Cell Division 1


The mechanism of cell division both mitosis and meiosis

And Cell Cycle regulation




Cells of all organisms undergo cell division at one of the other stages of their development.  In many unicellular forms, cell division is an important mode of multiplication.  But in multi-cellular organisms, cell division is absolutely required for growth.  Reproductive elements like gametes are the other important products of cell division.


Types Cell divisions:  Organisms exhibit two types of cell divisions.  This is based on the pattern of distribution of parental chromosomes to the daughter cells.  They are Mitosis and Meiosis; however in prokaryotic organisms like bacteria and blue green algae, where there is no organized nucleus, the cell division is equational and it is called Amitosis, for the mitotic apparatus and such complicated chromosomal movements are absent.  Whatever may be the types, all cell divisions involve two important events viz, Nuclear division called Karyokinesis and cytoplasmic division called Cytokinesis.



Amitosis is also referred to as Binary fission or direct division.  This type of division is employed by lower prokaryotes, not only for multiplication of cells but also for reproduction.  In this context, a bacterial cell has been taken as an example of describe the process.


E.coli cells;www.unc.edu      


At the time of bacterial cell division, the circular DNA molecule that is attached to the mesosome membrane, starts replicating at the initiating point which is located very near to the mesosome.


Nucleoids; www.schaechter.asmblog.org






 The chemical components of mesosomes are responsible for initiating replication, which will be completed in about 20-30 minutes.  Then the daughter molecules, still attached to the membrane, open out and segregate.  A little later, almost in the middle region of the cellular cytoplasm, the plasma membrane produces an inward invagination all-round and it progresses till the inwardly growing membranes fuse with one another in the center. Proteins such as FtsZ (similar to eukaryotic tubulins are involved. This results in the division of cytoplasm into two compartments.  Soon, the newly formed plasma lemma secretes the cell wall materials into the space found between them.  Then the middle wall splits across in the middle and two daughter cells separate.



Figure 1

Models for division-site selection in E. coli (Left) and B. subtilis (Right). MinD is in blue, MinE in yellow, FtsZ in green and DivIV in red. Shown are different stages of the cell cycle, beginning with a newborn cell and finishing with cell division that produces two daughter cells. (Left) In E. coli, MinE localizes to a ring-like structure at or near the middle of the cell early in the division cycle. MinD accumulates alternately at the membrane periphery on either side of the MinE ring (3). The alternation of MinD localization from one pole to the other occurs at a frequency of the order of tens of seconds. The rapid relocation of MinD ensures that no FtsZ ring is assembled at either the ¼ or ¾ sites in the cell halves. The presence of MinE at midcell prevents the MinD inhibitory activity at this site, allowing assembly of the FtsZ ring at this site. The MinE ring disassembles before completion of constriction. (Right) In B. subtilis, DivIVA and MinD are localized to the cell poles in a newborn cell, and therefore the presence of the MinD inhibitor prevents the formation of the FtsZ ring at these sites. Later, presumably after completion of DNA replication, a new potential division site is created at midcell. The sequestration of the MinD inhibitor to the poles allows assembly of the FtsZ ring at midcell and recruitment of other cell division proteins. At this point, the division machinery presumably becomes resistant to the MinD inhibition. DivIVA and MinD proteins then are recruited to the midcell. Constriction then is initiated. When constriction is completed, the FtsZ ring disassembles, but DivIVA and MinD remain at the newly formed poles, preventing further divisions from taking place in these polar sites. http://www.pnas.org/


It is important to note that this type of cell division does involve many complicated structures but the cell undergoes DNA duplication and cytoplasmic division by cleavage.




Multicellular organisms start their development as a unicellular zygote.  Under favourable conditions unicellular organisms multiply and produce a huge population. A fertilized egg may develop into a giant plant.  Some haploid organisms produce spores or gametes as a means of reproduction.  All the above processes are achieved by cell divisions.  This process involves equal distribution of genetic material. But in meiosis the genetic material is reduced to half of the original in the first division of meiosis.


















Animal cell Division




The process involves two important steps.  The first is the division of nucleus (karyokinesis) and the second which normally follows is called cytokinesis. Cytokinesis depending upon the cell type (organism) and stage produce two equal cells or cells show asymmetric or polarized cell division.


Animal and plant proteins that demonstrate various elements of asymmetric division

BASL, BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE; DUO1, duo pollen 1; FBL17, F-box like protein 17; MAPK, mitogen-activated protein kinase; MPK, Arabidopsis gene encoding a mitogen-activated protein kinase; PAN1, PANGLOSS 1; PAR, partitioning defective; PLL1, POLTERGEIST-LIKE 1; POL, POLTERGEIST; SSP, SHORT SUSPENSOR; WOX, WUSCHEL-related homeobox; YDA, YODA; Asymmetric cell division; http://f1000.com/




Further-more depending upon the presence or absence of astral elements, it has been classified into astral type and anastral type.  However, the whole process of cell cycle progresses sequentially through different stages, which merge with one another smoothly.  Basing on the complex biochemical and physical changes, different stages have been recognized.  The stages are interphase, prophase, metaphase, anaphase, telophase and finally cytokinesis.


The time required for these different stages vary from cell type to cell type and organisms to organisms.  Nevertheless, the interphase is the longest stage and the most variable.  For example: in the root meristems of Vicia faba and Pisum sativum, the total time required for the whole cell cycle is about 24 hours, out of which interphase occupies about 21 hours and a half.  On the other hand prophase to telophase requires just about two hours and a half.  On the contrary, in the corneal epithelial cells of rats, the whole process requires just 60 minutes whereas the interphase takes up 14-24 hours.


Interphase:  In yester years, interphase was considered as the resting stage, but in actuality it is one of the most active stages for it is the stage at which the cell prepares itself for the entire proceedings.  Because of its long duration and varied biochemical activities this stage has been further sub-divided into phases like G1, S and G2 of which G1 phase is the most variable in duration.  Intense biochemical activities take places in this stage and all precursors for DNA synthesis, histone synthesis, assembly of proteins etc., are either mobilized or synthesized.  Sometimes, the cell cycle gets arrested at this stage and undergoes a resting period called Go stage which ranges from few hours to years.  At this stage all activities of the cell come to stand still; such a stage is called G0 phase.  However, once the G1 stage is on, single stranded chromosomes move on to the next stage called ‘S’ phase.  At this stage chromosomes undergo duplication.  During this process, the long DNA double helix unwinds and semi-conservative replication is initiated at several points simultaneously.  Then the replication work progresses in both the directions till they meet the neighbouring replicons.  During replication, one of the daughter DNA molecules retains the parental histone core proteins and the other gets associated with the newly synthesized histone units to form a new chromatin thread.  Thus two chromatin strands are formed in about seven hours of time, while G1 stage takes about 5 hours.  Once the chromatin threads are duplicated, G2 phase is initiated.  At this stage intense biochemical activities required for chromosomal contraction and development of mitotic apparatus take place.  This state lasts for about 3 hours.  All these activities ultimately result in the increase of nuclear size and now the cell is set to enter into a dramatic condensation and movement phase.  It is important to note that through out this stage various types of RNAs are synthesized.  Even as the chromatin DNA is undergoing replication, RNA synthesis continues.



Cell cycle duration of each stage;

www2.le.ac.uk;www2.le.ac.uk; http://www.angelfire.com/


Action of different Cyclins and different CDKs at specific phases;

www.oregonstate.edu; and www.scielo.br

Regulator molecules of  the cell cycle; www.boundless.com; www.philschatz.com


                                 Role of E2F Family of proteins;www.nature.com


Orderly progression through these cell-cycle phases is controlled by the sequential activation of the Cyclin-dependent kinases (Cdks) Cdk4/6, Cdk2 and Cdc2. Their activity is regulated by various mechanisms, including the synthesis and binding of a specific regulatory subunit (called a Cyclin), both inhibitory and activating phosphorylation events, and the association/dissociation of inhibitory molecules called Cdk inhibitors (CDIs). Mitogenic growth factors exert their effect by promoting the synthesis of the D-type cyclins and their assembly into active Cdk4/6–cyclin D complexes. By contrast, the expression of cyclin E is triggered by internal signalling pathways and the appearance of Cdk2–cyclin E kinase activity seems to be synonymous with the restriction point. The ordered activation of the remaining Cdk–cyclin complexes seems to be self-regulating: each Cdk–cyclin complex triggers the activation of the next Cdk–cyclin species and also induces its own destruction. Under conditions of cellular stress, cell-cycle progression is disrupted by the activation of checkpoint pathways that ultimately lead to the inhibition of one or more Cdk–cyclin complexes. Jeffrey M. Trimarchi & Jacqueline A. Lees; Nature .com


Difference between Plant cytokinesis and Animal cytokinesis


Plant Mitosis

Animal mitosis

Centriole present

Centriole absent

Aster develops at each centriole

Aster does not form

Spindle formed-Astral type

Spindle-non astral type

Cytokinesis by furrowing or constriction

Cytokinesis by central plate formation

Mitosis occurs in all cells throughout body

Mitosis occurs mostly in meristems and during renewed cell division






Prophase sets in as cell cycle factors operating in regulating cell division events are ready to go.  The cell volume has reached a critical stage with all its components are build up, the nucleus meanwhile also enlarges as the  chromosomal DNA undergoes replication and the daughter chromatids fully form, the nuclear membrane starts dismemberment aided by lamin components as small membrane vesicles including pore complexes.  Appearance of mitotic apparatus and the dismemberment of Nuclear membrane coincide.


Metaphase: As the nuclear membrane disappears tractile fibers with continuous fibers appear in dome shaped form, which then called mitotic apparatus.  Tractile fibers join and attach with kinetochore microtubular elements.  By contractile mode the tractile fibers bring all the chromosomes (which divalent i.e contain two sister chromatids, but the centromere is still intact and single.  Interestingly, at CEN region kinetochore complex organizes on either side of the CEN region, thus all mitotic chromosomes contain two kinetochore complexes; they with their tractile fibers are oriented toward their respective poles.  It is at the end of the metaphase the CEN region appears to be split for the kinetochores bound by their respective tractile fibers are oriented towards their respective poles.


Anaphase: Once duplicated chromosomes with their chromatids placed in the mid region of the cell or what is called equatorial plate, start moving towards their respective opposite poles.






Animal cells; www.nature.com

General view not plant cells; www.cell.com

Mitotic spindle action at specific stages


In astral type cells, the beginning of the prophase is indicated by the division of centrioles and the formation of radiating fibres all-round these daughter centrioles.  As the nuclear volume increases, one of the astral points starts moving towards the other pole. Thus mitotic apparatus develops. Both in plant cells and animal cells tractile fibres which are associated with the kinetochore start depolymerizing at the poles.  Thus chromosomes move along with the tactile fibres.  Perhaps, simultaneously or at a little later stage, continuous fibres grow longer with the polymerization of tubulins from the polar ends.  Thus they stretch the mitotic spindle and greatly aid in the movement of chromosomes. This process requires ATP as the energy source.


Sliding Theory:  This theory envisages the presence of microfilaments associated with microtubules.  The presence of Actin and Myosin units at the polar regions has been detected by antibodies raised against actin and myosin.  Similar to that of muscular contraction, the microtubules of tactile fibres interact with acto-myosin proteins found at the poles and slide over each other.  Thus the contraction of tactile fibres towards the pole is brought about.  This process also requires ATP as the energy source.


Present concept:  Even though both the above said theories are attractive, each of them has its own drawbacks.  It is presumed that both the mechanisms may be operating simultaneously.  To begin with, the sliding mechanism starts pulling the tactile fibres at the poles, at the same time the tactile fibres undergo depolymerization and continuous fibres get elongated by polymerization of tubulins.  Nevertheless, the knowledge about the molecular mechanisms of the organization of mitotic apparatus and the exact role in chromosomal movement and cytokinesis is far from clear.


Telophase: In this stage single stranded chromatids that are pulled towards their respective poles start aggregating; simultaneously chromosomes start decondensation.   Thus the chromosomal strands become longer.  At this stage transcription activity of chromosomal DNA begins.  At the same time the nuclear membrane vesicles start appearing all-round the chromosomes and soon these membranous bits with pore complexes organize into nuclear envelope. The relaxed chromatin attaches to matrix proteins at regions called MARS.  As the chromosomal strands recoil and relax, the nucleolar DNA present in the region of secondary constriction loops out and nucleolar region begins to get organized. The nacked rRNA genes in clusters start transcribing precursor rRNAs.  It is at the same time very many pre-rRNA processing snoRNAs and their associated proteins assemble in the nucleolus.  A little later the incoming ribosomal structural proteins assemble on r.RNA and nucleolus gets organized.  It is important to note that chromosomes at this stage remain single stranded.




Chromosomal morphologies changes during different stages of Mitosis; http://plantphys.info/and www.rotarecuvi.exblog.jp



Generally karyokinesis leads to cytokinesis, but in certain organisms like plasmodia, siphonales algae and others, cytokinesis does not follow karyokinesis and repeated nuclear divisions lead to multinucleate cells or coenocytic cells.  Similarly, during early development of liquid endosperm in coconut fruits, nuclei divide repeatedly before cytokinesis sets in.  The mechanism of cytokinesis in animal cells and plant cells vary; in the former case it is achieved by cleavage and in the latter, cytokinesis takes place by phragmoplast formation.



Cytokinesis by cleavage:  In animal cells, cytokinesis sets in at late anaphase or early telophase.  The appearance of dense materials at the equatorial region of mitotic apparatus is the first indication of cytokinesis.  Gradually a number of membranous vesicles appear at this region and then a ring of depression further deepens into a constriction or deep furrow, finally it leads to the division of cytoplasm into two units.




However, during cleavage form of cytokinesis, at the equatorial region a ring of acto-myosin filaments appear in the cortical region of the cell.  Using ATP as the source of energy these acto-myosin filaments interact.  As a result the associated protein filaments contract and the membrane to which these protein filaments are bound is drawn inwards all-round till the membranes fuse in the middle.  Thus the cells get separated.  The exact mechanism of membrane contraction involving microtubules, actin and myosin and ATP is not clear.  Nevertheless the presence of these structures in and around the mitotic apparatus is known.  Their involvement in the cleavage is just a presumption, of course with valid reasons.



With the development of deep constriction, some of the spindle fibres disappear due to disassembly of microtubules into tubulin monomers.  Even after cleavage, some remnants of microtubules that are found at the centriole region, also disappears at the end.


Cytokinesis by Phragmoplast:  Plant cells which do not possess centrioles, during cytokinesis produce numerous membranous vesicles derived from Golgi complex and endoplasmic reticulum (SER).  These vesicles appear at the inter-zonal region of the equatorial plate as well as at the microtubules found at this region.  With time lapse, some more microtubules are added to the peripheral mitotic spindle. Thus the mitotic apparatus appears to be bulged.  Such a bulged structure of mitotic apparatus is called phragmoplast.  Later, the vesicles found in the equatorial region within the mitotic apparatus fuse with one another and for a circular membranous cisternae, which gradually extend laterally and

reach the phragmoplast surface.







File:Steps in plant cell cytokinesis.jpeg

Final steps in plant cytokinesis; http://php.med.unsw.edu.au/


          Plant cell Mitotic stages; www.searchpp.com


Cytokinesis plants;




Tomography cell plate

Electron tomographic view of cell plate formation: 

A cell plate in the tubular-vesicular network phase of cell plate formation; Secretory vesicles (small blue and green spheres) are trafficked down the phragmoplast microtubules (light green and magenta rods, mt) to fuse with the growing cell plate (yellow, cp). A few clathrin-coated vesicles (large red spheres) can also be seen budding from more mature sections of the plate and traveling along the phragmoplast MTs. The cell plate is enclosed within a ribosome-excluding cell plate-associated matrix (red dots, cpam). The large blue structures are mitochondria (m). For clarity, the endoplasmic reticulum is not shown. Image courtesy of Dr. José Seguí-Simmaro. http://www.illuminatedcell.com/;publishing.cdlib.org


Prior to division, the plant cell will have made numerous vesicles that contain the raw materials needed to create cell walls. These materials are held in an inert state, with inactive enzymes needed to form these materials into walls. As telophase begins, these vesicles begin to line up down the equator of the cell, and begin to fuse (what do you think triggers this action? will it trigger the enzymes?). As the vesicles fuse, cell walls begin to form. As more vesicles fuse (remember the membrane is dynamic), the wall continues to grow (cell plate). Eventually the membrane surrounded wall will fuse with the parental cell wall. Once the cell plate fuses with the parental wall, you have two new daughter cells. The cell plate also develop plasmodesmata for symplastic flow of liquids. Robert Maxwell 






Finally both the cisternae and phragmoplast reach the lateral plasma membrane and fuse with it.  Thus the cytoplasm gets divided into two compartments by the membranous cisternae which act as the newly formed plasma membranes of the daughter cells.  The space found between these membranes will be soon filled up by calcium pectate which acts as the middle lamella.  Then the Golgi complex derived vesicles filled with cellulose fibres are directed with the help of microtubules towards the newly formed middle lamellae and a few cells wall, made up of cellulose fibres, is laid on either side of the middle wall.  Thus two daughter cells are produced.


Significance of Mitosis 

All multicellular organisms, as well as unicellular organisms use mitosis as a mechanism for multiplication of cells.  During this process, chromosomes of parental cells duplicate and distribute equally to their daughter cells.  Here the term ‘equally’ denotes both quantitative as well as qualitative.  This process also helps in the growth of an organism.  In many organims where certain organs or cells are subjected to wear and fare, the cells are replaced continuously by mitosis, for example: in human beings there are about 2.5x1015; red blood cells and they have an average life of 420 days.  In order to maintain the constancy of the blood cells, the body produces about 2.5 million new cells every second to compensate the loss, which appears to be incredible, but human body does it with mitosis.

Control of the Cell Cycle;

Cell cycle is highly regulated, otherwise, if the cell division continues without any control cell lead to multiple numbers and leads to Cancer.





The passage of a cell through the cell cycle is controlled by proteins in the cytoplasm. Among the main players in animal cells are:

Their levels in the cell rise and fall with the stages of the cell cycle.

Their levels in the cell remain fairly stable, but each must bind the appropriate cyclin (whose levels fluctuate) in order to be activated.

They add phosphate groups to a variety of protein substrates that control processes in the cell cycle.





Mitosis and Cancer

Even though mitosis helps in the growth of an organism not only in the size but also in population, it is a highly related phenomenon.  By mutational studies in yeast cells, as many as 38 or more steps have been identified to take part in mitosis, of which some are highly crucial in the progression of mitotic stages.  If there are any mutations in the genome that control this process, cell division is completely inhibited or completely goes out of order or it may end up in an uncontrolled mitotic divisions.  Under normal conditions, particularly in multicellular organisms, mitotically derived cells undergo differentiation and perform specific functions. Instead, in an uncontrolled process, cells undergo continuous multiplication by repeated mitosis.  In these cases the cell derivatives do not undergo any differentiation, but they divide and redivide endlessly.  As a consequence of this, innumerable cells of the same kind are formed.  Such a group of cells which are endowed with a potentiality to divide and redivide ceaselessly is called tumor cells and the disease thus produced is referred to as cancer.  This can be induced by various carcinogenic agents like drugs, X-ray irradiations and even some viruses.  Certain spontaneous mutations may also cause growth.


The analysis of cancer cells indicates that the rapid and uncontrolled cellular divisions are due to some changes in the regulatory chromosomal proteins called non-histones.  Identification of such causative non-histones is very essential and important to cure the cancer disease.

In plants, however, callusing or callus formation is another example of uncontrolled, undifferentiated tumor formation.  Nevertheless the callus formation is known to be controlled by certain phytohormones like auxins.  The special feature of these hormones is that at particular concentration, they induce tumor formation in plant cells, but at a different concentration with other hormones like cytokinins, they may induce differentiation of shoots or roots.  The probable mechanism by which the hormones cause callus formation is again attributed to differential gene expressions or due to certain modifications of nonhistone proteins, which actually trigger off the cellular components to undergo such uncontrolled cell divisions.


Mitosis and cloning

Development of a multicellular organism always begins with the zygote which is nothing but the product of syngamy.  The zygote inturn undergoes repeated but controlled cell divisions which are followed by cell differentiation, where the cell derivatives develop into different types of cells which have their own characteristic structures and functions.  The overall growth of an organism thus depends upon a controlled, determinate cell division and differentiation.  The molecular basis of such cell differentiation is not clear, though certain differential gene expressions in E.coli, Drosophila and others have been very well studied.


Using the property of cell’s totipotency, where a single cell could be induced to develop into a complete organism, biologists have succeeded in the clonal propagation of plant in general and animals in specific cases.  Normally, the production of off springs involves sexual reproduction, where two parents contribute the gene pool through gametes.  Such offspring’s possess the mixture of genes from their parents.  Instead, if diploid cells of one of the parents are induced to develop into an offspring, then such offspring’s are referred to as clones.  Such clonal propagation is in vogue, particularly in plants, where the technique of tissue culture has been very well exploited.


In this process, a cell or a group of cells from any part of the plant body is explanted into a known solid or liquid agar based nutrient medium.  If the medium is appropriate and balanced with the required phytohormones, the cell or cells explanted develop into callus, from which numerous embryos can be induced at will.  Later, the embryos can be cultivated.  This method has been successfully employed in cultivating horticultural plants, crop plants and also plants which are difficult to multiply by vegetative propagation or by sexual reproduction.


It is important to note, that this process has employed mitosis as the most important mechanism for cell multiplication.  Nevertheless, this process of cell division is always followed or preceded by a regulated differentiation.  Inspite of recent technical innovations, the molecular mechanism of differentiation is not known.


Unlike plants, clonal propagation of animals has been successful only in certain cases like frogs and rats.  In these cases diploid cells from the somatic tissues, rather than germinal cells, have been successfully used.  Either by the transplantation of the somatic cell into the mother uterus, or by the transplantation of a nucleus taken out from the somatic cell into enucleated zygotic cell, complete animals have been grown in the laboratories.  Such animals have the genome of only one parent and such offspring’s are called clones.  Though clonal propagation of human beings has been attempted, the moral, social and ethical problems have deterred him from doing any further experiments.  Nevertheless, with the time and change of attitude towards the fellow human beings, perhaps, one day he may resort to such clonal propagation of man to preserve himself.


Even though clonal propagation of higher plants and animals has its own implications as well as limitations, cloning of genes by Genetic Engineering techniques has been the craze of the day; its application in the welfare of fellow human beings is unlimited.  Many genetic engineering industries have been set up in USA and other European countries.  The trials and tribulations in developing this elegant but sophisticated technique are unsurpassed in the recent history of molecular biology.  The pace of development in this field is phenomenal and it can be compared only to the space and computer technology.  Biologist have already succeeded in cloning of genes for insulin, growth hormone, interferon and work is in progress to clone nitrogen fixing genes (nif genes) into eukaryotic plants.  Hitherto, man has relayed on specific organisms as the source of gene products, unfortunately the labour, time and money spent to extract them was exorbitant.  Added to this, the recovery was extremely poor. But the cloning techniques have made life easy and these products can be synthesized on a large scale, thus the cost of production as come down which is a great boon for common man.




Plants like ferns and sweet pea reproduce by spores and gametes.  Higher animals produce gametes as a mode of reproduction. In all the above said cases and other innumerable organisms, the plant or the animal body is diploid (2 n), such organisms resort to sexual reproduction by means of gamates.


Meiotic cycle at specific stages; www.mysearch.org.uk




www.wikihow.com; www.pinterest.com



Stacks Image 94

Comparison of chromosome dynamics in meiosis and mitosis. From Forsburg, Mol Cell 9:703 (2002)(A) Mitosis in a cell with two chromosomes ensures that each daughter cell receives a copy of each chromosome. Importantly, while the apparatus of mitosis ensures that each daughter cell will have a copy of chromosome 1 and chromosome 2, it does not distinguish which one. That is, the daughters may end up with (1A and 2A), and (1B and 2B). Or, they may end up with (1A and 2B) and (1B and 2A). Since the sister chromatids are identical, this random orientation doesn't matter. The important thing is that the daughter cells have the exact same chromosome complement as the starting cell: one copy of chromosome 1 and one copy of chromosome 2. (B) In meiosis, the starting diploid is reduced to four haploids. The homologuous chromosomes are duplicated, and paired to one another. Following recombination (see text), the homologues separate in the MI division. The MII division separates the sister chromatids, similar to mitosis. Each daughter nucleus will receive a single chromatid from a single homologue; importantly, because of recombination, the four daughter nuclei will not be genetically identical. Meiosis Metaphase1 and Anaphase1; segregation-http://www-bcf.usc.edu/



The gametes like sperms and eggs fuse to produce a zygote which is the first cell generation of a new offspring.  For example: human body is made up of diploid cells.  The reproductive organs are also diploid.  If the cells of these germ lines produce gametes of diploid nature, the fertilized product will be tetraploid.  And in successive generations the ploidy level goes on increasing.  But this does not happen the offspring’s of the diploid parents will be always diploid.  This is achieved by a remarkable process called Meiosis.  The diploid reproductive cells produce haploid gametes by Meiosis, and such haploid gametes fuse to produce diploid off springs thus the diploid chromosomal number is maintained between parents and off springs by successive meiosis and fertilization.  Thus Meiosis is often considered as an antithesis for fertilizations.



Mechanism of Meiosis

Meiosis unlike mitosis takes place in spore bearing or gamete bearing cells. Most of the cells which are set to undergo meiotic division are quite large, distinct, rich in cytoplasm and possess large nucleus with a conspicuous nucleolus.  The cells show high rate of metabolic activity.  The duration of meiosis varies from organims to organism and from few hours to many days probably years.  It takes place in two successive stages (1) Meiosis I or Reduction state (2) Meiosis II or Equational division. Each of these stages further, shows sub stages like Interphase, Prophase, Metaphase, Anaphase, Telophase and Cytokinesis.



Interphase: This stage is a preparatory stage for the subsequent events of karyokinesis.  This, like mitosis, is also subdivided into G1, S & G2 stages.


G1 Stage:  It occupies quite a large period of time at which cell prepares for the duplication of chromosomes.  The necessary precursors like nucleotides, proteins and many rich molecules are mobilized.  As a consequence of this accumulation, the nuclear volume increases.  The chromosomes found at this stage are extremely thin and they are not clearly visible except for certain heteropycnotic chromatin regions which appear as darkly stainable segments.


S-Stage:  At this stage, hitherto single stranded chromosomes undergo duplication (through DNA replication, histone and nonhistone assembly) into double stranded chromosomes.  Still the chromosomes are not clearly visible.  However the nuclear volume further increases.


G2 Stage:  This stage is comparatively of shorter duration and cell enters into prophase.  The details of molecular events are not clearly known.


Prophase I:  This stage is relatively longer and most complex; basing on the behavior of chromosomes and appearance, this stage has been further divided into sub stages: sequentially these are referred to as leptotene, zygotene, pachytene, diplotene and diakinesis.  In all these stages, chromosomes continuously undergo condensation till metaphase.


Leptotene:  At this stage, the most invisible chromosomes gradually become visible.  This is due to condensation but still they appear to the single stranded structure, but are actually double stranded because of chromosomal duplication in the first interphase.  Here, most of the chromosomes appear to be looped into horse-shoe shaped structures, where the chromosomal ends are found to be associated with the nuclear membrane.  This association has been considered as very important for some proteins that are synthesized in the cytoplasm which get associated with chromosomes through the nuclear membranes.  This appearance of chromosomes has been referred to as “bouquet stage”, at this stage, chromosomes show fine granular or bead like structures called chromosomes. They were equated to genes (Bellings) but later they were found to be nothing but coiled expressions of chromosomes.


Appearance of synaptonemal elements and final synapsis; 




www.users.path.ox.ac.uk and http://www.carabinsnicois.fr/





Zygotene:  This is a stage which homologous chromosomes (derived from paternal and maternal side), start recognizing each other and initiate pairing.  The pairing may be initiated at any point, i.e. terminal, middle or any where.  However once the pairing is initiated it proceeds like a Zipper.  The process is so exact and precise; the pairing takes place– chromomere by chromomere and gene to gene.  In any one of the homologous pair of chromosomes, if there is any non-homologous segments get paired.  If there are any segments of chromosomes which remain non-replicated, they replicate at this stage and the DNA that is replicated is called Z-DNA which is rich in GC content.


Synaptonemal elements found between meiotic prophase chromatin; www.mun.ca


Structural features of synaptic elements

Synaptosomal elements; http://www.lookfordiagnosis.com/





Synapsis:  The pairing of homologous chromosomes, though dramatic and fascinating to observe, the forces and factors that are responsible for recognizing each homologous factors that are responsible for recognizing each homologous pair, and mechanists movement of chromosomes, have still remained unexplained.  Nevertheless, electron microscopic studies of some animal cells have revealed the presence of a ribbon shaped protein complex associated with the paired homologous chromosomes.  This complex has been named as Synaptonemal Complex.



Three specific components of the synaptonemal complex have been characterized: SC protein-1 (SYCP1), SC protein-2 (SYCP2), and SC protein-3 (SYCP3). In humans, the SYCP1 gene is on chromosome 1p13; the SYCP2 gene is on chromosome 20q13.33; and the gene for SYCP3 is on chromosome 12q.www1.qoloq.com


Three specific components of the synaptonemal complex have been characterized: SC protein-1 (SYCP1), SC protein-2 (SYCP2), and SC protein-3 (SYCP3). In humans, the SYCP1 gene is on chromosome 1p13; the SYCP2 gene is on chromosome 20q13.33; and the gene for SYCP3 is on chromosome 12q. Three specific components of the synaptonemal complex have been characterized: SC protein-1 (SYCP1), SC protein-2 (SYCP2), and SC protein-3 (SYCP3). In humans, the SYCP1 gene is on chromosome 1p13; the SYCP2 gene is on chromosome 20q13.33; and the gene for SYCP3 is on chromosome 12q.

The synaptonemal complex (SC) was described by Montrose J. Moses in 1956 in primary spermatocytes of crayfish and by D. Fawcett in spermatocytes of pigeon, cat and man. As seen with the electron microscope, the synaptonemal complex is formed by two "lateral elements", mainly formed by SYCP3 and secondarily by SYCP2, a "central element" that contains at least two additional proteins and the amino terminal region of SYCP1, and a "central region" spanned between the two lateral elements, that contains the "transverse filaments" composed mainly by the protein SYCP1.

The SCs can be seen with the light microscope using silver staining or with immunofluorescence techniques that label the proteins SYCP3 or SYCP2.

This "tripartite structure" is seen during the Pachytene stage of the first meiotic prophase, both in males and in females during gametogenesis. Previous to the pachytene stage, during leptonema, the lateral elements begin to form and they initiate and complete their pairing during the zygotene stage. After pachynema ends, the SC usually becomes disassembled and can no longer be identified.

Formation of the SC usually reflects the pairing or "synapsis" of homologous chromosomes and may be used to probe the presence of pairing abnormalities in individuals carrying chromosomal abnormalities, either in number or in the chromosomal structure. The sex chromosomes in male mammals show only "partial synapsis" as they usually form only a short SC in the XY pair. The SC shows very little structural variability among eukaryotic organisms despite some significant protein differences. In many organisms the SC carries one or several "recombination nodules" associated to its central space. These nodules are thought to correspond to mature genetic recombination events or "crossovers".

In cell development the synaptonemal complex disappears during the late prophase of meiosis I.

One aspect of meiosis research (in genetics, molecular biology, and reproductive medicine) involving synaptonemal complexes is how they (or what they do) can be affected and damaged by chemical exposure, specifically by toxins likebisphenol A (an experiment at Harvard Medical School by Dr. Monica Colaiácovo, Ph.D., an associate professor of genetics, involved dosing C. elegans worms with that toxin and then verifying the results in mouse studies) www.wekipedia.org


Synaptonemal components




Synaptonemal Complex:  This complex appears at the late leptonema or early zygonema establishes fully at zygonema and pachynema.  This structure starts disappearing at the diplonema. Synaptonemal complex is exclusively made up of protein units, arranged in between a pair of homologous chromosomes in the form of a paired ribbon.  It consists of a pair of axial, a pair of lateral and a single central filament is the overlapping structure extended from the axial filaments.  The space found between a pair of axial filaments, lateral filaments is 0.15µm to 2 µm. On the other side of the axial filaments, lateral filaments are present and these are associated with the homologous chromatin material.  Some of the chromatin material penetrates through these protein complexes and open out into the central region as free DNA segments.  These may consists of individual genes or a group of gene segments.  The genetic material that is extruded from both the homologous chromosomes align parallel to each other, such that recombination may be brought about.  Notwithstanding the above observation, the nature of the proteins and their functional mechanisms in pairing and recombination has remained as an enigma. It has been speculated that the synaptonemal complex is made up of proteins, which not only recognize the homologous segments of chromosomes, but also bring about the pairing and recombination of genetic material between them.


Pachytene:  At this stage, if there are any parts of homologous chromosome unpaired, the paring will be completed.  Then, at certain points, the chromosomal materials between homologous pairs exchange.  This phenomenon is referred to as recombination or crossing over.  This involves breakage and reunion between crossing over.  This involves hologous chromosomes.  Use of radio-active precursors have shown that the chromosomal material, get degraded and resynthesized.  The enzymes that are involved in this process have been recognized as specific endonucleases, DNA polymerases, ligases and exonucleases.




Mechanism of cross over:  Basing on the microscopic observation of meiotic chromosomes, Darlington has opined that homologous chromosomes pair and coil relationally at zygotene under great strain.  This coiling brings about great torsion and strain on chromonemal strands.  Because of this, sister chromatids of both homologous chromatids break at these points.  This breakage releases the torsion and strain; the chromatids recoil and come to rest.  If the broken ends of the non sister chromatids of two homologous chromosomes are brought near to each other, then they join, thus crossing over is brought about, resulting in genetic exchange between the parental chromosomes.  Thus crossing over is often summed up as the phenomenon of breakage and reunion between two non-sister strands of two homologous chromosomes.  At the gross level this appears to be true.  But break down and the reunion of chromosomes involve the breakdown of chromatin materials like proteins, DNA, and the rejoining involves the resynthesis and reassembly of the chromosomal proteins. 

Diagram of crossing-over. Note that while crossing over is shown here, for simplicity, between only one of the two chromatids of each chromosome, each chromatid of each chromosome actually synapses with one of the chromatids of that chromosome's homolog. So crossing-over between both of the synapsed chromatid pairs does occur.www.macroevolution.net




Chromosomal DNA pairing and recombination; katyperrybuzz.blogspot.com



Molecular Mechanism of crossing over:  When homologous chromosomes are brought together or paired by synaptonemal complex, some of the segments or chromosomal regions of homologous chromosomes get disassociated with chromosomal proteins and the DNA strands from the apposing chromosomes loop out with the central region found between two axial filaments of SC.


During meiosis, a programmed induction of DNA double-strand breaks (DSBs) leads to the exchange of genetic material between homologous chromosomes. These exchanges increase genome diversity and are essential for proper chromosome segregation at the first meiotic division. Recent findings have highlighted an unexpected molecular control of the distribution of meiotic DSBs in mammals by a rapidly evolving gene, PR domain-containing 9 (PRDM9), and genome-wide analyses have facilitated the characterization of meiotic DSB sites at unprecedented resolution. In addition, the identification of new players in DSB repair processes has allowed the delineation of recombination pathways that have two major outcomes, crossovers and non-crossovers, which have distinct mechanistic roles and consequences for genome evolution. Frédéric Baudat et al ; http://www.nature.com/


Meiotic recombination in mammals: localization and regulation; Frédéric Baudat, Yukiko Imai and & Bernard de Massy

During meiosis, a programmed induction of DNA double-strand breaks (DSBs) leads to the exchange of genetic material between homologous chromosomes. These exchanges increase genome diversity and are essential for proper chromosome segregation at the first meiotic division. Recent findings have highlighted an unexpected molecular control of the distribution of meiotic DSBs in mammals by a rapidly evolving gene, PR domain-containing 9 (PRDM9), and genome-wide analyses have facilitated the characterization of meiotic DSB sites at unprecedented resolution. In addition, the identification of new players in DSB repair processes has allowed the delineation of recombination pathways that have two major outcomes, crossovers and non-crossovers, which have distinct mechanistic roles and consequences for genome evolution.

Recombination can be homologous between sequences that are nearly equal at meiosis, or site specific- between sequences with a limited stretch of similar sequences or transposition- where DNA elements move from one site to another, where similar sequences are involved


Model for the role of PRDM9 in meiotic DSB localization.

PR domain-binding 9 (PRDM9) binds to a specific DNA motif (brown squares) through its C2H2 zinc finger array (blue oblong). Subsequently, the PR/SET domain (PRDI-BF1 and RIZ homologous region, a subclass of SET domains; http://www.nature.com/

 Base excision repair (BER) and nucleotide excision repair (NER) pathways. Both BER and NER repair pathways utilize the complementary DNA strand to restore sequence information lost in the damaged DNA strand. A) Schematic representation of the basic steps followed during short-patch BER (see text for details). B) Main sequence of events and enzymatic activities implicated in NER. C) Forms of lesions generated in the DNA by IR. Emil Mladenov and George Iliakishttp://www.intechopen.com/

Molecular events during recombination


Crossover junction and branch migration; http://users.path.ox.ac.uk/




At various points, all along the length of chromosome start aligning with each other so that the homologous DNA segments are brought near as well as parallel to each other.  Then certain endonucleases found in synaptonemal complex cut open the DNA strands as shown in the figure.





As a result, the DNA segments break open with long sticky ends of DNA belonging to homologous pair of chromosomes have complementary nucleotide sequences.  This leads to the cross pairing of the single stranded DNA ends.  This pairing may result either in the overlapping with some part of the segment sticking out or certain gaps may be left out.  In the former condition exonucleases cut out the extra DNA segment and in the latter case, gaps are filled up by DNA polymerases.  DNA synthesized at the time of genetic recombination is called P.DNA.  However, the strands are finally sealed by DNA ligases.  Thus crossing over or recombination is brought about.  Such recombination events, particularly in prokaryotic organims like bacteria have been observed through electron microscope.  But in Eukaryotic organisms the visibility, even under high voltage electron microscope is not clear.  However, indirect studies like the incorporation of radioactive DNA precursors into meiotic chromosomes, have added some evidence to this theory.  Further more, the presence of dense nodules of 100 nm size found in the central component of SC have been assumed to be recombination nodules, involved in genetic exchange.


Diplonema:  The duration of this stage varies from few hours to many years.  for example in human females, oocytes develop in the germ line; when the human embryo is 5 months old, the oocytes start meiosis and reach up to diplonema and stop.





At this stage meiosis gets arrested till the females reach the puberty, then the oocytes one by one complete meiosis and eggs are released periodically till the age of 50 years more or less.


In this stage of diplonema the pairs of homologous chromosomes start moving away from each other, probably because of the disappearance of synaptonemal complex.  As the chromosomes repel at each other parts of chromosomal segments are still held at the regions of chromosomal exchange, which show up as X configurations and they are called chiasmata.  As the chromosomes further open out, the chiasma starts slipping away along the chromosomal strands.  This phenomenon is called Terminalization.


Diakinesis: At this stage chromosomes complete the terminalization and whatever synaptonemal complex that has remained, disappears completely.  Meanwhile the chromosomes reach maximum condensation.


The disappearance of nuclear membrane and nucleolus marks the end of Diakinesis and Prophase.


Metaphase I:  With the disappearance of nuclear membrane, mitotic apparatus appears.  The tactile fibres get attached to the kinetochore regions of the centromere of the double stranded chromosomes.  Unlike mitotic metaphase chromosomes in this stage each of the homologous chromosomes will have only one kinetochore, though centromere appears to be double.  The tactile fiber drag the respective homologous chromosomes will have only one kinetochore, though centromere appears to be double.  The tactile fiber drag the respective homologous chromosomes on the metaphasic plate or equatorial plate and orient the homologous chromosomes in such a way, one of the homologous chromosomes is directed towards one pole and the other is to the opposite pole. Thus a pair of homologous chromosomes found on the equatorial plate will have one group of tactile fibres emanating from one kinetochore of one set of chromosomes and another group of tactile fibres from the other chromosomes, which are directed to opposite poles.  This particular orientation is remarkable, for it is this that ensures reduction division.  Furthermore, the centromeres of the metaphasic chromosome do not divide and double strands of each homologous chromosome remain intact.


Another interesting, as well as important aspect is that during the orientation of homologous pair in the equatorial region, the maternal and paternal chromosomes are at random.  This results in the random and independent assortment of genes.


Anaphase:  The respective homologous chromosomes are pulled to their respective poles.  During this movement chromosomes undergo decondensation slightly.  The mechanism of chromosomal movement is same as that of mitotic Anaphase movement.


Telophase:  All the chromosomes that move towards their respective poles are pulled together and chromosomes undergo further decondensation resulting in the formation of chromatin network.




Interphase II and Prophase II:  The interphase is the shortest stage.  Some times the meiotic cells skip the interphase and they directly move on the metaphasic stage.


Metaphase II:  The mitotic apparatus appears at this stage with a different polarity.  Chromosomes are brought to the equatorial region and the chromosomes are oriented in such a way that the tactile fibers originate from kinetochrores that develop on either side of the centromere.  The tactile fibres are oriented in the opposite direction.  The centromeric region divides horizontally into two, which makes the end of metaphase.

Chromosomal exchange and separation; www.slideshare.net






Anaphase II & Telophase II: These single stranded chromosomes are now pulled to their respective poles.  During these stages, chromosomes undergo further decondensation.  Finally all the chromosomes in their respective poles get organized into a net work of chromatin.  Later nuclear membranes and their nucleoli appear.


Thus, starting from the single diploid nucleus, four nuclei with haploid chromosomal sets are formed.


Cytokinesis:  In the case of animal cells the cytokinesis is by cleavage formation, on the contrary phragmoplasts are formed in plant cells.  However, the cytokinesis always takes place after complete karyokinesis.  This may be successive or simultaneous.  The cour cells they derived from meiotic division are called tetrads.  These may further develop either into haploid spores or haploid gametes, which again depends upon the organims and the stage of life cycle.



Chromosomal segregation and events at which genes segregate or assort



Factors segregate and assort




Neurospora spore formation and genes assortment



Importance of Meiosis;

  1. It acts as an antithesis for fertilization.  Genetic recombination takes place between parental homologous chromosomes.


  1. As parental homologous chromosomes arrange randomly at first metaphasic plate, chromosomes segregate randomly but independently.


  1. Genetic recombination and random segregation result in the production of gametes with variable genotype.


  1. Variable genotypes help in bringing about variation result in the production of gametes with variable genotype.


  1. This variation plays a significant role in evolution.







1.    It is an equational cell division

It is a reductional cell division.



2.    Chromosome number is maintained between cell generation.

Chromosome number is reduced to half the original number



3.    If helps in the growth of the population of cells and it takes place during growth and development

It takes place during gameto genesis.



4.    This process takes place at 5 different stages viz. Interphase, prophase, Metaphase, Anaphase and Telophase.

This process takes place at two stages called Meiosis I and Meiosis II.  Prophase I is further sub-divided into Leptotene, Zygotene, Pachytene, Diplotene and Diakinesis.


5.    Homologous chromosomes do not pair, do not exchange chromosomal segments by crossing over.

Homologous chromosomes pair and undergo crossing over.



6.    Homologous chromosomes do not undergo segregation.

They undergo random but independent segregation.



7.    The daughter cells produced are qualitatively and quantitatively similar and do not exhibit any variation

The daughter cells produced are qualitatively ad quantitatively dissimilar and exhibit variation.




Meiosis and the Cell Cycle;

The special behavior of the chromosomes in meiosis I requires some special controls. Nonetheless, passage through the cell cycle in meiosis I (as well as meiosis II, which is essentially a mitotic division) uses many of the same players, e.g., MPF and APC. (In fact, MPF is also called maturation-promoting factor for its role in meiosis I and II of developing oocytes.


Checkpoints: Quality Control of the Cell Cycle;

The cell has several systems for interrupting the cell cycle if something goes wrong.

Spindle checkpoints. Some of these that have been discovered

All the checkpoints examined require the services of a complex of proteins. Mutations in the genes encoding some of these have been associated with cancer; that is, they are oncogenes. This should not be surprising since checkpoint failures allow the cell to continue dividing despite damage to its integrity.



ATM (="ataxia telangiectasia mutated") gets its name from a human disease of that name, whose patients — among other things — are at a greatly increased (~100 fold) risk of cancer. The ATM protein is involved in


MAD (="mitotic arrest deficient") genes (there are two) encode proteins that bind to each kinetochore until a spindle fiber (one microtubule will do) attaches to it. If there is any failure to attach, MAD remains and blocks entry into anaphase (by inhibiting the anaphase-promoting complex).

Mutations in MAD produce a defective protein and failure of the checkpoint. The cell finishes mitosis but produces daughter cells with too many or too few chromosomes, a condition called aneuploidy. More than 90% of human cancer cells are aneuploid.

Infection with the human T-cell lymphotropic virus-1 (HTLV-1) leads to a cancer (ATL = "adult T-cell leukemia/lymphoma") in about 5% of its victims. HTLV-1 encodes a protein, called Tax, that binds to MAD protein causing failure of the spindle checkpoint. The leukemic cells in these patients show many chromosome abnormalities including aneuploidy.

A kinesin that moves the kinetochore to the end of the spindle fiber also seems to be involved in the spindle checkpoint.


Many times a cell will leave the cell cycle, temporarily or permanently. It exits the cycle at G1 and enters a stage designated G0 (G zero). A G0 cell is often called "quiescent", but that is probably more a reflection of the interests of the scientists studying the cell cycle than the cell itself. Many G0 cells are anything but quiescent. They are busy carrying out their functions in the organism. e.g. secretion and attacking pathogens.

Often G0 cells are terminally differentiated: they will never reenter the cell cycle but instead will carry out their function in the organism until they die.

For other cells, G0 can be followed by reentry into the cell cycle. Most of the lymphocytes in human blood are in G0. However, with proper stimulation, such as encountering the appropriate antigen, they can be stimulated to reenter the cell cycle (at G1) and proceed on to new rounds of alternating S phases and mitosis.

G0 represents not simply the absence of signals for mitosis but an active repression of the genes needed for mitosis. Cancer cells cannot enter G0 and are destined to repeat the cell cycle indefinitely. http://users.rcn.com/jkimball.ma.ultranet.