Important Point: Uncontrolled cell division = cancer.Statistically the probability of any one of us being here is so small that you would think the mere possibility of existence would keep us all in a contented dazzlement of surprise.
—Lewis Thomas (1913–1993)
Topics in This Chapter
In the last quarter century there has been a revolution in our comprehension of how cells grow and divide. Results from experiments on embryos, yeast, and cultured mammalian cells have unified disparate viewpoints into a single set of principles of normal cellular reproduction in plants, animals, and bacteria (Murray & Hunt 1993).
Approximately 25 million cell divisions occur in an adult human every second. The cells of our hair follicles, skin, bone marrow, and the lining of our GI tracts are turning over, dividing constantly. Why? That is, why must cells divide? Isn’t growth a characteristic of all living things? And since this is the case, why can’t cells just continue to grow along with everything else? Cells must divide because total size of a cell is limited. This is because, as cell size increases, the surface area to volume ratio decreases (i.e., it becomes harder for materials to diffuse to the center of the cell). Moreover, larger cells would need more DNA to make proteins than one nucleus can contain. Accordingly, multicellular organisms grow by cell division. Cell growth and division are usually controlled by the organism for reproduction (in bacteria and amoeba) to allow an organism to grow and develop, and to repair or replace damaged or dead cells.
Important Point: Uncontrolled cell division = cancer.
The cell cycle is an ordered set of events. These events or phases, diagrammed below, culminate in cell growth and division into 2 daughter cells—nondividing cells are not considered to be in the cell cycle.
INTERPHASE
Period of cell growth between cell divisions. Includes phases 1–3:
Phase 1: G1 (Gap 1)
Cell growth and development
Phase 2: S (Synthesis)
DNA replication takes place (result is 2 copies of
each DNA molecule at end of phase)
Phase 3: G2 (Gap 2)
Organelles and other materials necessary
for cell division are synthesized
MITOSIS
Phase 4: M (Mitosis)
Period of nuclear division
According to the National Center for Biotechnology Information (2006), for most unicellular organisms, reproduction is a simple matter of cell duplication, also known as replication. But for multicellular organisms, cell replication and reproduction are 2 separate processes. Multicellular organisms replace damaged or worn out cells through a replication process called mitosis, the division of a eukaryotic cell nucleus to produce 2 identical daughter nuclei. To reproduce, eukaryotes must first create special cells called gametes—eggs and sperm—that then fuse to form the beginning of a new organism. Gametes are but one of the many unique cell types that multicellular organisms need to function as a complete organism.
Most unicellular organisms create their next generation by replicating all of their parts and then splitting into 2 cells, a type of asexual reproduction called binary fission. This process spawns not just 2 new cells, but also 2 new organisms. Multicellular organisms replicate new cells in much the same way. For example, we produce new skin cells and liver cells by replicating the DNA found in that cell through mitosis. Yet, producing a whole new organism requires sexual reproduction, at least for most multi-cellular organisms. In the first step, specialized cells called gametes—eggs and sperm—are created through a process called meiosis. Meiosis serves to reduce the chromosome number for that particular organism by half. In the second step, the sperm and egg join to make a single cell, which restores the chromosome number. This joined cell then divides and differentiates into different cell types that eventually form an entire functioning organism (NIH 2004).
The process of mitosis and meiosis are diagrammed below. Before studying the mitosis/meiosis breakdowns, review the definitions of key terms:
• Centriole—a cylindrical cytoplasmic organelle located just outside the nucleus of animal cells and the cells of some lower plants; associated with the spindle during mitosis and meiosis.
• Centromere—a special region on a chromosome from which kinetochore microtubules radiate during mitosis or meiosis.
• Chromatin—the mixture of DNA and protein (mostly histones in the form of nucleosome cores) that comprises eukaryotic nuclear chromosomes.
• Chromosomes—a filamentous structure in the cell nucleus, mitochondria, and chloroplasts along which the genes are located. The chromosome characteristics of humans include:
• A diploid set (in which cells contain 2 sets of chromosomes, 1 maternal and 1 paternal); abbreviated 2n; 2n = 46
• Autosomes (chromosomes that are not sex chromosomes); these are homologous chromosomes, 1 from each parent (22 sets of 2)
• Sex hormones (humans have 1 set of 2):
1. Female—sex chromosomes are homologous (XX)
2. Male—sex hormones are nonhomologous (XY)
• Histones—one of a class of basic proteins serving as structural elements of eukaryotic chromosomes.
• Kinetochore—placed on either side of the centromere to which the spindle fibers are attached during cell division.
• Nucleosome—a complex consisting of several histone proteins, which together form a “spool,” and chromosomal DNA, which is wrapped around the spool.
• Spindle—a microtubular structure with which the chromosomes are associated in mitosis and meiosis.
• Tetrad—a homologous pair of double-stranded chromosomes, attached at the centromeres.
Mitosis is the period of nuclear division. Every time a cell divides, it must ensure that its DNA is shared between the 2 daughter cells. Mitosis is the process of “divvying up” the genome between the daughter cells:
• Interphase
• Technically not a part of mitosis, but it is included in the cell cycle
• Cell is in a resting phase, performing cell functions
• DNA replicates (copies)
• Organelles double in number, to prepare for division
• Prophase
• Chromatin coils into short thick structures (known as chromosomes) and become visible
• Centrioles separate and move to opposite sides of the nucleus (animal cells only)
• Paired chromosomes (chromatids) attach to spindle fibers at centromere (spot where chromatids are attached to each other)
• Nuclear membrane and nucleolus break down and disappear
• Metaphase
• Chromosomes line up across the equator, or center of the cell, pulled by the spindle fibers
• Anaphase
• Centromeres split, sister chromatids separate, are drawn to opposite poles of the cell by the spindle fibers
• Telophase
• Chromosomes begin to uncoil
• Nuclear envelopes form around 2 daughter nuclei
• Nucleolus forms in each nucleus
• Spindle fibers break apart
• Cytoplasm begins to divide (cytokinesis)
• Cytokinesis (final step)
• Cell’s cytoplasm divides in 2 ways:
Animal cells—cell membrane moves in towards the center of cell, cell pinched into 2 nearly equal parts
Plant cells—cell plate forms midway between the 2 nuclei
• Cell wall forms on either side of cell plate
Important Point: Cytokinesis happens differently in plant cells because it isn’t easy to pinch off that tough cell wall.
Meiosis is a specialized type of cell division that occurs during the formation of gametes. That is, meiosis involves reproduction. Although meiosis may seem much more complicated than mitosis, it is really just 2 cell divisions in sequence. Each of these sequences maintains strong similarities to mitosis. Meiosis differs in that this single replication is followed by 2 consecutive divisions—Meiosis I and Meiosis II; meiosis produces 4 daughter cells and each has half the number of chromosomes as the original cell. Dean A. Adkins of the website “Biology Notes” describes the stages of meiosis:
• Interphase I
• Chromosomes replicate as in mitosis
• Meiosis I
• Reduces chromosome number by one half
• Prophase I
• Chromosomes condense
• Synapse occurs; during this process homologous chromosomes come together as pairs. Each homologous pair of replicated chromosome of 2 chromatids complex as 4 intertwined chromatids—tetrad. Nonsister chromatids are linked by X-shaped chiasmata, sites where homologous strand exchange or crossing-over occurs
• Other event similar to prophase of mitosis
• Metaphase I
• Tetrads are aligned on the metaphase plate
• Each homologue attached to kinetochore microtubules
• Anaphase I
• Chromosomes are moved toward poles by spindle apparatus
• Sister chromatids remain attached at their centromeres
• Differs from mitosis in that chromatids do not separate at this time
• Telophase I and Cytokinesis
• Chromosomes reach poles
• Each pole now has a haploid set of chromosomes still composed of 2 sister chromatids attached at the centromere
• Cytokinesis occurs; some cells pause but others immediately prepare for Meiosis II
• Prophase II
• Nuclear envelope and nucleoli disperse
• Spindle apparatus forms
• Metaphase II
• Chromosomes align singly on metaphase plate
• Anaphase II
• Centromeres of sister chromatids separate
• Sister chromatids of each pair (now individual chromosomes) move toward opposite poles of the cell
• Telophase and Cytokinesis
• Nuclei form
• Cytokinesis occurs, producing 4 haploid daughter cells (Adkins 2006)
Meiosis is reduction division. Cells produced by mitosis have same number of chromosomes as the original cell, but cells produced by meiosis have half the number of chromosomes as the original cell. Meiosis creates genetic diversity. Mitosis produces 2 cells identical to parent cell whereas meiosis produces 4 cells genetically different from parent cell and from each other. Meiosis is 2 successive nuclear divisions.
When Gregor Mendel, an Austrian monk, began his hybridization experiments with pea plants in 1856, knowledge of how heredity works was limited. For example, if black furred animals mated with white furred animals, it was expected that all resulting progeny would be gray (a color intermediate between black and white). They found, of course, that this is often not the case. The correct explanation of inherited traits was provided by Mendel (and later by others) through his study of peas.
Before discussing Mendelian genetics it is important to understand the context of his times as well as how his work fits into the modern science of genetics. Key genetic terms include:
• Allele—an alternate form of a gene. Usually there are 2 alleles for every gene, sometimes as many as 3 or 4.
• Autosome—a chromosome that is not a sex chromosome.
• Chromosome—a structure in the cell nucleus that carries the genes and is capable of reproduction through cell division.
• Dihybrid cross—tracking the inheritance of 2 traits between 2 individuals.
• Dominant trait—term applied to the trait (allele) that is expressed irregardless of the second allele.
• Gene—unit of inheritance that usually is directly responsible for one trait or character.
• Genotype—the allelic composition of an organism.
• Heterozygous—when the 2 alleles are different, in such cases the dominant allele is expressed.
• Homozygous—when the 2 alleles are the same.
• Monohybrid cross—tracking the inheritance pattern of a single trait between 2 individuals.
• Phenotype—expressed traits of an individual.
• Punnett squares—probability diagram illustrating the possible offspring of a mating.
• Recessive trait—term applied to a trait that is only expressed when the second allele is the same.
• Test cross—a mating between an individual with an unknown genotype for a specific trait with an individual who is homozygous recessive for the same trait.
• True-breeding—sexually reproduced organisms with inherited traits(s) identical to parents.
Important Point: A gene is a discrete unit of heredity located on chromosomes that consists of DNA. An allele is an alternate form of a specific gene. (e.g., eye color gene vs. blue eye allele)
In 1856, Mendel developed the fundamental principles that would become the modern science of genetics. Mendel was successful in his studies because he used a quantitative approach; counted offspring traits over several generations; used probabilities to interpret the results; studied one trait at a time; and used the common garden pea (Pisum sativum). The common garden pea is easy to cultivate and has a short generation time. Mendel examined 7 traits in the pea plant: flower color, flower position, seed color, seed shape, pod color, pod shape, and stem length. Mendel reasoned that each characteristic only occurs in 2 contrasting forms—dominant and recessive.
Mendel chose the common garden pea because he knew that pollen from a pea plant can fertilize the female eggs of the same plant. Self-fertilization provides strict control over mating. That is, seeds produced by self-fertilization inherit only traits present in the plant that bore them. With continued experimentation, Mendel learned how to prevent self-fertilization and performed many cross-pollination experiments.
A hybrid is the product of parents that are true-breeding for distinctly different traits. A monohybrid cross is a cross involving a single trait. Mendel tracked traits through 2 generations:
P generation—parental
F1 generation—first offspring
F2 generation—second generation obtained from cross-breeding F1 generation
The results of Mendel’s experiments contradicted those of previous theories. He found that F1 resembled parents and F2 showed ¼ plants resembled one parent, ¾ resembled the other.
Important Point: Mendel found that phenotypes (genetically determined appearance) were in a 3:1 ratio (Grobner 2004).
Mendel used dihybrid crosses to explain how 2 pairs of genes are distributed in the gametes. Mendel crossed tall peas that had green pods and short peas that had yellow pods. All the offspring of the F1 generation had the same phenotype—tall pea plants with green pods.
When he allowed the hybrid pea plant to self-fertilize, he found a phenotypic relationship of 9:3:3:1 among the plants in the F2 generation (Grobner 2004).
During his era, Mendel did not know about genes and meiosis. However, his Theory of Segregation still stands. During several experiments, Mendel developed a 4-part hypothesis: (1) he suggested that alternative forms of inherited units are responsible for variations in traits; (2) for each trait, an individual inherits 2 alleles, one from each parent; (3) if the alleles differ, one is expressed (dominant) and the other is masked (recessive); and (4) the 2 alleles segregate during gamete production.
As a result of his dihybrid crosses, Mendel thought that inheritance of a pair of factors for one trait is independent of the simultaneous inheritance for another trait. Today, we know that this theory can be explained by meiosis—factors assort independently.
1. Incomplete dominance
• Offspring show traits intermediate between 2 parental phenotypes
• Red-flowered and white-flowered four o’clocks produce pink flowers
• Not a blending—parental phenotypes reappear in F2
2. Codominance
• Both alleles of a gene are expressed
• Both genes produce an effective allele
• Human blood types—AB individuals’ red blood cells (RBCs) express both A and B antigens
3. Multiple alleles
• More than 2 alleles for a given locus
• Only 2 alleles inherited
• ABO blood system
• Alleles A, B, and O
• Blood types A, B, AB, and O
4. Epistasis (masking of the effects of one gene by the action of another)
• Absence of expected phenotype due to masking on one gene pair by another
• Homozygous recessive at one locus masks the effect of a dominant allele at another
• Albino animals—inherit allelic pair (aa) preventing melanin production
• Mammal coat color
5. Pleiotropy (a genotype with multiple phenotypic effects)
• Single gene exerts on many aspects of an individual’s phenotype
6. Polygenic inheritance
• A trait is controlled by several alleic pairs at different loci
• Gene alleles can be contributing or noncontributing
• Contributing alleles have additive effect resulting in variation
• Subject to environmental effects producing intermediate phenotypes
7. Environmental effects on the phenotype (the outward appearance of an organism)
• Both genotype and environment affect phenotype
• Relative importance of each varies
• Calculated as heritabilities
• Intelligence has environmental component
Mendel published his research in 1865. However, his unique, groundbreaking notion of genes was not appreciated by naturalists of his time. Thus, Mendel’s work lay fallow until 1900, when scientists independently confirmed his results. These confirmations, based on the study of the cell and chromosomal behavior, gave Mendel’s abstract work the physical context—the teeth—it needed. For example, modern genetics explain Mendel’s observations in the following ways:
• Each trait is controlled by 2 alleles
• Alternative gene forms at the same gene locus on homologous chromosomes:
Dominant allele—masks expressions of recessive allele
Recessive allele—only expressed when both alleles are recessive
• Gene locus
• Specific location of a particular gene on homologous chromosomes
• Mendel’s true-breeding plants were homozygous for the traits he studied:
Homozygous—contains the same alleles at both loci
Heterozygous—contain different alleles at the 2 loci
• Homozygous dominant:
Possess 2 dominant alleles for a trait
• Homozygous recessive
Possess 2 recessive alleles for a trait Trait is expressed
• In heterozygous organisms, the recessive trait is not expressed
• Genotype vs. phenotype
• Genotype:
Refers to the genetic makeup of an individual
Lists the alleles present
• Phenotype:
Refers to the physical appearance of the individual
Represents gene expression
• Punnett square
• Provides a simple method to determine the probable offspring of a genetic cross
• Used to show all the possible outcomes of a genetic cross and to determine the probability of a particular outcome.
• In the Punnett square shown above, the XX chromosomes represent a female and XY represents a male. From the Punnett square it can be seen that scientists can figure out the percentage of an offspring being a boy or girl with specific traits.
• Test crosses
• Allow for the verification of genotypes in an individual
• Dominant individual may be heterozygous or homozygous dominant
• Use a homozygous recessive individual as the test
• Recessive phenotypes (½) in the offspring indicate heterozygous individual
There are 44 autosomes and 2 sex chromosomes in the human male and female genome, for a total of 46. There may be only 2 sex chromosomes, but they are critically important. They determine the gender of the individual. Females have XX chromosomes and males have XY chromosomes. The Y chromosome is much smaller than the X.
NIH (2006) points out that DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA).
The information in DNA is stored as a code made up of 4 chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billion bases, and more than 99% of those bases are the same in all people. The order, or sequence, of these bases determines the information available for building and maintaining an organism, similar to the way in which letters of the alphabet appear in a certain order to form words and sentences.
DNA bases pair up with each other—A with T and C with G—to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and a phosphate are called a nucleotide. Nucleotides are arranged in 2 long strands that form a spiral called a double helix. The structure of the double helix is somewhat like a ladder, with the base pairs forming the ladder’s rungs and the sugar and phosphate molecules forming the vertical sidepieces of the ladder.
An important property of DNA is that is can replicate, or make copies of itself. Each strand of DNA in the double helix can serve as a pattern for duplicating the sequence of bases. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell (NIH 2006).
1. What kind(s) of cell division do eukaryotes do?
2. To which part of a chromosome do spindle fibers attach?
3. What are the stages of the cell cycle?
4. What are the stages of mitosis?
5. How many cells are present at the end of mitosis?
6. What are the stages and phases of meiosis?
7. What types of chromosomes form a tetrad?
8. How many cells are present at the end of meiosis?
9. What makes meiosis different from mitosis?
10. Define and distinguish between the terms “gene” and allele.”
11. Define and distinguish between the terms “genotype” and “phenotype.”
12. Define the terms “dominant” and “recessive.”
Grobner, M.A. 2004. Biology 1010: Genetics Lecture. Stanislaus, CA: California State University.
John, B., et al. 1990. Meiosis. London: Cambridge University Press.
Mitosis/Meiosis DVD. 2004. New York: Educational Video Network, Inc.
Murray, A.W., and T. Hunt, 1993. Cell Cycle: An Introduction. New York: W.H. Freeman.
NCBI. 2006. A Science Primer. National Center for Biotechnology Information. Accessed July 6, 2006, at www.ncbi.nim.nih.gov.
NIH. 2004. A Science Primer: Making New Cells. Washington, DC: Department of Health and Human Services, National Institutes of Health.
NIH. 2006. What Is DNA. Washington, DC: National Institutes of Health. Accessed August 19, 2006, at http://ghr.nlm.nih.gov/handbook/basics/dna.
Parker, G., and W.A. Reynolds. 1979. Mitosis and Meiosis. Illinois: Dearborn Trade Publishing.
Rieder, C.L., et al. 1998. Mitosis and Meiosis: Methods in Cell Biology, Vol. 6. New York: Academic Press.
Thomas, L. 1995. The Medusa and the Snail: More Notes of a Biology Watcher. New York: Penguin Books.
