessary genes at the proper times? Gene expression is an extremely complicated and highly regulated cellularprocess (see the Regulation of Gene Expression (Advanced) concepts). One significant issue is to reprogram thetransferred nucleus so that it thinks it is in the zygote, mimicking the natural processes that must be initiated atfertilization, including the expression of the appropriate genes. The cell must be programmed so that the genes thatmust be expressed in that zygote are truly expressed. The nucleus cannot think it is in a differentiated cell, such asthe somatic cell it came from.

See Click and Clone at http://learn.genetics.utah.edu/content/tech/cloning/clickandclone/ to test your knowledge ofsomatic cell nuclear transfer.

Telomeric Differences

As cells divide, their chromosomes get shorter. This is because the telomeres, the DNA sequences at both ends of achromosome, lose material every time the DNA is replicated. The older the animal is, the shorter its telomeres willbe, because of the number of cell cycles the cells have been through This is a natural part of aging. So, what happensto the clone if its transferred nucleus is already fairly old? Will the shortened telomeres affect its development orlifespan? The answer is still unclear. But starting a new organisms with "old" DNA with shortened telomeres isbound to have some effects, at least in some clones. Some cloned animals may be affected, others may not. Dollythe sheep’s chromosomes did have shorter telomere lengths than normal. This means that Dolly’s cells were agingfaster than the cells from a normal sheep.

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Summary

• Transgenic animals are animals that have incorporated a gene from another species into their genome. Theyare used as experimental models to perform phenotypic tests with genes whose function is unknown, or togenerate animals that are susceptible to certain compounds or stresses for testing purposes. Other applicationsinclude the production of human hormones, such as insulin.

• Animal cloning is the generation of genetically identical animals using DNA from a donor animal, not agamete. Dolly, a sheep, was the first mammal to be cloned from an adult somatic cell.

Practice

Use this resource to answer the questions that follow.

• Why Clone? at http://learn.genetics.utah.edu/content/tech/cloning/whyclone/

1. Why is cloning animal models of disease useful in research?2. Why is cloning stem cells for research beneficial?3. What does "Pharming for drug production" refer to?4. How can cloning be used to help endangered species?5. What are some issues associated with cloning?

Review

1. What is the difference between a transgenic animal and a cloned animal?2. Who was Dolly? Why was she important?3. What are the risks of cloning?4. How is cloning useful for medical research and development?5. How are transgenic animals useful for human medical research?

Vocabulary

• clone: A genetically identical copy; may be a gene, a cell or an organism; an organism that is geneticallyidentical to its parent.

• diploid cell: A cell with a full set of chromosomes, half of which came from each parent.• gene expression: The process by which the information in a gene is "decoded" to produce a functional gene

product, such as an RNA molecule or a polypeptide/protein molecule.• haploid cell: A cell with half the normal set of chromosomes. Eggs and sperm are haploid cells prior to

fertilization.• somatic cell: any cell of the body other than egg or sperm cells.• somatic cell nuclear transfer: A technique for creating a embryo clone with a donor nucleus.• telomere: A region of repetitive sequences at each end of a chromosome; protects the end of the chromosome

from deterioration or from fusion with neighboring chromosomes.• transgenic animal: An animal with a foreign gene that has been deliberately inserted into its genome.• zygote: A fertilized egg; the first cell of a new organism.

nsgenecit

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1.5. References www.ck12.org

1.5 References

1. Zachary Wilson. Binary fission of bacteria . CC BY-NC 3.02. Mariana Ruiz Villarreal (LadyofHats) for CK-12 Foundation. Steps of Binary Fission . CC BY-NC 3.03. Zachary Wilson and Mariana Ruiz Villarreal (LadyofHats) (cell images can be found at http://commons.wikimedia.org/wiki/User:LadyofHats/gallery2).

ck 12 foundation .4. Mariana Ruiz Villarreal (LadyofHats) for CK-12 Foundation. Eukaryotic Cell Cycle .5. Zachary Wilson. Embryonic cell layers . CC BY-NC 3.06. Laura Guerin. Embryonic cell differentiation: week3. . CC BY-NC 3.07. CK-12 Foundation, using embryo illustrations copyright lelik759, 2014. Embryonic Development: weeks 4-8

. . Embryo illustrations used under license from Shutterstock.com8. . . Public Domain9. Colin and Sarah Northway. www.flickr.com/photos/46174988@N00/4822043093/ . CC BY 2.0

10. Zachary Wilson. CK-12 Foundation . CC BY-NC 3.0

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