DNA double helix mitosis meiosis

DNA double helix Crick, Watson, Wilkins and Franklin

BIOLOGY
DNA

Structure of an organism

DNA is the common name for Deoxyribonucleic acid, the chemical of life. This nucleic acid is made of long chains of nucleotides, which are complex molecules present in the nucleus of all cellular forms of life and many viruses, and in the cytoplasm of single celled bacteria, which do not have a nucleus. DNA carries along its length a series of coded chemicals called genes, which give instructions for passing on hereditary characteristics, such as leaf shape, claw length, hair or eye colour as well as susceptibility to some diseases.

Each nucleotide consists of:

1. A sugar with five carbon atoms, either:
(a) Deoxyribose, a sugar used by DNA, with a hydrogen atom attached to its carbon atom number 2' (referred to as the two prime carbon atom; ' or prime is the first sub division or symbol marking it).
or
(b) Ribose, a sugar used by RNA (a single strand ribonucleic acid which translates the coded messages) and with a hydroxyl group atom attached to the 2' carbon.

2. One of three phosphates with four oxygen atoms, two of which are negatively charged:
Attached to the 5' carbon atom of the deoxyribose sugar and covalently to the 3' of the next. (One electron from each atom joins the two together).

3. A base:
One of four kinds of nucleobases (a base). A base, is a ring structure containing nitrogen and is attached to the 1' carbon atom of the deoxyribose sugar.
The four bases used by DNA are:
Adenine (A) and Guanine (G) which are purines. Thymine (T) and Cytosine (C) which are pyrimidines.

The four bases used by RNA are:
Adenine (A) and Guanine (G) which are purines. Uracil (U) and Cytosine (C) which are pyrimidines.

DNA composition

Pairs of DNA molecules, each only one millionth of a millimetre long, containing chromosomes with encoded genes along them take the shape of a right handed twisting double helix, an elegantly simple structure that resembles gently twisted ladders. The side rails of the ladder are made of alternating molecules of deoxyribose sugar and phosphates, going down one side of the strand and up the other. The rungs on the inside consist of hydrogen bonds, joining the bases in a particular sequence across the strands. The bonds are antiparallel, with a spare phosphate at opposite ends of each strand. The hydrogen on a base is attracted to the carbon on a sugar, whereas phosphates, being negatively charged, would repel each other if they were opposite each other on the inside of the helix.

DNA phosphate

DNA Deoxyribose sugar

DNA section showing gene ACT on the descending strand and gene AGT on the ascending strand

DNA strands, when viewed through an electron microscope, are read from the 5' carbon atom to the 3' carbon atom on the descending strand, and 3' to 5' on the ascending strand. Each chromosome is a very long piece of DNA with many genes encoded along its length. It is twisted, looped and wound round itself, attached to a protein to maintain its shape, then two sets are twisted into the double helix shape. The human chromosome number 1 is 10 micrometres long, but has 7 cms of DNA inside it.

There are three forms of DNA:
1. The A or dehydrated (dry) form, used in crystallography. This twists in a right handed helix and has 11 base pairs per turn.
2. The B or wet form, 2 nanometres wide, twisting in a right handed helix, with 10 base pairs per turn.
3. The Z form, similar to B but twisting in a left handed helix. Sometimes created by mutation.

By understanding the structure of the molecule clues can be gained about how it functions. Because each base within a rung of the DNA ladder is always paired with the same complimentary base, one half of the molecule can serve as a template for the construction of the other half. The length of DNA in a single cell is approximately 1.7 metres wound tightly round itself. Each cell in the body has a similar length of DNA and all the DNA in the body would reach to the moon and back 6000 times.

Double Helix

This diagram shows the two phosphate-sugar chains held together by the pairs of bases forming the rungs of the DNA ladder. The vertical line shows the axis.

The nucleotides in DNA contain the bases adenine (A), guanine (G), cytosine (C) and thymine (T). In nature genetic encoding is carried out with these four building blocks. Each base will only pair up with one other base on the strand by means of hydrogen bonds; adenine with thymine or cytosine with guanine. There are three types of hydrogen bonds: O-H-N, O-H-O, N-H-N. (O is oxygen, N is nitrogen, H is hydrogen). The bases are attracted because the hydrogen atom on one base is attracted to either the oxygen or nitrogen atom on the other, thus allowing hydrogen bonds to be formed. Two hydrogen bonds join A+T and T+A; three hydrogen bonds join C+G and G+C. Thus the sequence of the bases along each single strand can be deduced from that of its partner. This complimentary pairing explains how identical copies of parental DNA can be passed on to two daughter cells.

Thymine and Adenine

Cytosine and Guanine

During cell division, the DNA helix chemically “unzips”, and two new strands are formed from the half-ladder templates. The precise sequence of nucleotides (sugar, phosphate and base) in the DNA ladder directs the manufacture of proteins and determines the identity of a living organism and makes the cells work. Each type of cell, such as kidney or skin, will only use the specific instructions needed for it to function.

Each chromosome is a very long molecule of DNA with many genes along its length, providing a set of instructions for making an organism. These instructions are called the genome. The number of bases can vary from a thousand to a million. A sequence of three bases, such as A C T, C A G, T T T, along the strand makes up a gene, each group of three represents the code for one of twenty amino acids, which in due course forms part of a protein molecule, which provides the structure of cells and tissues. Each group of three is a codon. There are 64 known codons, with 3 stop or nonsense codons marking the end of the sequence. It is estimated that 3 billion base pairs of A T C G make up the human genome, less than 5% being genes, the function of the rest is not known at present. Each individual has a different arrangement of these letters in their genetic code, thus it is very unlikely that two humans or organisms will be exactly identical. The purpose of more than 30,000 genes has so far been established.

Each cell in the human body contains two complete sets of 22 numbered chromosomes plus X and Y, making 46 in total. The arrangement of the chromosomes in a cell is called a karotype. The largest chromosome is number 1 and the smallest is number 22, plus sex chromosomes X and Y, females having two X and males X and Y. In the laboratory white blood cells are generally used to study chromosomes, which are separated using enzymes. When stained they are seen to have a waist like band at the centre, called a centromere, and distinctive black and white bands showing the different amounts of bases A and T compared with bases G and C in each and so they can be identified. Chromosomes are divided at the centromere into a long and short arm, the short arm being called petit or p and the long arm being called q. The regions on the chromosome are numbered from the centromere for identification purposes. Regions are specifically numbered up or down from the centromere, so a specific part of a chromosome can be pinpointed using a code.

Diagrammatical example of a pair of chromosomes

For example: A female with an abnormality on the long arm of chromosome 9 would be written as XX9q12.1

XX represents female
9 is the chromosome number
q is the long arm
12.1 is the region

Whereas a male with the same abnormality would be written as XY9q12.1 as XY represents male.

XY represents male
9 is the chromosome number
q is the long arm
12.1 is the region

If a gene is missing from the short arm of chromosome 6, it would be identified as 6p-.

6 is the chromosome number
p is the short arm
- means a gene is missing

Each chromosome has a particular sequence of genes. In humans chromosome number 11 has 2093 genes, with 134,978,784 bases. Chromosome number 22 has 288 genes, with 49,476,972 bases.

Different species have a different number of chromosomes.

	Human - 46
Fruit fly - 8	Fern - approx. 1200	Dog - 78
Earthworm - 36	Chicken - 78	Carp - 104

The reproductive cells, the egg and the sperm, each contain only 23 single chromosomes, formed by the process of meiosis. During reproduction these join together to form a new cell with one set of chromosomes from each parent. In this way, each offspring has characteristics from each parent, but is not identical to either. The DNA in this cell then splits and replicates millions of times by the process of mitosis until a viable new offspring is formed. One human chromosome contains 150 x 10⁶ nucleotide pairs and these are copied at 50 base pairs per second. Replication can occur at several points on the chromosome, thus the whole process takes about one hour. If replication took place at only one point it would take a month.

New nucleotides are constantly being made within the cell nucleus. During replication the strand splits at several places where the G C pairs are weakest connected by two hydrogen bonds. When a cell is ready to divide the enzyme DNA helicase untwists the helix to form a Y shape, called a replication fork. The enzyme DNA polymerase travels from the join of the replication fork down the leading strand in the 3' to 5' direction, reading the nucleotide sequence. To maintain the antiparallel form of the DNA, with a phosphate at the 5' end, the DNA polymerase then attaches new, corresponding nucleotides to the leading strand in the 5' to 3' direction. New nucleotides cannot be attached at the 3' end of the second or lagging strand, as this would upset the antiparallel form leaving a phosphate at the wrong end of the strand. Sections of DNA called Okazaki fragments are therefore made in the nucleus of the cell to combat this. When long enough sections have been made they become attached to each other and to the lagging strand in the 5' to 3' direction by the enzyme DNA ligase. Two new strands of DNA have now been assembled.

Diagrammatical example of replication

Mitosis is the process by which most cells in the human body are replicated. During replication a duplicate is made for each chromosome, doubling the number in the cell to 92, so they become X shaped by joining at the central waist like area called the centromere. This is attached to microtubules which, during cell division, pull the chromosomes to opposite ends of the cell. The cell divides in the middle having created two identical daughter cells each with 46 chromosomes.

Diagrammatical example of mitosis

Meiosis is the process of replication by which egg cells are produced in the female ovaries and sperm cells are produced in the male testes. This involves two sets of cell division. The first part of the process is similar to mitosis as stem cells produce two identical cells, each with 46 chromosomes. However, some of these then split again, without replicating the chromosomes, resulting in four cells each with only 23 chromosomes. During meiosis the chromosomes crossover twice to produce different gene combinations in each egg or sperm and this process takes three weeks to complete. In human males 200,000,000 sperm are made each day, but in females only one viable ovum is made each month.

Diagrammatical example of meiosis

Also in the nucleus of the cell is the chemical RNA (Ribonucleic acid) composed of adenine, guanine, uracil and cytosine. RNA is divided into several classes, each having a different function within the cell. During the making of a protein a unit of three coded bases on the DNA unwinds and passes the code on to a messenger molecule of RNA. Carrying the copied code this then moves out of the nucleus into the cytoplasm of the cell where it is copied into an amino acid and this joins with more amino acids to form a protein.

Proteins are polymers which can be composed of up to 20 different amino acids. These are arranged in a string along the protein and can be in a complex pattern. The sequence of the amino acids and the function of the protein is determined by the genetic code. There are many different types of protein performing tasks such as:

Storage, transport, hormonal, receptor, contractive, defensive, enzymatic.

Thus we see that all organisms are made up of many chemicals which, when organised, have specific ways of working together, as in DNA. These chemicals came from the primordial swamps and are constantly evolving. What else is there to discover? © GMH BA

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