Anatomy and Chemistry Basics
The Cell
Cell division consists of two phases, nuclear division followed by cytokinesis. Nuclear division divides the genetic material in the nucleus, while cytokinesis divides the cytoplasm. There are two kinds of nuclear division—mitosis and meiosis. Mitosis divides the nucleus so that both daughter cells are genetically identical. In contrast, meiosis is a reduction division, producing daughter cells that contain half the genetic information of the parent cell.
The first step in either mitosis or meiosis begins with the condensation of the genetic material, chromatin, into tightly coiled bodies, the chromosomes. Each chromosome is made of two identical halves called sister chromatids, which are joined at the centromere. Each chromatid consists of a single, tightly coiled molecule of DNA. Somatic cells (all body cells except eggs and sperm) are diploid cells because each cell contains two copies of every chromosome. A pair of such chromosomes is called a homologous pair. In a homologous pair of chromosomes, one homologue originates from the maternal parent, the other from the paternal parent. There are 46 chromosomes, 23 homologous pairs, consisting of a total of 92 chromatids.
When a cell is not dividing, the chromatin is enclosed within a clearly defined nuclear envelope, one or more nucleoli are visible within the nucleus, and two centrosomes (each containing two centrioles) lie adjacent to one another outside the nuclear envelope. These features are characteristic of interphase, the nondividing but metabolically active period of the cell cycle (Figure
1 ). When cell division begins, these features change, as described in the following sections.
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Mitosis
There are four phases in
mitosis (adjective, mitotic): prophase, metaphase, anaphase, and telophase (Figure
2 ).
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During prophase, the nucleoli disappear, the chromatin condenses into chromosomes, the nuclear envelope breaks down, and the mitotic spindle is assembled. The development of the mitotic spindle begins as the centrosomes move apart to opposite ends (poles) of the nucleus. As they move apart, microtubules develop from each centrosome, increasing in length by the addition of tubulin units. Microtubules from each centrosome connect to specialized regions in the centromere called kinetochores. Microtubules tug on the kinetochores, moving the chromosomes back and forth, toward one pole, then the other. Within the spindle, there are also microtubules that overlap at the center of the spindle and do not attach to the chromosomes.
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Metaphase begins when the chromosomes are distributed across the metaphase plate, a plane lying between the two poles of the spindle. Metaphase ends when the microtubules, still attached to the kinetochores, pull each chromosome apart into two chromatids. Each chromatid is complete with a centromere and kinetochores. Once separated from its sister chromatid, each chromatid is called a chromosome. (To count the number of chromosomes at any one time, count the number of centromeres.)
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Anaphase begins after the chromosomes are separated into chromatids. During anaphase, the microtubules connected to the chromatids (now chromosomes) shorten, effectively pulling the chromosomes to opposite poles. Overlapping microtubules originating from opposite centrosomes but not attached to chromosomes interact to push the poles farther apart. At the end of anaphase, each pole has a complete set of chromosomes, the same number of chromosomes as the original cell. (Since it consists of only one chromatid, each chromosome contains only a single copy of the DNA molecule.)
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Telophase concludes the nuclear division. During this phase, a nuclear envelope develops around each pole, forming two nuclei. The chromosomes within each of these nuclei disperse into chromatin, and the nuclei reappear. Simultaneously, cytokinesis occurs, dividing the cytoplasm into two cells. Microfilaments form a ring inside the plasma membrane between the two newly forming nuclei. As the microfilaments shorten, they act like purse strings to pull the plasma membrane into the center, dividing the cell into two daughter cells. The groove that forms as the purse strings are tightened is called a cleavage furrow.
Once mitosis is completed and interphase beings, the cell begins a period of growth. Growth begins during the first phase, called G1, and continues through the S and G2 phases. Also during the S phase the second DNA molecule for each chromosome is synthesized. As a result of this DNA replication, each chromosome gains a second chromatid. During the G2 period of growth, materials for the next mitotic division are prepared. The time span from one cell division through G1, S, and G2 is called a cell cycle (Figure 1 ).
A cell that begins mitosis in the diploid state—that is, with two copies of every chromosome—will end mitosis with two copies of every chromosome. However, each of these chromosomes will consist of only one chromatid, or one DNA molecule. During interphase, the second DNA molecule is replicated from the first, so that when the next mitotic division begins, each chromosome will, again, consist of two chromatids.
Meiosis
Meiosis (adjective, meiotic) is very similar to mitosis. The major distinction is that meiosis consists of two groups of divisions, meiosis I and meiosis II (Figure
3 ). In meiosis I, homologous chromosomes pair at the metaphase plate and then migrate to opposite poles. In meiosis II, chromosomes spread across the metaphase plate, and sister chromatids separate and migrate to opposite poles. Thus, meiosis II is analogous to mitosis. A summary of each meiotic stage follows.
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Prophase I begins like prophase of mitosis. The nucleolus disappears, chromatin condenses into chromosomes, the nuclear envelope breaks down, and the spindle apparatus develops. Once the chromosomes are condensed, however, their behavior differs from mitosis. During prophase I, homologous chromosomes pair, a process called synapsis. These pairs of homologous chromosomes are called tetrads (a group of four chromatids) or bivalents. During synapsis, corresponding regions form close associations called chiasmata (singular, chiasma) along nonsister chromatids. Chiasmata are sites where genetic material is exchanged between nonsister homologous chromatids, a process called crossing over. The result contributes to a mixing of genetic material from both parents, a process called genetic recombination.
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At metaphase I, homologous pairs of chromosomes are spread across the metaphase plate. Microtubules extending from one pole are attached to kinetochores of one member of each homologous pair. Microtubules from the other pole are connected to the second member of each homologous pair.
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Anaphase I begins when homologues within tetrads uncouple as they are pulled to opposite poles.
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In telophase I, the chromosomes have reached their respective poles, and a nuclear membrane develops around them. Note that each pole will form a new nucleus that will have half the number of chromosomes, but each chromosome will contain two chromatids. Since daughter nuclei will have half the number of chromosomes, cells that they eventually form will be haploid.
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Cytokinesis occurs forming two daughter cells. A brief interphase may follow, but no replication of chromosomes occurs. Instead, part II of meiosis begins in both daughter nuclei.
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In prophase II, the nuclear envelope disappears, and the spindle develops. There are no chiasmata and no crossing over of genetic material as in prophase I.
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In metaphase II, the chromosomes align singly on the metaphase plate (not in tetrads as in metaphase I). Single alignment of chromosomes is exactly what happens in mitosis—except now there is only half the number of chromosomes.
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Anaphase II begins as each chromosome is pulled apart into two chromatids by the microtubules of the spindle apparatus. The chromatids (now chromosomes) migrate to their respective poles. Again, this is exactly what happens in mitosis—except now there is only half the number of chromosomes.
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In telophase II, the nuclear envelope reappears at each pole and cytokinesis occurs. The end result of meiosis is four haploid cells. Each cell contains half the number of chromosomes, and each chromosome consists of only one chromatid.
Meiosis ends with four haploid daughter cells, each with half the number of chromosomes (one chromosome from each homologous pair). These are gametes —that is, eggs and sperm. The fusing of an egg and sperm, fertilization(syngamy), gives rise to a diploid cell, the zygote . The single-celled zygote then divides by mitosis to produce a multicellular embryo fetus, and after nine months, a newborn infant. Note that one copy of each chromosome pair in the zygote originates from one parent, and the second copy from the other parent. Thus, a pair of homologous chromosomes in the diploid zygote represents both maternal and paternal heritage.
DNA replication
During the S phase of interphase, a second chromatid is assembled. The second chromatid contains the exact same DNA found in the first chromatid. The copying process, called DNA replication, involves separating (“unzipping”) the DNA molecule into two strands, each of which serves as a template to assemble a new, complementary strand. The result is two identical double-stranded molecules of DNA that consist of a single strand of old DNA (the template strand) and a single strand of new, replicated DNA (the complementary strand).
Two difficulties must be resolved during replication. First, DNA polymerase, the enzyme that regulates the attachment of new nucleotides to the growing complement strand of DNA, can perform this task in only one direction. The two strands that make up the double helix, however, are oriented in opposite directions (anti-parallel). On one strand, the DNA polymerase can operate continuously toward the replication fork as the DNA double helix is unzipped. The new DNA strand generated in this manner is called the leading complementary strand. Since the nucleotides of the second template strand are oriented in the opposite direction, DNA polymerase must operate away from the replication fork. As a result, replication of the second strand occurs in short segments. As the replication fork advances, the DNA polymerase must repeatedly return to the replication fork to begin replication of short segments of DNA. The enzyme DNA ligase connects these short segments of DNA generating the lagging complementary strand.
The second difficulty that is resolved during replication is that DNA polymerase cannot itself initiate replication. Instead, the enzyme RNA primase initiates each replication using RNA (not DNA) nucleotides. After a short RNA nucleotide segment is generated, DNA polymerase takes over with DNA nucleotides. The initial RNA nucleotides are later replaced with the appropriate DNA nucleotides.
Following are the details of DNA replication. Numbers correspond to events illustrated in Figure
4 .
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The enzyme helicase unwinds the DNA helix, producing Y-shaped replication fork.
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RNA primase initiates DNA replication by producing short segments of RNA nucleotides called RNA primers. (See 2A and 2B in Figure 4 .)
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DNA polymerase attaches to the RNA primase and begins adding DNA nucleotides to the complement strand. (In Figure 4 , the RNA primase is present only on the lagging strand.)
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The leading complementary strand is assembled continuously as the double-helix of DNA uncoils.
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The lagging complementary strand is assembled in short segments, which are subsequently joined by DNA ligase. (See 5A, 5B, and 5C in Figure 4 .)
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The RNA primers are replaced by DNA nucleotides.
Mutations
The replication process of DNA is extremely accurate. However, errors occur when nucleotide bases between DNA strands are occasionally paired incorrectly. In addition, errors in DNA molecules may arise as a result of exposure to radiation (such as ultraviolet or x-ray) or various reactive chemicals. When errors occur, repair mechanisms are available to make corrections.
If a DNA error is not repaired, it becomes a mutation. A mutation is any sequence of nucleotides in a DNA molecule that does not exactly match the original DNA molecule from which it was copied. Mutations include an incorrect nucleotide (substitution), a missing nucleotide (deletion), or an addition nucleotide not present in the original DNA molecule (insertion). When an insertion mutation occurs, it causes all subsequent nucleotides to be displaced one position, producing a frameshift mutation. Radiation or chemicals that cause mutations are called mutagens. Carcinogens are mutagens that activate uncontrolled cell growth (cancer).
Protein synthesis
The DNA in chromosomes contains genetic instructions that regulate development, growth, and the metabolic activities of cells. The DNA instructions determine whether a cell will be that of a pea plant, a human, or some other organism, as well as establish specific characteristics of the cell in that organism. For example, the DNA in a cell may establish that it is a human cell. If during development, it becomes a cell in the iris of any eye, the DNA will direct other information appropriate for its location in the organism, such as the production of brown, blue, or other pigmentation. DNA controls the cell in this manner because it contains codes for polypeptides. Many polypeptides are enzymes that regulate chemical reactions and influence the resulting characteristics of the cell. Thus, from the molecular viewpoint, traits are the end products of metabolic processes regulated by enzymes. A gene is defined as the DNA segment that codes for a particular enzyme or other polypeptide (one-gene-one-polypeptide hypothesis).
The process that describes how enzymes and other proteins are made from DNA is called protein synthesis. There are three steps in protein synthesis—transcription, RNA processing, and translation. In transcription, DNA molecules are used as a template to create RNA. After transcription, RNA processing modifies the RNA molecule with deletions and additions. In translation, the processed RNA molecules are used to assemble amino acids into a polypeptide.
There are three kinds of RNA molecules produced during transcription, as follows.
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Messenger RNA (mRNA) is a single strand of RNA that provides the template used for sequencing amino acids into a polypeptide. A triplet group of three adjacent nucleotides on the mRNA, called a codon, codes for one specific amino acid. Since there are 64 possible ways that four nucleotides can be arranged in triplet combinations (4 × 4 × 4 = 64), there are 64 possible codons. The genetic code is a table of information that provides “decoding” for each codon—that is, it identifies the amino acid specified by each of the possible 64 codon combinations. For example, the codon composed of the three nucleotides cytosine-guanine-adenine (CGA) codes for the amino acid arginine.
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Transfer RNA (tRNA) is a short RNA molecule (consisting of about 80 nucleotides) that is used for transporting amino acids to their proper places on the mRNA template. Interactions among various parts of the tRNA molecule result in base-pairings between nucleotides, folding the tRNA in such a way that it forms a three-dimensional molecule. (In two dimensions, a tRNA resembles the three leaflets of a clover leaf.) One end of the tRNA attaches to an amino acid. Another portion of the tRNA, specified by a triplet combination of nucleotides, is the anticodon. During translation, the anticodon of the tRNA base pairs with the codon of the mRNA.
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Ribosomal RNA (rRNA) molecules are the building blocks of ribosomes. The nucleolus is an assemblage of DNA actively being transcribed into rRNA. Within the nucleolus, various proteins imported from the cytosol are assembled with rRNA to form large and small ribosome subunits. Together, the two subunits form a ribosome, which coordinates the activities of the mRNA and tRNA during translation. Ribosomes have three binding sites—one for the mRNA, one for the tRNA that carries a growing polypeptide chain, and one for a second tRNA that delivers the next amino acid that will be inserted into the growing polypeptide chain.
Here are the details of transcription, RNA processing, and protein synthesis (also see Figures
5 and
6 ):
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During transcription, the RNA polymerase attaches to promoter regions on the DNA and beings to unzip the DNA into two strands. (See 1 in Figure 5 .)
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As the RNA polymerase unzips the DNA, it assembles new nucleotides using one strand of the DNA as a template. In contrast to the process of DNA replication, the new nucleotides are RNA nucleotides, and only one DNA strand is transcribed . (See 2 in Figure 5 .)
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Transcription continues until the RNA polymerase reaches a special sequence of nucleotides that serves as a termination point. The RNA polymerase and the newly created RNA molecule are released. This newly created RNA molecule may be mRNA, tRNA, or rRNA (depending on which DNA segment is transcribed). (See 3 in Figure 5 .)
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During RNA processing, newly crated mRNA molecules undergo two kinds of alterations. In the first modification, noncoding intervening sequences called introns are removed, leaving only exons, sequences that express a code for a polypeptide. A second modification adds two special sequences—a 5-inch cap to one end of the mRNA and a poly-A tail to the other end. (See 4A, 4B, and 4C in Figure 5 .)
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The mRNA, tRNA, and ribosomal subunits are transported across the nuclear envelope and into the cytoplasm. In the cytoplasm, amino acids attach to one end of the tRNAs. (See 5A, 5B, and 5C in Figure 6 .)
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Translation begins when the small and large ribosomal subunits attach to one end of the mRNA. Also, a tRNA (with anitcodon UAC) carrying the amino acid methonine attaches to the mRNA (at the “start” codon AUG) within the ribosome. (See 6 in Figure 6 .)
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A second tRNA, also bearing an amino acid, arrives and fills a second tRNA position. The codon on the mRNA determines which tRNA (and thus, which amino acid) fills the second position. (Step 7 in Figure 6 shows an incoming tRNA approaching a yet to be vacated position.)
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The amino acid of the first tRNA attaches to the amino acid of the second tRNA, forming a pair of amino acids. Then, the first tRNA is released. The ribosome moves over one codon position, thereby putting the second tRNA in the first position and vacating the second position. (Step 8 in Figure 6 shows this process after several tRNAs have delivered amino acids.)
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A new tRNA (with its amino acid) fills the vacant position. Now, the two amino acids being held by the tRNA in the first position are transferred to the amino acid of the newly arrived tRNA, forming a polypeptide chain of three amino acids. Again, the tRNA in the first position is released, the ribosome moves over one codon position, and the second tRNA position is vacant.
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The process continues, as new tRNAs bring more amino acids. As each new tRNA arrives, the polypeptide chain is elongated by one new amino acid, growing in sequence and length as dictated by the codons on the mRNA. (See 9 in Figure 6 .) Eventually, a “stop” codon is encountered, and the ribosome subunits and polypeptide are released.
Once the polypeptide is released, interactions among the amino acids give it its special three-dimensional shape. Subsequent processing by the endoplasmic reticulum or a Golgi body may make final modifications before the protein functions as a structural element or an enzyme.
