Deoxyribonucleotides

Deoxyribonucleotides consist of three molecules:

• deoxyribose
  
• phosphate
  
• nitrogenous base.

The bases are those elements of the double helix that carry the genetic code. They are arranged in different sequences along the deoxyribose–phosphate strands of the double helix. Each deoxyribonucleotide comprises three parts: a nitrogenous base, a deoxyribose sugar, and one phosphate group.

Bases

There are four different bases found in DNA, namely:

• adenine (A)
  
• thymine (T)
  
• guanine (G)
  
• cytosine (C)

The order in which the bases are organised along the length of the DNA molecule provides the variation that allows for the storage of genetic information.

Look again at the drawing of the double helix; each strand carries different bases. These bases join together and make the molecule stable. However, these bases do not just pair off haphazardly; they can only pair up with bases that match them so that they will fit together (like jigsaw pieces). Because of this, the bases are limited as to which other base they will pair with, and there is a golden rule to remember with this pairing:

• adenine (A) always pairs with thymine (T)
  
• guanine (G) always pairs with cytosine (C)

So, if one half of the DNA has a base sequence

then the opposite side of the DNA will always have the complementary base sequence

The bases join together by means of hydrogen/polar bonding, and the individual bases are connected to the deoxyribose of the strands by means of covalent bonds. This is important because hydrogen bonds are not as strong as covalent bonds, and thus can separate more easily. The importance of this will become apparent when DNA replication and protein synthesis are discussed (Jorde et al., 2015).

Chromosomes

A chromosome does not just consist of DNA. Rather, the nuclear DNA (known as nucleic acid) of cells is combined with protein molecules (known as histones). Together, the DNA and histones make up the nucleosomes contained within the cell nucleus. This nucleic acid–histone complex is known as chromatin.

If we unravelled all the chromatin from every cell in a human adult body, its length would be equivalent to nearly 70 trips from the Earth to the Sun and back, and, on average, a single human chromosome consists of a DNA molecule that is almost 5 cm in length (Cell, 1966). We only manage to package that amount of DNA and histone molecules in our bodies because they are so neatly folded that they fit into each cell of the body. The chromatin cannot just be pushed into the cell haphazardly – it would never fit and there would be a high possibility of things going wrong (Vickers, 2011). Consequently, the chromosomes twist on one another before being arranged into loops and superloops, until they assume the shape that is recognisable as a chromosome – i.e., the X‐shape that can be seen in a human cell (Fig. 2.3) (Jorde et al., 2015).

Each chromosome is made up of two chromatids joined by a centromere to make an ‘X’ shape. Each half of the chromosome is a chromatid, and where they join near the top of the X, that is the centromere (Fig. 2.3).

In most humans, each nucleated body cell (i.e., each body cell with a nucleus) has 46 chromosomes, arranged in 23 pairs. Of those 23 pairs, one pair determines the gender of the person. These sex chromosomes are designated as X and Y chromosomes (all the others have numbers from 1 to 22), as can be seen in Fig. 2.4.

• Females have a matched homologous (similar) pair of X chromosomes, i.e., XX.
  
• Males have an unmatched heterologous (different) pair – one X and one Y chromosome.
  
• The remaining 22 pairs of chromosomes are known as autosomes. In biology, the word ‘some’ means body, so autosome means ‘self body’.
  
• Autosomes determine physical/body characteristics – in other words, all characteristics of a person that are not connected with gender.

One of each pair of a chromosome that we inherit comes from our mother and one comes from our father, and the position a gene occupies on a chromosome is called a locus. There are different loci for colour, height, hair, etc. Think of the locus as the address of that particular gene on Chromosome Street – just like your address signifies that that is where you live.

Genes that occupy corresponding loci and code for the same characteristic are called alleles. Alleles are found at the same place in each of the two corresponding chromatids, and an allele determines an alternative form of the same characteristic, whether it be hair colour, eye colour, or propensity for certain diseases, and so forth.

Example:

Look at the colour of a person’s hair – the gene that determines hair colour is found at the same place on each of the two chromatids of one particular chromosome. One gene will come from the father and the other from the mother. If parents of a child have different coloured hair from each other – perhaps the mother has red hair and the father brown hair, the child may have red or brown hair, depending upon factors that will be discussed later in this chapter.

This principle applies to each of a person’s characteristics, for example, eye colour, or height. A person with a pair of identical alleles for a particular gene locus is said to be homozygous for that gene, whilst someone with a dissimilar pair is said to be heterozygous for that gene.

There are two other very important facts to mention about genes: some genes are ‘recessive’ and some genes are ‘dominant’.

• A dominant gene is one that exerts its effect when it is present on only one of the chromosomes. (The name ‘genotype’ is given to the type of genes found in the body, whilst the name ‘phenotype’ is given to any gene that is manifested in the person.)
  
• A recessive gene (genotype), however, has to be present on both inherited chromosomes in order to manifest itself (phenotype).

This is a very important concept to grasp because of the significance that it brings to bear on hereditary disorders.

Protein synthesis

Synthesis means ‘production’, for example, the production of protein from raw materials. All the genetic instructions for making proteins are found in DNA, but in order to synthesise these proteins, the genetic information encoded in the DNA has first to be translated into RNA and then into a protein.

Initially, all of the genetic information in a region of DNA has to be copied in order to produce a specific molecule of RNA (ribonucleic acid).

Then, through a complex series of procedures, the information contained in RNA is translated into a corresponding specific sequence of amino acids in a newly produced protein molecule.

There are two parts to this procedure: transcription and translation.

Transcription

In transcription, the DNA has to be transcribed into RNA because protein cannot be synthesised (produced) directly from DNA. By using a specific portion of the cell’s DNA as a template, the genetic information stored in the sequence of bases of that DNA is rewritten so that the same information appears in the bases of RNA. To do this, the two strands of the DNA first have to separate (Fig. 2.5), and the bases that are attached to each strand then pair up with bases that are attached to strands of RNA.

As with the two strands of DNA, the bases of DNA can only join up with a specific base of mRNA. As with DNA, guanine can only join up with cytosine in RNA, but in RNA, the adenine in DNA can only join to uracil (U) in the RNA, because there is no thymine in RNA:

For example,

• if DNA has a base sequence AGGCAGTGC
  
• then mRNA will have a complementary base sequence UCCGUCACG

Fig. 2.5 shows how the DNA separates and makes more DNA. This same process occurs during transcription, except that the new strand with its bases is RNA rather than DNA.

Thus, DNA acts as a template for mRNA (Vickers, 2011). However, in addition to serving as the template for the synthesis of mRNA, DNA also synthesises two other kinds of RNA: rRNA and tRNA.

• rRNA = ribosomal RNA – rRNA, together with ribosomal proteins, makes up the ribosomes.
  
• tRNA = transfer RNA – this is responsible for matching the code of the mRNA with amino acids.

Once ready, mRNA, rRNA and tRNA leave the nucleus of the cell and in the cytoplasm of the cell commence the next step in protein synthesis, namely translation (Fig. 2.6).

Missense mutation

This occurs when there is a change in one DNA base pair, which leads to the replacement of one amino acid for another in the protein for which that gene is an important component.

If, in the above gene sequence, one of the nucleotides is altered so that the sequence becomes:

Then that change in the sequence causes that triplet to code for a different amino acid, and hence a different protein is formed. So the gene does not make sense – hence ‘missense’.

An example of a genetic disorder caused by a missense mutation is sickle cell anaemia.

Nonsense mutation

When a nonsense mutation occurs, there is also a change in one DNA pair. However, rather than substituting one DNA base pair for another, this type of mutation sends a signal for the sequence to be prematurely concluded. This leads to a shortened protein which may, or may not, function properly, or even may not function at all.

If, in the above gene sequence, one of the nucleotides is altered so that the sequence becomes:

Then the sequence for this gene is altered in such a way that the production of the protein is terminated prematurely. The subsequent resulting shortened protein may not function as it should or may not even function at all.

Cystic fibrosis is an example of a disease caused by a nonsense mutation.

Deletion

A deletion mutation occurs when the numbers of DNA bases are reduced by the removal of a piece of DNA. The resultant problems may occur as a result of just one or two base pairs within a gene or the removal of a complete gene or even several genes. When this occurs, the function of the resulting protein (or proteins) may be altered.

22q11.2 deletion syndrome is one such disease caused by this mutation. It is caused by the deletion of just a small section of chromosome 22. There are many health problems with this deletion mutation including cleft palate, heart defects, autoimmune disorders, to name just a few. The symptoms vary considerably from child to child, but they can also be accompanied by learning disabilities and mental illness.

Other problems caused by genes occur following:

• Insertion – where the number of DNA bases are increased by adding a piece of DNA to the sequence. Examples of diseases caused by this mutation include Fragile X syndrome and Huntington’s disease.
  
• Frameshift mutation – this is a mutation that is caused by an insertion or deletion of a nucleotide, which causes a shift in the translational reading frame (the groups of three nucleotide bases that each code for one amino acid). This results in the moving of one nucleotide forward or back within one triplet, so that the resultant triplets are out of synchronisation. This usually results in a non‐functioning protein – hence the body is missing that protein. Crohn’s disease and Tay–Sachs disease are just two of the diseases caused by frameshift mutations, which are also a factor in some cancers.
  
• Duplication – sometimes a mutation can occur when a piece of DNA is copied wrongly, so that there is more than one copy of it. This can lead to altered functioning in the resulting protein. One such disease caused as a result of duplication is Charcot–Marie–Tooth disease type 1, which leads to disorders of the peripheral nervous system, which causes progressive loss of muscle tissue and loss of touch sensation.