In this article we will discuss about:- 1. Introduction to the Cell Cycle 2. Regulation of Cell Cycle 3. Division of the Nucleus of a Cell 4. Errors in Cell Division.
Introduction to the Cell Cycle:
The higher plants and animals begin their life as a single cell called ovum which is fertilized by a male cell resulting into formation of a zygote. The growth and development of the zygote to form an embryo is affected by a series of divisions. Cells increase in number by dividing into two, after which each daughter cell grows and divides again.
In other words, cells are not dividing always; instead there is a period of rest between two successive divisions which is called as an interphase. Previously interphase was called as the resting phase which is in fact a misnomer, because it is a period of intense biosynthetic activity in which the cell doubles its size and duplicates its chromosome complement. Interphase is immediately followed by the phase of division or M-phase; both of these phases constitute the cell cycle.
Howard and Pelc have divided the entire cell cycle into four successive intervals, viz.:
It immediately follows the phase of division (mitosis or meiosis). It is also called as the pre-DNA synthesis phase. This phase includes the synthesis of the substrates and enzymes necessary for DNA synthesis. Therefore G1-phase is marked by the transcription of various types of RNAs and synthesis of different types of proteins.
The regulation of the duration of cell cycle occurs primarily by arresting it at specific point of G1. The cell in the arrested condition is said to be in the G0-stage. When conditions change and growth is resumed, the cell re-enters the G1-phase.
The G1-period is most variable in length. Depending upon the physiological condition of the cell, it may last days, months or years. For a cell cycle of 24 hours duration, the G-phase takes the first 10 hours.
It is the phase of DNA synthesis. Histones are also synthesized during this phase, and become associated with the newly replicated DNA. During this phase, the euchromatic regions of the genome replicate earlier than the heterochromatic regions. Moreover, in some cells, the G-C rich regions of the genome replicate earlier than A-T rich ones.
It is also called as the post-DNA synthesis phase. It is the period between the end of DNA synthesis and the start of cell division. During this phase all the metabolic activities concerning the growth of cytoplasm and its constituent organelles and macromolecules are performed. Also the factors necessary for chromosome condensation during mitosis are synthesized during this phase. During G2, a cell contains 2-times the amount of DNA present in the original diploid cell.
4. M-Phase or the Phase of Division:
During this phase the cell divides. During cell division, the nucleus divides first (karyokinesis), which is followed by the division of cytoplasm (cytokinesis).
The karyokinesis may occur in following ways:
4. Free nuclear division.
Regulation of Cell Cycle:
For proper continuation of life processes of a eukaryotic cell, it is essential that the different phases of cell cycle are precisely regulated. Any loss of regulation may have serious consequences in the form of chromosomal abnormalities. For exerting an effective control, the cells are allowed to cross these points only if all the necessary conditions are satisfied, otherwise the cell cycle is stopped.
In a eukaryotic cell three check points are proposed-viz.-between G1 and S, between G2 and M-phase and in M-phase itself. At G1/S check-point the damage to DNA and the size of a cell are checked. If these are normal, the cell is allowed to enter S-phase.
At G2/S check point, if DNA has been replicated completely and properly, then only the cell is allowed to enter M-phase.
In M-phase, if spindle fibre is not formed properly and chromosomes are not properly attached to spindle fibre through their centromeres, the cell division stops.
There are two theories to explain the mechanism of regulation of cell cycle:
1. According to domain theory, the cell enters next phase of the cell cycle only if the previous phase is properly completed.
2. However according to clock theory, the cell oscillates between interphase and M-phase due to an inbuilt timer. In such case, inspite of inhibition of one phase of cell cycle, the cell proceeds normally to the next phase. Entry of a cell from one phase to the other is genetically controlled. It is proposed that it is controlled by two groups of enzymes-viz.-cyclin dependent kinases (CdK) and phosphorylating enzymes called cyclins.
The M-phase kinase regulates the entry of ceil into M-phase. It has 2 subunits-one has the catalytic property (catalytic subunit) and the other exerts a regulatory control (regulatory subunit or cyclin). The catalytic subunit is activated by a reversible cycle of phosphorylation and dephosphorylation at the beginning of M-phase. This process is regulated by cyclins; hence they are called cyclin dependent kinases (CdK). The cyclins bind to the M-phase kinase and select the specific proteins which are to be phosphorylated. Similarly the entry of cell into S-phase is regulated by an S-phase kinase.
For their discoveries concerning the regulation of cell cycle Hartwell, Hunt, and Nurse were awarded Nobel Prize in the year 2001. They compared CdK molecules with an engine and the cyclins with a gear box which controls whether the engine will run in the idling state (neutral gear) or will drive the cell forward in the cell cycle.
Division of the Nucleus of a Cell:
This type of nuclear division is affected simply by the elongation of the nucleus followed by its complete division into two halves. The nuclear membrane remains intact throughout the duration of division. Amitosis is usually seen in bacteria, protozoans, algae and fungi.
It is the usual form of nuclear division. It takes place in somatic cells. It was first reported by W. Fleming in 1882.
Mitosis is divided into four successive stages which are called prophase, metaphase, anaphase and telophase.
Chromatin undergoes condensation and takes the form of chromosomes. The chromosomes now begin to contract longitudinally. Due to their contraction the chromosomes become thicker and smoother. The spiral coiling, characteristic of the early prophase chromosomes is lost. This change is often referred to as despiralization.
Towards the end of the prophase, nucleolus and the nuclear membrane disappear and the nucleoplasm is set free, at this stage spindle fibres make their appearance in the cytoplasm. These fibres form the nuclear spindle.
Each chromosome gets attached to a spindle fibre at centromere. Although each chromosome is divided into two chromatids, but the centromere is a single undivided structure at this stage. The chromosomes now quickly become arranged at the equator of the spindle.
During this stage the centromere divides into two. Each half centromere carries one chromatid alongwith it. Due to shortening of the spindle fibers the two chromatids separate from one another and move towards the opposite poles of the spindle, so that the chromosomes frequently assume a V, I, J or L shape. The two groups of chromosomes converge towards the poles, exhibiting a figure of two radiating clusters, which is called the diaster.
Like prophase, telophase also takes a longer time as compared to other phases. As the chromosomes reach the opposite poles, they begin to absorb water again and gradually become thin, hence more difficult to observe. At this stage nuclear membrane and nucleoli make their appearance. Thus two daughter nuclei are produced from one nucleus.
The division of the cytoplasm is known as cytokinesis.
It takes place by any of the following two methods:
(a) By cell-plate formation.
(b) By cleavage of the cytoplasm.
(a) By Cell-Plate Method:
During telophase, droplets of liquid appear in the equatorial region of the spindle. Gradually these droplets unite to form the so-called cell plate. The spindle region along with equatorial plate is called as the phragmoplast. Protoplasmic membranes are then formed by the protoplasm on both the sides of the liquid layer and the cell walls are laid between the protoplasmic membranes.
(b) By Cleavage or Constriction:
This kind of division takes place in many simple plants like fungi and in animal cells. In this case cell division takes place by the formation of a ring like furrow in the plasma membrane. This cleavage deepens until it has cut entirely through the cell. The furrow results in the formation of two plasma membranes.
Importance of Mitosis:
The fundamental importance of mitosis is the equal quantitative and qualitative division of the nuclear material thus the genetic constitution of the nuclei can be maintained. It provides the opportunity for growth and development of the organism by causing an increase in the number of cells. Even the gonads and sex cells also depend on mitosis for the increase in their number after the chromosome number has been halved by meiosis.
Regulation of Mitosis:
R. Hertwig suggested that the cytoplasmic and nuclear coordination regulates mitosis. It is governed by the rate of cellular metabolism which itself is regulated by temperature, nutrients, oxygen, chemicals and other such factors. Cells produce some substances called chalones which inhibit mitosis.
Significance of Mitosis:
1. Chromosomal number in the daughter cells is maintained.
2. Mitosis contributes in growth and development of the organisms.
3. It maintains the DNA and RNA ratio in the cells.
4. It maintains proper size and shape of the cells.
5. Old and decaying cells of body are replaced by new cells produced by mitosis.
3. Meiosis or Reduction Division:
Every plant has a fixed number of chromosomes. If the egg and sperm had the same number of chromosomes as the vegetative cells, the fertilized egg of each generation would contain twice as many chromosomes as the nuclei of the preceding generation. This is prevented by the presence of two successive divisions in the life cycle in which the number of chromosomes is reduced to half that found in the vegetative nuclei. Thus, the number of chromosomes always remains constant by a special type of cell division called meiosis or reduction division. The term meiosis was coined by Farmer and Moore (1905).
The process of meiosis is fundamentally same in all the plants and animals; but certain biologists recognize following three types of meiotic divisions according to their occurrence at different stages of the life cycle of the organisms:
i. Sporogenic or Intermediate Meiosis:
It occurs during sporogenesis in higher plants and results into formation of microspores and megaspores.
ii. Gametic or Terminal Meiosis:
In animals and lower plants, meiosis occurs during gametogenesis and results into formation of gametes (sperm or ova).
iii. Zygotic or Initial Meiosis:
It is seen in lower plants. Here meiosis occurs in the zygote immediately after it is formed by fertilisation.
The cells, in which meiosis takes place, are called meiocytes. The process of meiosis comprises actually the two cell divisions. First division is a reductional division in which the number of chromosomes becomes half and second division is equational division. The reductional division is called as first meiotic division or heterotypic division and the equational division is called as second meiotic division or homotypic division. These two nuclear divisions follow each other in a rapid sequence. As a result of these two divisions, four nuclei are formed but in each daughter cell the number of chromosomes remains half.
First Meiotic Division or Heterotypic Division:
The division takes place in the following stages:
This is the longest stage.
It is divided into a number of sub-stages:
During this stage, chromosomes are extremely thin and can be seen only with difficulty. Only the sex-chromosomes may stand out as compact heteropycnotic bodies.
During this stage, the meiocyte and its nucleus become larger, the chromosomes become more distinct, and their double nature (the two chromatids) is seen in many organisms. They appear as slender threads bearing a series of bead-like structures, called chromomeres.
During zygonema, the chromosomes become shorter and thicker; and the homologous chromosomes start pairing or synapsis. Each pair is called a bivalent. Pairing is highly specific, being chromomere for chromomere. If pairing occurs between non-homologous chromosomes, it is called as pseudosynapsis.
During synapsis the homologous chromosomes remain separated by a space of about 0.15 to 0.20 mm which is occupied by the synaptonemal complex (SC). The SC was discovered by Moses (1956). It is composed of three parallel elements and is supposed to bring the homologous chromosomes together.
In this stage chromosomes become shorter and thicker. Each chromosome in a bivalent, at this stage has two chromatids, thus, a bivalent really consists of four chromatids in pachynema stage, and is called a tetrad. At this stage interchange of chromatid segments (i.e., crossing over) between homologous chromosomes takes place. The nucleolus still persists.
The chromosomes are further thickened and shortened. By now, the intimately paired chromosomes repel each other and begin to separate. The separation starts at centromere and proceeds towards the end. However, the separation is not complete, as the homologous chromosomes are joined together by chiasmata which represent the places of crossing-over. Due to repulsive force between the chromosomes, the chiasmata move towards the ends of chromosomes, this process is called as terminalisation.
This is the final stage of meiotic prophase-l. In this stage chromosomes become very short, thick and coiled. Bivalents are separated off and they move towards periphery of the nucleus. Nuclear membrane disappears. Nucleolus also disappears and spindles are fully formed and well-oriented.
In this stage the bivalents are arranged along the spindle fibres in an equatorial region in such a way that the centromeres of their bivalents are towards the poles.
During this stage, spindle fibres contract due to which bivalents (dyad) move towards the opposite poles of the spindle. Due to the pulling each dyad becomes like an inverted ‘V’. Dyad of a maternal chromosome is completely separated from the dyad of the paternal chromosome. Separation of homologous chromosomes at this stage is called as disjunction.
At the opposite poles, the chromosomes become uncoiled and greatly elongated. Nucleolus and nuclear membrane reappear.
As a result of cytokinesis the cytoplasm is divided into two daughter cells.
This is the interphase stage between the first meiotic and the second meiotic division. If may be of a longer duration or shorter duration.
Second Meiotic Division or Homotypic Division:
The meiotic process is completed only when two Vacuole haploid nuclei divide by a process, which is almost similar to mitosis. This second meiotic division is, sometimes, called meiotic mitosis. As a result of this process four haploid nuclei are formed.
This division takes place in the following stages:
In this stage the nucleolus and nuclear membrane disappear and chromosomes are liberated into the cytoplasm. This stage is followed by the formation of a spindle.
In this stage the chromosomes become arranged along the equatorial plane of the spindle. The centromeres of chromosomes become oriented in the centre and arms extend towards the opposite poles and then centromeres also divide into two each.
In this stage, spindle fibres contract by which a pulling force is exerted on the centromeres. As a result the two sister- chromatids go towards the opposite poles.
In this stage nuclear membrane appears around the chromatids. Nucleolus also appears again.
As result of cytokinesis, the two daughter-nuclei are separated and thus, two daughter cells are formed. Each nucleus has a haploid number of chromosomes. Thus four haploid daughter cells are formed from a single diploid parent cell.
Significance of Meiosis:
1. It helps in production of haploid gametes which maintains the chromosomal number in the offspring after fertilization.
2. It produces new generation.
3. It leads to variations in generations caused by crossing overs which occur during meiosis.
Errors in Cell Division:
During cell division if some error occurs at any stage or phase of division then that causes abnormalities in an individual. These abnormalities can be due to structural or numerical changes in the chromosomes. These changes can be in the autosomes or the sex chromosomes.
Abnormal Human Karyotype/Syndromes:
Chromosomes are the structures which carry the genetic information in the form of DNA. These are highly dynamic structures having proper regulatory organization. Chromosomal confirmation plays important role in expression of gene while the topology of the chromosome also plays important role. A slight change in the topology of chromosome can affect the action of gene.
Structural Aberrations in Chromosomes:
When the structure of a chromosome is altered it is called chromosomal aberrations.
It is of four main types:
When a portion of the chromosome is missing or deleted then it is called deleted.
Deletion is a genetic aberration in which a part of a chromosome or a sequence of DNA is missing. Deletion is the loss of genetic material. Any number of nucleotides can be deleted, from a single base to an entire piece of chromosome. It can be caused by errors in cross-over during meiosis. Deletion of a number of base pairs that is not evenly divisible by three will lead to a frame- shift mutation, causing all of the codons occurring after the deletion to be read incorrectly during translation, producing a severely altered and potentially non-functional protein.
Duplication is the opposite of a deletion. Duplications arise from an event termed unequal crossing over that occurs during meiosis between misaligned homologous chromosomes. The chance of this happening is a function of the degree of sharing of repetitive elements between two chromosomes. The product of this recombination is duplication at the site of the exchange and a reciprocal deletion.
When a portion of one chromosome is transferred to another non-homologous chromosome it is called translocation. Translocation is chromosome abnormality caused by rearrangement of parts between non-homologous chromosomes. When an even exchange of material with no genetic information extra or missing and ideally full functionality occurs it is called balanced translocation. When the exchange of chromosome material is unequal resulting in extra or missing genes it is called unbalanced translocation.
An inversion is a chromosome rearrangement in which segment of a chromosome is reversed end to end i.e., when a segment of chromosomes breaks but later rejoins after rotating by 180°, it results in inversion.
An inversion occurs when a single chromosome undergoes breakage and rearrangement within itself. Inversions are of two types, viz., Paracentric inversions do not include the centromere and both breaks occur in one arm of the chromosome. Pericentric inversions include the centromere and there is a break point in each arm.
A. Abnormalities due to Structural Changes in Chromosomes:
1. Cat Cry Syndrome (Cri-Du-Chat Syndrome):
It is due to deletion of short arm (p-arm) of the 5th chromosome; affected child has small epiglottis and larynx, therefore cries like a kitten; face becomes moon like, head is small and the child shows physical and mental retardation.
Malignant tumor of eye, is due to the deletion of part of 13th chromosome.
3. Deletion of long arm of 18th chromosome produces symptoms like skeletal and ophthalmic abnormalities along with profound mental retardation and facial alterations.
4. Granulocytic Leukemia:
It occurs due to translocation of long arm (q-arm) of 22nd chromosome to the 9th chromosome, causing increased proliferation and accumulation of the granulocytes. The deleted 22nd chromosome is called Philadelphia chromosome.
Sometimes the chromosomes of a chromosome pair are unable to separate at the first meiotic division. This leads to the formation of a gamete containing all the chromosomes of that chromosomal pair, while the other gamete does not contain any chromosome part.
This phenomenon is called non disjunction.
Non-disjunction is of two types:
(a) Primary Non-Disjunction:
C.B. Bridges during his experiments reported unexpected conditions in the inheritance of the sex linked characters. While crossing red-eyed male with white eyed female drosophila he observed red-eyed males and white-eyed females in F1 generation (contrary to the expected condition of white-eyed males and red-eyed females).
This condition was explained on the basis of non-disjunction of X-chromosome in the female drosophila. According to him the white-eyed females carry two X-chromosomes which were inherited from the mother, therefore, the colour of eyes was white. On the other hand red-eyed males could not get the X-chromosome from the mother due to non-disjunction. They received X-chromosome only from the father.
(b) Secondary Non-Disjunction:
When Bridges crossed the white-eyed females of the F1 generations (carrying XXY-chromosome due to primary non-disjunction) with red-eyed normal male the offsprings had 96% of red-eyed females and 4% of white-eyed females. At meiosis, the XXY will disjoin to form X & XY in a normal condition, but the secondary non disjunction results into XX & Y gamete. This gave rise to XXY white-eyed females and XY red-eyed males.
B. Abnormalities due to Numerical Changes in Chromosomes:
1. Due to Aneuploidy of Sex Chromosomes:
(a) Turner’s Syndrome:
Monosomy of X-chromosome (44 + XO). Phenotypically such females are short stature, having streak gonads, multiple pigmented nervi (birth marks) and webbed neck.
(b) Klinefelter’s Syndrome:
It is the Trisomy of sex chromosomes (44 + XXY). Trisomies show gigas effect for certain genes. These are sterile males with gynaecomastia. This syndrome includes even XXXY and XXXXY – type males showing even greater degree of sterility.
(c) XXX Syndrome/Super Male (Jacob’s) Syndrome:
Although such males are said to have criminal records, but several workers have recently criticized this view.
(d) XYY Syndrome:
Super female syndrome, short statured, sterile females.
2. Due to Aneuploidy of Autosomes:
Commonly it involves the chromosomes of groups D, E and G.
(a) Patau’s Syndrome:
Trisome of 13th chromosome. The affected children show mental retardation, defective eyes as well as cardiac disorders.
(b) Edward’s Syndrome:
Trisomy of 18th chromosome. The affected children show anomalies of fingers, achodroplasia, complex digital prints, heart defects, low set ears and small mouth. They die before one year of age.
(c) Down’s Syndrome/Mongolism/Mongoloid Idiocy:
It is trisomy of 21st chromosome (due to non-disjunction during oogenesis). It is the most familiar trisomy of man. It was described by Langdon Down (1866) of England for the first time.
The symptoms of Down’s syndrome are as follows:
(a) Short broad hands with simian type palmar crease.
(b) Short stature.
(c) Hyperflexibility of joints.
(d) Mental retardation.
(e) Broad head with round face.
(f) Open mouth with large tongue.
The complexity of behavioural traits of any animal develops under joint, tightly entwined effects of heredity and environment.
Behaviour genetics is thus concerned with the effects of genotype on behaviour and with the role that genetic differences play in the determination of behavioural differences in a population.
Uniparental Disomy (UPD):
The presence of two copies of a chromosome or part of a chromosome from only one parent and not from the other parent is called uniparental disomy or UPD.
In humans uniparental disomy was first discovered in 1988 in a child suffering from a disease called cystic fibrosis and short height. It was discovered by Spence and coworkers who proved that the child had received two copies of chromosome number 7 with a mutant CF gene (CF gene) from her mother but none from the father.
After this, many other disorders are also reported due to uniparental disomy. Although the frequency of occurrence of uniparental disomy is not clear, yet it has been estimated that about one out of 500 affected individuals is due to maternal uniparental disomy.
A normal chromosome is linear in shape which may have two sister chromatids at some stage of cell cycle. If the topology changes from linear to circular form it may affect the sequence of events or actions.
The change from linear to circular form results in the formation of ring chromosome. It results in various abnormalities such as tumors etc.
Ring chromosomes can be formed by following ways:
(a) Ring chromosome may be formed due to breakage in the chromosome arms and fusion of the proximal ends resulting into loss of genetic material at distal ends.
(b) It may also be formed by telomeric disjunction resulting into fusion of relative chromosome ends. Here the genetic materials at distal ends are lost causing either minimum effect or they remain intact.
Cells (and their owners) are said to be polyploid if they contain more than two haploid (n) sets of chromosomes; i.e., their chromosome number is some multiple of n greater than the 2n content of diploid cells. For example, triploid (3n) and tetraploid (4n) cells are polyploid.
Polyploidy in Plants:
Polyploidy is very common is plants, especially in angiosperms. From 30% to 70% of today’s angiosperms are thought to be polyploid. Species of coffee plant with 22, 44, 66 and 88 chromosomes are known. This suggests that the ancestral condition was a plant with a haploid (n) number of 11 and a diploid (2n) number of 22, from which evolved the different polyploid descendants.
The present day wheat, with its 42 chromosomes, is a hexaploid (6n) of its ancestral plant with its haploid number (n) equal to 7.
Polyploid plants not only have larger cells but the plants themselves are often larger. This has led to the deliberate creation of polyploid varieties of such plants as watermelons, marigolds and snapdragons.
Polyploidy has occurred often in the evolution of plants. The process can begin if diploid (2n) gametes are formed.
These can arise in at least two ways:
(a) The gametes may be formed by mitosis instead of meiosis.
(b) Plants, in contrast to animals, form germ cells (sperm and eggs) from somatic tissues. If the chromosome content of a precursor somatic cell has accidentally doubled (e.g., as a result of passing through S phase of the cell cycle without following up with mitosis and cytokinesis), then gametes containing 2n chromosomes are formed.
Polyploidy also occurs naturally in certain plant tissues. As the endosperm (3n) develops in corn kernels (Zea mays), its cells undergo successive rounds (as many as 5) of endoreplication producing nuclei that range as high as 96n.
Polyploidy can be of following two types:
Autopolyploids are polyploids with multiple chromosome sets derived from a single species. Autopolyploids can arise from a spontaneous, naturally occurring genome doubling, like the potato. Others might form following fusion of diploid (2n) gametes. Bananas and apples can be found as autotriploids. Autopolyploid plants typically display polysomic inheritance and are therefore often infertile and propagated clonally perfect.
Allopolyploids are polyploids with chromosomes derived from different species. Precisely it is the result of doubling of chromosome number in an F1 hybrid. Triticale is an example of an allopolyploid, having six chromosome sets, allohexaploid, four from wheat (Triticum turgidum) and two from rye (Secale cereale). Amphidiploid is another word for an allopolyploid.