The Biological Basis of Life

Human Chromosome

Chromosome is derived from two words, 'chroma' which means colour and soms' which means body. So chromosome simply means coloured thread like or filamentous body which are present in the nucleoplasm of living cells that mea in the nucleus of living cells. Basically they are carriers of genes and genes are units of heredity that means they help in inheritance or transmission of characters from one generation to the next. Chromosomes were first observed in plant cells by Karl Wilhelm Von Nageli in 1842 and their behaviour was described first by Walther Flemming in 1882.The particular term ' anatomist Von Waldeyer in 1888.

Chromosome :

Chromosome is made up of proteins and nucleic acid (DNA - Deoxyribonucleic acid). And structurally chromosome is made up of two chromatids, that means two arms, double stranded DNA and protein, and these two double strands are bound together at the primary constriction which is called a Centromere.

Therefore a Centromere usually divides the chromosome into two arms. One of the arms is comparatively short, another arm maybe comparatively long or maybe equal. But if one arm is short and the other arm is long the shorter arm is called P arm and the longer arm is called Q arm.

And in a chromosome the P arms are always arranged in a top orientation or position, whereas the Q arms face downwards.

An on the basis of the position of Centromere we can classified chromosome into four types - One is Metacentric so Metacentric are those chromosome in which the centromere is median or nearly in the medal of the arms.

And such chromosome therefore has two well defined arms with a length ratio varying from 1 : 1 to 2.5 : 1 than we have the Second category or Second type of chromosome that is Sub-metacentric Chromosome. They have unequal arms and are almost L shape. The ratio of the arms lies in between the ratio of Metacentric Chromosome and Acrocentric Chromosome.

Acrocentric Chromosome. Here, in Acrocentric Here, Chromosome, Centromere is closed to in Acrocentric one end of the Chromosome. As such one arm is substantially smaller than the other. And the ratio ranges from 3 : 1 to 10 : 1 than, finally we have Forth type of chromosome that is Telocentric Chromosome, here in Telocentric Chromosome, Centromere is strictly terminal that means Chromosome has only one arm. The terminal part being Centromere. So, these are different types of chromosome base on the position of Centromer.

Karyotype

A 'Karyotype' is derived from a Greek word 'Karyon' which means kernel, seed or nucleus. So a Karyotype is the number and appearance of chromosome in the nucleus of a eukaryotic cell. The term Karyotype is also used for the complete set of chromosomes or chromosome complement in a species or individual organism.

A Karyotype therefore refers to the complement of chromosomes either at specie level or individual level. It describes the number of chromosomes, structure under the light microscope and while doing so due importance should be given to their length, that means the length of the arms, the position of the Centromere, the bending pattern, any other difference between sex chromosome and also any other physical characteristics.

Therefore, when we talk of chromosome complement we look into various characteristics of a chromosome for identifying and systematically grouping chromosomes.

The technique of determining the Karyotype is usually called Karyotyping and the study of whole sets of chromosomes is sometimes known as Karyology. When chromosomes are arranged in a standard format that means in pairs because chromosomes usually occurs in pairs and according to the size and position of the Centromere it is known as 'Karyogram' or 'Idiogram'.

Human Karyotyping

It was in 1912 that Hans Von Winiwarter reported that there are 47 chromosomes in Spermatogonia and 48 in Oogonia thereby concluding that females have XX chromosomes and males have XO chromosomes.

This was the sex determining mechanism. Explained by Winiwarter. Later on it was Painter in 1992 though he was not certain whether the diploid of human was 46 or 48, he first favoured the 46 number but later on revised his opinion to 48.

He however correctly insisted on humans having an XX or XY system. So number of human chromosomes remained at 48 for over nearly 30 years. Finally it was Joe Hin Tjio on the basis of his publication in 1956 that the normal human Chromosome complement or Karyotype.

It is a well-known and established fact that human beings have 46 chromosomes or 23 pairs. Coming to the human Somatic (body) cells, it has two complete sets of chromosomes, one set given by each parent. These two sets together constitute the diploid condition represented by 2n that means one n given by mother and the other n by the father constituting 2n in diploid condition. Therefore 2n chromosomes in human are 46 in number.

Coming to the sex cell, the gametes, egg and sperm, they have only one set (23 chromosomes), this is known as the 'haploid' condition. This means we have two types of chromosomes autosomes' having 22 pairsor 44 chromosomes and 'gonosomes' or sex chromosomes with one pair or two chromosomes.

The sex chromosome in a male is XY, i.e., hemizygous and in a female is XX, i.e., homozygous. The human normal Karyotype when observed under the microscope particularly at the mitotic metaphase stage 46 chromosomes can be seen, 46 coloured blocks 2 of which are either XX or XY.

Chromosome Groups:

Now let us go a little bit deeper on human chromosome complement. These 46 chromosomes can be divided into 7(seven) different groups on the basis of the structure of the chromosome and the length of the arm from the Centromere. In the first group, A, we have chromosomes 1, 2 and 3.

These are large Metacentric chromosomes. In the second group B, comes chromosomes 4 and 5. These are large Sub-metacentric ones and are all similar. In the third group, C, we have chromosomes 6, 7, 8, 9, 10, 11 and 12 along with the X chromosome.

Structurally these are sub-metacentric and are of medium size. In the fourth group D, we have chromosomes 13, 14 and 15. These are again medium sized but acrocentric, i.e., having a very short arm and a very comparatively long arm plus a satellite so they are medium sized. In the fifth group E, chromosome 16, 17 and 18 comes under this group.

They are short in length, they are metacentric, however, the chromosome 17 and 18 are Sub-metacentric, that means out of the three the 16th is short and Metacentric and chromosomes 17 and 18 are Sub-metacentric. Coming to the sixth group F, we have chromosomes 19 and 20, these are again short and Metacentric.

In the last group G, we have chromosomes 21, 22 and Y. These are basically short Acrocentric with a satellite; however in case of Y there is no satellite. So, these are different types or groups of chromosomes of the human body. So, when we talk of chromosome complement we mean these seven different groups, these seven we mean these seven different groups, these seven.

Abnormal Chromosome Complements

Apart from these we have other abnormal human chromosome complements. One such condition is Down's syndrome which we often call Mongoloid syndrome. Here there is one extra copy of 21st chromosome that is why we call it as Trisomy chromosome. Though in a normal human karyotype we have 46 chromosomes, in Down's syndrome there are 47 chromosomes and this extra chromosome is a copy of the 21st chromosome.

Then we have another example - Edward's syndrome. An individual with Edward's syndrome will have 47 chromosomes, 46 plus one extra copy of 18th chromosome. Usually individuals with such an 18th extra chromosome have retardation of motor functioning, a number of congenital diseases or abnormalities causing serious health problems and usually 90 pc of those effected by Edward's syndrome die in infancy.

Another category is Klinifelter's syndrome. Here the chromosome complement is XXY, we already know that for male it is XY and for females it is XX, we can say that the Y chromosome determines whether one is male or female. Thus in this syndrome we have both the characters of the male as well as the female.

Basically people with Klinifelter's syndrome are males who are generally sterile, taller and heavier, longer arms and legs and they are often shy and quite with higher incidence of speech delay and dyslexia. Without testosterone treatment some may develop gynocosmastia during puberty.

We have another syndrome called Patau's syndrome. This is also called the syndrome of Trisomy 13 that means an extra copy of the 13th chromosome.

Then we have the XXX syndrome having XXX chromosomes, so here when XX denotes a female, there is another extra X chromosome. Such girls tend to be tall and thin and have higher incidence of dyslexia.

Then there is a very popular syndrome known as Turner's syndrome. In Turner's syndrome there is only one X instead of XX or XY chromosomes, that means either X or Y is missing. Naturally the chromosome complement of such an individual will be X0. Individuals with this syndrome often have a short stature, low hairline, abnormal eye features and bone development and a "caved in" appearance to the chest.

Similarly we have XYY syndrome. XYY definitely should mean a boy because of the XY combination. There is however an extra Y chromosome. Thus chromosome complement will be 47, 46 plus an extra Y chromosome. Such individuals will be taller than their siblings. Similar to individuals with XXX and XXY they are more likely to have learning difficulties.

Cell Division: Mitotic and Meiosis

Most human cells are frequently reproduced and replaced during the life of an individual. However, the process varies with the kind of cell. Somatic, or body cells, such as those that make up skin, hair, and muscle, are duplicated by mitosis.

The sex cells, sperm and ova, are produced by meiosis in special tissues of male testes and female ovaries. There are two kinds of cell division: mitosis and meiosis. Since the vast majority of our cells are somatic, mitosis is the most common form of cell replication. Mitosis is essentially a duplication process: It produces two genetically identical "daughter" cells from a single "parent" cell.

One grows from a single embryonic cell to a fully fledged person through mitosis. Even after one has grown, mitosis replaces cells lost through everyday wear and tear. The constant replenishment of your skin cells, for example, occurs through mitosis.

Mitosis takes place in cells in all parts of our body, keeping your tissues and organs in good working order. Meiosis, on the other hand, is quite different. It shuffles the genetic deck, generating daughter cells that are distinct from one another and from the original parent cell.

Although virtually all of our cells can undergo mitosis, only a few special cells are capable of meiosis: those that will become eggs in females and sperm in males. So, basically, mitosis is for growth and maintenance, while meiosis is for sexual reproduction.

Cell division involves the distribution of identical genetic material, DNA, to two daughters cells. What is most remarkable is the fidelity with which the DNA is passed along, without dilution or error, from one generation to the next.

Cell Cycle

All cells are produced by divisions of pre-existing cell. Continuity of life depends on cell division. A cell born after a division, proceeds to grow by macromolecular synthesis, reaches a species determined division size and divides. This cycle acts as a unit of biological time and defines life history of a cell. Cell cycle can be defined as entire sequence of events happening from the end of one nuclear division to the beginning of the next. The cell cycle involves the following three cycles.

1. Chromosome cycle

In it DNA synthesis alternates with mitosis (or karyokinesis or nuclear division). During DNA. synthesis, each double-helical DNA molecule is replicated into two identical daughter DNA molecules and during mitosis the duplicated copies of the genome are ultimately separated.

2. Cytoplasmic cycle

In it cell growth alternates with cytokinesis (or cytoplasmic division). During cell growth many other components of the cell (RNA, proteins and membranes) become double in quantity and during cytokinesis cell as a whole divides into two. Usually the karyokinesis is followed by the cytokinesis but sometimes the cytokinesis does not follow the karyokinesis and results into the multinucleate cell, e.g., cleavage of egg in Drosophila.

3. Centrosome Cycle

Both of the above cycles require that the centrosome can be inherited reliably and duplicated recisely in order to form two poles of the mitotic spindle; thus, centrosome cycle forms the third component of cell cycle.

Howard and Pelc (1953) have divided cell cycle into four phases or stages G1, S, G2, and M phase. The G1 phase, S phase and G2 phase are combined to from the classical interphase.

G 1 Phase:

After the M phase of previous cell cycle, the daughter cells begin G1 of interphase of new cell cycle. G1 is a resting phase. It is called first gap phase, since noDNA synthesis-takes place during this stage; currently, G1 is also called first growth phase, since it involves synthesis of RNA, proteins and membranes which lead to the growth of nucleus and cytoplasm of each daughter cell towards their mature size (Maclean and Hall, 1987). During G1 phase, chromatin is fully extended and not distinguishable as discrete chromosomes with the light microscope.

G1 phase is most variable as to duration; it either occupies 30 to 50% of the total time of the cell cycle or lacks entirely in rapidly dividing cells (e.g., blastomeres of early embryo of frog and mammals). Terminally differentiated somatic cell (i.e., end cells such as neurons and striated muscle cells) at no longer divide, are arrested usually in the G1 stage; such a type of G1 phase is called G0 phase.

S Phase

During the S phase or synthetic phase of interphase, replication of DNA and synthesis of histone proteins occur. New histones are required in massive amounts immediately at the beginning of the S period of DNA synthesis to provide the new DNA with nucleosomes. Thus, at the end of S phase, each chromosome has two DNA molecules and a duplicate set of genes. S phase occupies roughly 35 to 45% of cell cycle.

G Phase

This is a second gap or growth phase or resting phase of interphase. During G2 phase, synthesis of RNA and proteins continues which is required for cell growth. It may occupy 10 to 20% time of cell cycle. As the G2 phase draws to a close, the cell enters the M phase.

M Phase

A nuclear division (mitosis) followed by a cytoplasmic division (cytokinesis). The period between mitotic divisions that is, G1, S and G2 is known as interphase.

Mitosis

Mitosis is a form of eukaryotic cell division that produces two daughter cells with the same genetic component as the parent cell. The term mitosis was introduced by Walther Fleming (1882).

Chromosomes replicated during the Synthetic phase are divided in such a way as to ensure that each daughter cell receives a copy of every chromosome. In actively dividing animal cells, the whole process takes about one hour.

The replicated chromosomes are attached to a 'mitotic apparatus' that aligns them and then separates the sister chromatids to produce an even partitioning of the genetic material. This separation of the genetic material in a mitotic nuclear division (known as karyokinesis) is followed by a separation of the cell cytoplasm in a cellular division (known as cytokinesis) to produce two daughter cells.

In some single-celled organisms mitosis forms the basis of asexual reproduction. In diploid multicellular organisms sexual reproduction involves the fusion of two haploid gametes to produce a diploid zygote. Mitotic divisions of the zygote and daughter cells are then responsible for the subsequent growth and development of the organism. In the adult organism, mitosis plays a role in cell replacement, wound healing and tumour formation.

Mitosis, although a continuous process, is conventionally divided into five stages: prophase, prometaphase, metaphase, anaphase and telophase. (Greek: pro means before; meta means middle; ana means back; telo means end).

Prophase:

The chromatin, which is diffused in interphase are slowly condenses into well-defined chromosomes. The nuclear membrane breaks down to form a number of small vesicles and the nucleolus disintegrates. A structure known as the centrosome duplicates itself to form two daughter centrosomes that migrate to opposite ends of the cell.

The centrosomes organise the production of microtubules that form the spindle fibres that constitute the mitotic spindle; this is a bipolar structure composed of microtubules and associated proteins. In this phase, the chromosomes condense into compact structures. Each replicated chromosome can now be seen to consist of two identical chromatids (or sister chromatids) held together by a structure known as the centromere. Prophase occupies over half of mitosis.

Prometaphase

The chromosomes, led by their centromeres, migrate to the equatorial plane in the mid- line of the cell at right-angles to the axis formed by the centrosomes. This region of the mitotic spindle is known as the metaphase plate.

The spindle fibres bind to a structure associated with the centromere of each chromosome called a kinetochore. Individual spindle fibres bind to a kinetochore structure on each side of the centromere. The chromosomes continue to condense.

Metaphase

In the beginning of metaphase, specialized protein complexes called kinetochores mature on each centromere and attach to some of the spindle microtubules which are then called kinetochore microtubules.

The kinetochore microtubules align the chromosomes in one plane halfway between the spindle poles. Each chromosome is held in tension at the metaphase plate by the paired kinetochore and their associated microtubules, which are attached to opposite poles of the spindle Assembly of the metaphase spindle requires two types of events: Attachment of spindle microtubules to the poles and captured the chromosomes by kinetochore microtubules.

A kinetochore contacts the side of a microtubule and then slides along the microtubule to the (+) end in a process that may involve kinesins on the kinetochore. The kinetochore caps the (+) end of the microtubule. A combination of microtubule motor proteins at the kinetochore and microtubule dynamics at the (+) end of kinetochore microtubules is thought to position the chromosomes equally between the two spindle poles.

Anaphase

It is the shortest stage of mitosis. During Anaphase an enzyme called saparase degrades the multiprotien complex called cohesins which held together the sister chromatids at their centromeres.

The centromeres divide, and the sister chromatids of each chromosome are pulled apart or 'disjoin' - and move to the opposite ends of the cell; the kinetochores are pulled by kinetochore spindle fibres and are assembled at the centrosomes. The separated sister chromatids are now referred to as daughter chromosomes.

All of the newly separated chromosomes move at the speed, typically about 1mm per minute.(It is the alignment and separation in metaphase and anaphase that is important in ensuring that each daughter cell receives a copy of every chromosome.)

Anaphase can be divided into two distinct stages anaphase A and anaphase B (early and late anaphases); anaphase A is characterized by shortening of kinetochore spindle fibres which pulls the chromosome towards the pole.

On the other hand, during anaphase B the two poles move farther apart. It happens as a result of spindle elongation which occurs due to sliding of polar microtubules past one another and pulling forces exerted by astral microtubules.

Telophase

It is the final stage of mitosis. The end of the polar migration of the daughter chromosomes marks the beginning of the telophase; which in turn is terminated by the reorganization of two new nuclei and their entry into the G1 phase of interphase. In telophase the separate daughter chromosomes arrived at the poles and the kinetochore microtubules disappear.

The polar microtubules elongate still more, and a new nuclear envelope re-forms around each group of daughter chromosomes. The condensed chromatin expands once more, the nucleoli which had disappeared at prophase begin to reappear, and mitosis is at an end.