Cell Reproduction - Mitosis and Meiosis

Cell Reproduction - Mitosis and Meiosis

One of the statements of the cell theory is that "All cells come from preexisting cells by a process of cell reproduction, or cell division".

We know that all cells of an individual have exactly the same DNA in their chromosomes and that each species has a fixed chromosome number, a number that does not change from generation to generation. We have recently studied the process of DNA duplication. Now we can see how cells reproduce and distribute the duplicated DNA equally into new cells formed.

To ensure that chromosomes and DNA remain the same in new cells, the following must take place when cells divide:

We must form two new cells from the original cell.
Since each cell must have all of the genetic material for the organism, it is crucial to have a mechanism that exactly duplicates the DNA from the original cell and distributes the copied DNA equally to the new cells. We have just seen how DNA duplication is accomplished. The distribution of DNA into new nuclei during cell division is called mitosis.
We must also separate the cytoplasm, and critical organelles, such as mitochondria and chloroplasts, of the original cell into the new cells formed so that the new cells can survive, grow and function. The separation of cytoplasm into new cells is called cytokinesis.

Mitotic cell division is the process by which all cells of a multicellular organism are formed. Cell division is also responsible for repair and replacement of cells and tissues during one's lifetime, and for asexual reproduction, a means of making more individuals common in protists, fungi, many plants and some animals.

In our discussion of cell reproduction, we shall focus on the processes of cell reproduction in eukaryotic organisms. The process of cell division in prokaryotic organisms has similarities, but the single molecule of DNA and absence of a nucleus in the prokaryotic cell account for a number of differences in the "mechanics" of the process. Your text covers some of the specifics of prokaryotic cell division, a process called binary fission.

In addition, in sexually reproducing organisms, a variation of cell reproduction, called meiosis, occurs at one stage in the organism's life cycle (to form gametes in animals, or to start the gamete producing stage in plants). We will discuss the process of meiosis later.

The processes, or events, of cell division can be related to the normal lifetime of a cell. For our convenience, these events are divided into "stages" of a cell's cell cycle.

Cell division is but one process of the cell cycle. The cell cycle starts when a cell is formed and continues until it divides (or dies). Some cells never divide; others are specialized for division (especially in plants, where virtually all cell division occurs in specialized tissue called meristem). Cell division is a brief part of the life cycle; most of the life of a cell is spent in normal activities of growth and maintenance.

The cell cycle involves the following:

Interphase
The period of time when a cell undergoes its normal activities, including

Growth

₁

DNA Duplication

Preparation for Division

₂

₁

₀

chromatin

Cell Division (or cell reproduction), which includes
Mitosis, with

Prophase
Metaphase
Anaphase
Telophase
Cytokinesis

Cell reproduction in eukaryotes must therefore involve 3 events:

DNA Duplication
- Process of duplicating the genetic material of the nucleus
- This occurs during Interphase , when growth and/or normal metabolic activities take place.
Mitosis
- Process of distributing the duplicated DNA equally to the two new nuclei.
Cytokinesis
- Process of separating the cytoplasm contents

The events of the cell cycle are carefully regulated using signal pathways at checkpoints in the cycle. Cells that stay in G₀ for example, never receive the appropriate signal at the G₁ checkpoint to proceed into DNA synthesis.

Before we actually talk about processes of cell division, we must first discuss some terms (and other stuff) that deal with the genetic material of the cell.

DNA

The genetic molecule

Chromatin

All of the DNA of the nucleus with its associated proteins. During the normal metabolic activities of the cell, or Interphase, the collective DNA, or chromatin, appears dense and granular.

Chromosome

The individual pieces of DNA with their associated proteins. During normal cell activities, (Interphase) the chromosomes are stretched out so thinly, they can not be distinguished (hence, the use of the term chromatin for the aggregate).

Chromosomes are visible only during the process of cell division.

Each species has a set number of chromosomes.

Chromosomes are self-duplicating, or self-replicating

Chromosome Terms before and after Duplication

An unduplicated chromosome is one chromosome. A chromosome more or less consists of two arms that extend from a centralized region called the centromere.

When a chromosome duplicates, it becomes one duplicated chromosome, and the two copies remain attached to each other. Note it is still one chromosome.

The two exact copies of the duplicated chromosome, which remain attached at the centromere region, are called "sister" chromatids. They are identical to each other. (Remember this; it is essential!)

At the centromere region of the duplicated chromosome, there are structures (made of protein and DNA) called kinetochores. The kinetochores attach to microtubules of the spindle during mitosis.

After the identical sister chromatids are separated during mitosis, each (called a "daughter" chromosome now) becomes a single unduplicated chromosome again.

Rule to remember: A chromatid must be attached to its identical chromatid and the two sister chromatids comprise one duplicated chromosome. "Sister" chromatids are not two chromosomes. They are one duplicated chromosome that consists of two identical chromatids. The only time you can use the word chromatid is when you have the two identical chromatids attached to each other.

And now, just to complicate life:
If we look at the chromosomes of most eukaryotic organisms carefully, it can be seen that for each individual chromosome, a second chromosome can be found that physically matches it in length and shape. Closer inspection of the DNA shows that the matching chromosomes have very similar, but not identical DNA which carries equivalent genetic information, or genes. These matching chromosomes, with their similar DNA, form the basis of the variation we see in the genetic traits of living organisms.

This also means that chromosomes can be distinguished as matching pairs, and we call these matching chromosomes homologous chromosome pairs, or homologues. A display of homologous chromosome pairs is called a karyotype. The human karyotype has 23 pairs of chromosomes.

Cells that contain pairs of homologous chromosomes are called diploid. When a cell has chromosome pairs, we can refer to the diploid number of chromosomes, again meaning that each chromosome has a match, or homologue in that cell. For humans, the diploid number of chromosomes is 46. These 46 chromosomes are comprised of 23 homologous pairs of chromosomes.

"Ploid" as a general term also means a "set", so we can also say that a diploid cell has two sets of chromosomes, or two of each kind of chromosome. (It's possible to have more than 2 chromosomes of each kind. Polyploids are quite common in agriculture as a result of plant breeding. Polyploids are less common in animals.)

Remember: "Sister" Chromatids are not pairs; they are the two identical parts of one duplicated chromosome. You must make this distinction! The pairs are the homologous chromosomes.

Meiosis and Reducing Chromosome Number
To introduce something we will also study, all organisms that have sexual reproduction must undergo a meiosis cell division at some point in the life history (see later) that reduces the chromosome number of the cell by one-half. Such cells are called haploid, having half as many chromosomes as the diploid cells of the organism.

In animals, the only haploid cells of the organism are the gametes. Animal gametes then join together to form a zygote, or fertilized egg, the first cell of the next generation. This fusion restores the diploid number. Meiosis occurs at different times of the life history of plants, fungi and many protists. We shall discuss meiosis in detail a bit later.

For the process of mitosis and cell division, we need not be concerned about homologous chromosomes. Each chromosome during mitosis functions independently. Just keep this information in your mind for later.

Back to Mitosis and the Eukaryotic Cell Cycle.
Recall that the cell cycle consists of two major phases: Interphase, when the cell undergoes growth, normal activities and prepares for division when it undergoes DNA duplication, and cell division. Cell division consists of mitosis, where the duplicated chromosomes are distributed equally (one chromatid of each duplicated chromosome to each of the new nuclei) and cytokinesis, where the cytoplasm or the original cell is separated into new cells.

Again, Interphase is divided into the respective activities:

Growth (called G₁ or Gap in the cell cycle)
- Normal growth and cell activities
DNA Duplication (called S for synthesis in the cell cycle)
- DNA duplication forming the duplicated chromosomes
- This event is triggered by the individual cell signals in the G₁ phase. Once started this process cannot be reversed; the cell is committed to divide.
Preparation for Division (called G₂)
- Molecules needed to do cell division are manufactured in preparation for mitosis and cytokinesis.
- Cells can continue to grow and do their normal cell activities as well.
- A G₂ checkpoint controls whether or not the cell will go into mitosis.

The Stages of Mitosis
Mitosis is a continuum. Humans have decided to separate the process into stages for the convenience of our discussion. And you might note that some humans even separate the stages into sub-stages and intermediate stages.

Properly, mitosis refers to events of nuclear division. Cytoplasmic division occurs during the accompanying cytokinesis

Prophase

Chromosome Condensation

Duplicated chromosomes start to condense from the diffuse chromatin and become visible as threadlike structures. Chromosomes continue to condense and become thicker as prophase progresses.
The nucleolus region (an aggregation of chromosome bits and concentrated RNA and protein) of the nucleus will start to disappear.
The duplicated chromosomes are firmly attached at their centromeres throughout this condensation and coiling.

Microtubule Organization

Microtubules initiate spindle formation and determine the poles of the cell. The spindle apparatus will extend from the poles of the cell to the center of the cell surrounding the nuclear region and to the opposite pole of the cell.
Some microtubules from each pole of the cell attach to a protein structure, called the kinetochore, located in the centromere region of each duplicated chromosome.
Other microtubules overlap each other from poles through the equator region of the cell.
In animal cells, clusters of microtubules form around the centrioles, which replicated during interphase, and migrate to the respective poles of the dividing cell. These regions are called the spindle poles, or asters. Centrioles are not essential to this process. Cells which lack centrioles still form the spindle complex.

Nuclear membrane

The nuclear membrane degrades in later prophase into small vesicles, which can be used to synthesis new nuclear membrane material in the new cells.

prometaphase.

Metaphase

The spindle apparatus moves the chromosomes to the equator of the cell, aligning the centromeres of each duplicated chromosome along the equator.
Chromosomes are moved by a combination of pulling and pushing of spindle microtubules.
The length of the spindle microtubules is regulated by the kinetochores to facilitate the alignment of centromeres at the equator.
This alignment of chromosomes along the equator plane of the cell is often called the metaphase plate.

Anaphase

Centromeres of each duplicated chromosome split and separate to start anaphase. You can't actually see this; the separating chromosomes are the first visual sign of anaphase.
Kinetochore motor proteins pull their chromosomes along the spindle microtubules from the equator to the poles of the cells. The microtublues disintegrate becoming shorter.
The overlapping polar microtubules lengthen moving the poles of the cell further apart, and, in animal cells elongating the cell.
Since sister chromatids are identical, each of the two clusters of chromosomes being pulled to the two poles of the cell has one copy of each original chromosome. As the chromosomes are pulled toward the poles, they begin to lengthen out.

Telophase

Chromosomes stretch back out and become indistinct as chromatin
Membrane vesicles form new nuclear membranes around each group of chromosomes (at the two poles)
The spindle microtubules disperse and the spindle apparatus disappears
New nucleoli form

Cytokinesis: Separation of the Cytoplasmic Contents
Speaking precisely, mitosis describes events of chromosomes and nuclei. Most cells accompany mitosis with cytokinesis, the separation of the cytoplasm of the original cell into two new cells. This is not always the case. Some organisms (including many fungi and algae) are "multinucleate", they just have one cell body with many nuclei. Some animal tissues are also multinucleate.

Cytokinesis coincides with the events of telophase or occurs immediately after, so that at the completion of mitosis, the original cell is separated into two cells, each with a nucleus and DNA identical to that of the original cell. Although the end result of cytokinesis is always two new cells, the mechanism of separation is different in plants and animals, so we shall discuss them separately.

Cytokinesis in Animal Cells
The cells of animals lack cell walls. Cytokinesis in animal cells is started with the formation of a cleavage furrow, a depression or pinching in of the plasma membrane.

This is caused by a ring of microfilaments (the contractile ring), composed of the protein, actin, which forms across the middle of the cell after the chromatids are separated in anaphase. This ring contracts, pinching the membrane toward the center of the cell, which eventually pinches the cell in two. The additional membrane surface needed is supplied by membrane made during interphase.

Cytokinesis in Plant Cells
Each cell of a plant is surrounded by a cell wall, which is quite rigid. Plant cells can not form a cleavage furrow. Instead, plant cells are separated by the cell plate formation.

Cell plate formation involves making a cross wall at the equator of the original cell. Golgi vesicles containing wall material fuse along microtubules forming a disk-like structure which is called the phragmoplast or cell plate. As cellulose and other fibers are deposited, the cell plate is formed creating a boundary and new cell wall between the two new cells.

Membrane material from the original cell fuses to each side of the cell plate forming new cell membranes on the dividing sides of the original cell.

When and Where does Mitosis Occur?
Growth
All growth (increase in numbers of cells) in individual organisms takes place by mitosis, from the fertilized egg (zygote) to death...

Replacement
Many cells are routinely replaced in organisms. This replacement of cells is done by mitosis. For examples, we replace the cells which line our digestive tract every 1 - 3 days.

Repair and Maintenance
Mitosis is used for repair and replacement of damaged cells or tissues, whenever possible. This includes regeneration of lost parts for some organisms.

Non-Sexual (Asexual) Reproduction
Mitosis is used for all asexual reproduction or propagation. This is especially common in plants, fungi and protists. In fact, the world's largest organism is a fungus that spreads over 2200 acres in Oregon. Asexual reproduction produces offspring genetically identical to the original parent. Animals rarely reproduce non-sexually. When this does occur, the offspring are genetically identical to the parent, as would be expected of any mitosis.

Cloning, a method of producing genetically identical offspring, uses mitosis, precisely because mitosis duplicates the DNA exactly. Cloning is quite easy to do with many plants, since they are easily propagated non-sexually anyway. We find huge groves of Aspen trees, all of which are root clones. Many of the agricultural products originate from cloned individuals, such as navel oranges.

Tissue culture is also a popular way of cloning plants. Most cells of plants retain the ability to "dedifferentiate" and become embryonic-like. Most animal cells, once specialized (or differentiated), cannot do so.

In many animals, cloning takes on a different meaning. The new organism takes a nucleus from the "parent", but the nucleus is injected into an egg cell from that species, from which the egg cell nucleus has been removed. The "clone" is then implanted into a surrogate mother for development. Dolly, the sheep, is our most famous mammal clone to date. Dolly is essentially genetically identical to the individual from whom the nucleus was removed, but the cytoplasm of the donor egg cell has some influence on early development and especially in mitochondria.

The successful "cloning" of mammals has resulted in a flurry of research, and speculation about cloning humans. This is one of the biological issues that has serious ethical consequences. One of the reasons each of us should learn as much as possible about biology is to make informed decisions about the ethical applications of research.

Sexual Life Cycles and Meiosis
Since we started our discussions about DNA and cell reproduction, we have discussed how DNA interacts in the expression of genetic information to direct the synthesis of proteins, and how DNA replicates prior to cell reproduction. We have just finished looking at the process of mitosis, a process that produces cells genetically identical to the original cell.

We have briefly mentioned meiosis, the process used to reduce the chromosome number and distribute chromosomes sometime in the life cycle of an organism prior to the process of sexual reproduction.

We have discussed that chromosomes occur as homologous pairs, which are physically matched. The homologous pairs of chromosomes are also matched genetically; each homologous chromosome has a gene for a specific trait, so that a diploid organism typically has two genes, or two pieces of DNA for each genetic characteristic, one on each of its homologues.

By the way, as we shall discuss later, the genes on homologous chromosomes do not have to be identical (although they can be). We know for example, that you can inherit either brown eyes or blue eyes; a tongue that curls, or one that cannot curl. The alternative forms that genes can take are called alleles. Inheritance looks at how these pieces of DNA interact to produce the traits expressed in individuals.

Meiosis is necessary to ensure that each new generation has the same chromosome number as the preceding generation, but meiosis has a second, most important function for living organisms: maintaining genetic variation. Each time meiosis occurs, followed by, at some point, sexual reproduction, the new individual is genetically different from either parent. Because meiosis is involved with genetic variation and is needed for sexual reproduction, we need to mention a few things about genetic inheritance and sexual reproduction to better understand why meiosis is so important.

During meiosis there is some shifting and recombining of alleles so that gene combinations always occur in the gametes that are different from the parent.

In sexual reproduction, each parent typically has two "genes" (or more correctly, two alleles of a gene) for each characteristic (one on each of the homologous chromosomes). Each parent passes one of these genes (but not both) and one of each of its homologous chromosomes to the offspring by meiosis and fertilization. The fertilized egg (zygote) will then have two genes for each trait, one from each parent. It's important to note that each individual will have a paternal set of chromosomes and a maternal set of chromosomes. Each homologous pair of chromosomes has one paternal and one maternal origin.

Since parents are not genetically identical, their gametes will have different combinations of genes. Each egg and each sperm (or each spore) is genetically different from the parent's DNA (having only half as much). The offspring (children) formed by sexual reproduction will have genetic variation, important for the long-term response of species to their environment. Such variations among offspring lead to physical, behavioral and physiological differences. These differences may be more or less useful in the surroundings of that organism, and are subject to the agents of selection. This variation is an important basis for evolutionary change, which will be discussed later.

Not all organisms reproduce sexually. Many organisms have both sexual and non-sexual means of propagation, or increasing the numbers of individuals. Asexual reproduction, which uses mitosis, can be a good strategy in an environment that is constant, if a species is well-suited to those conditions. Dandelions, for example, rarely reproduce sexually; their seeds develop without fertilization. They are highly successful in the suburban lawn. And suburban lawn owners spend a lot of time making sure that their lawn looks just the same year after year, carefully applying water and nutrients several times each growing season. This is perfect for dandelions. Sexual reproduction might introduce variation that could result in a dandelion less fit for the suburban lawn. Without sexual reproduction, however, there can be little genetic variation, and species without genetic variation cope poorly over time with changing environments.

We should mention that meiosis is something that takes place at just one point in any sexually reproducing organism's life cycle. In animals, meiosis generally occurs to form gametes: sperm or eggs. In many other types of organisms, meiosis occurs at some other point in the life cycle, and the products of meiosis may be spores, (as in plants) or the first cells of the next generation (for most protists and most fungi). At some point however, all organisms that sexually reproduce will make haploid gametes.

Homologous chromosome pairs are essential to how meiosis works. In meiosis the homologous chromosomes literally pair up prior to the reduction of chromosome number. In meiosis, one of each type of chromosome (one of each homologous pair) is distributed to each meiotic product, so that the meiotic products have half as many chromosomes as the "parent" cell. This is the crucial difference between mitosis and meiosis, and explains why we can reduce chromosome number and still have all of the genetic information needed to form a new organism. The homologous pairs of chromosomes in diploid organisms do not interact during mitosis (each chromosome is on its own).

After meiosis, the meiotic products have a haploid (half the parental) number of chromosomes, and no pairs of homologous chromosomes. Haploid also refers to the cell when there is just one of each kind of chromosome, or the "n" number of chromosomes. (Diploid is the 2n number of chromosomes.)

The diploid number of chromosomes will be restored when two gametes (egg and sperm) unite in sexual fertilization.

The Process of Meiosis - Details
As mentioned, during meiosis, homologous chromosomes line up or literally pair with each other. Meiosis reduces the chromosome number by one-half in a way that assures that the gametes will get one of each pair of homologues. The equal distribution of chromosomes is critical to the process of meiosis. The products of meiosis (such as the gametes in animals) have no pairs of chromosomes and are haploid, since they have half the chromosomes as the parent cell. When fertilization occurs, the diploid number is restored, along with the matching chromosomes.

To achieve the reduction in chromosome number and appropriate distribution of chromosomes, meiosis requires two divisions. At the completion of the second division, four cells will typically be produced. The stages of meiosis resemble those of mitosis; the differences occur in the matching or pairing of the homologous chromosomes, which occurs during the first division prophase.

The Meiosis Stages (Or how we break up a continuous process into chunks)

Pre-Meiotic Interphase
The DNA of the cell* that will do meiosis replicates. (DNA replication must precede any cell division.) The identical sister chromatids of each replicated chromosome are attached at their centromeres and have their kinetochores.

* Again, cells that do meiosis are restricted to sex organs, such as the ovary and the testis of animals; or anther and ovule of "higher" plants; or sporangia of "lower" plants. The sex organs are diploid, just as is the rest of the organism. Only the products of meiosis (gametes or gamete-producing structures) are haploid.

Some organisms have a haploid life cycle; most of their assimilative life is spent with cells that are haploid. Meiosis immediately follows the formation of the zygote. The haploid cells produced are the first cells of the next generation, which grow by mitosis to become adults.

Meiosis I
Prophase I

Homologous chromosomes pair up at the start of prophase I in a process called synapsis. This uses proteins along the chromosomes to join the homologues together. The homologues literally join at several points (called chiasmata). All four chromatids of the homologous pair are aligned together.
This arrangement allows for a process of genetic importance to occur. The intertwined chromatids of the homologous chromosomes break at one or more places and exchange equivalent bits of DNA with each other. This exchange is called crossing over. This occurs between the non-sister chromatids, and is mediated by enzymes. If the alleles of the homologues were different forms of the genes, than recombination occurs. The sister chromatids now have some genetic variation; they are no longer identical.
After crossing over takes place, the still-joined homologues pull apart slightly, although the chromosomes are still attached at the chiasmata.
All things that we normally think of taking place in a prophase also occur in prophase I of meiosis, including attaching spindle fibers to each chromosome of the attached homologous pairs.

Metaphase I

Homologous pairs of chromosomes, still synapsed, are moved to the equator by the spindle complex.
The alignment is random; some maternal chromosomes will orient facing one pole along the equator; others face the opposite pole. Spindle fibers just attach to homologous chromosomes as they find them from the respective poles of the cell.

Anaphase I

The homologous chromosomes are separated from each other and pulled toward opposite poles during Anaphase I.
Replicated chromosomes are not affected during Anaphase I. The sister chromatids are still tightly bound to each other by their centromeres.
The chromosome number is officially reduced at this time because each nucleus that will form around the set of chromosomes at each pole will have half the number of chromosomes as the pre-meiotic cell. All of the chromosomes will still be replicated. No sister chromatids have separated.
No homologous chromosome pairs are present at the end of Anaphase I. Each cluster of chromosomes at the respective poles of the cell will have one of each type of homologous chromosome. It is the pairing and separation of homologs which is the key to reducing chromosome number while maintaining all of the genetic information.

Telophase I and Interkinesis

Typically two new nuclei are formed, each with one set of the homologous chromosomes
Cytokinesis will form two cells. Each chromosome is still replicated (which occurred in pre-meiotic interphase), and essentially the cells are just preparing for the second division. Some cells do not bother with cytokinesis here, or even form new nuclear envelopes, which will just have to be degraded during meiosis II, anyway.

Meiosis II
Prophase II

New spindle apparatus is formed in each of the two cells from telophase I
The still-replicated chromosomes stretch out and recondense
Spindle fibers attach to the kinetochores of each of the sister chromatids, one from each pole.
Nuclear membranes degrade

Metaphase Ii

The replicated chromosomes are aligned along the equator by the spindle complex

Anaphase II

Centromeres of sister chromatids are detached from each other.
The now non-replicated chromosomes are pulled to the poles of the cells.

Telophase II and Cytokinesis

Each new nucleus formed has half the number of the original chromosomes but each nucleus has one of each type of homologous chromosome.
A total of four new cells will be produced.

Genetic Importance of Meiosis
To conclude our discussion of meiosis, and to initiate further discussion of genetics and inheritance let us recall that the genetic traits we inherit are in the form of gene alternatives, called alleles. These alleles are located on the homologous chromosomes.

The zygote receives different parental combinations of homologs from the egg and sperm. How these alternatives gets expressed is the study of inheritance.

Meiosis plays the following roles in inheritance:

Recombination or crossing-over between non-sister chromatids during synapsis (Prophase I) produces gametes with greater variation.
The independent assortment (or alignment) of maternal and paternal chromosomes at Metaphase I when homologous chromosomes are lined up on the cell equator results in greater genetic variation.
The fusion of genetically different gametes results in new genetic combinations for each generation.
Meiosis provides a mechanism to preserve chromosome number from generation to generation.

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