All processes in a cell are ultimately governed by the genetic make-up of that cell.

The genetic material in all organisms (prokaryotic and eukaryotic although not all viruses) is DNA (deoxyribonucleic acid).

The structure of this chemical determines which proteins are manufactured within the cell and hence controls the structure, and thus function, of the enzymes manufactured.

Note that DNA also determines the structure of other proteins made within the cell such as the structure of antibodies, structural proteins etc.

We will concentrate on the manufacture of enzymes since enzymes control many other processes within the cell.

Another nucleic acid RNA (ribonucleic acid) is involved in the process as an intermediary. (Some viruses do not contain DNA but, instead, use RNA as their genetic material)

In order to understand how protein structure is determined by DNA we must first study the structure of Nucleic Acids

Nucleic Acids are long chains of mononucleotides. Mononucleotides are themselves quite complex molecules made up of three components:

a pentose (5 carbon) sugar. In DNA the sugar is deoxyribose, in RNA the sugar is ribose

a nitrogenous (nitrogen-containing) base (there are 5 different nitrogenous bases found in nucleic acids falling into 2 groups - the purines and the pyrimidines)

phosphoric acid (which in ionised form is called phosphate)

For all of these 5 molecules you do NOT need to know the exact structures, it is sufficient to know that pyrimidines have ONE ring while purines have TWO rings.

Also you do not need to know their full names, the first letter abbreviation is enough.

The three components of a mononucleotide are joined by two condensation reactions - one between the phosphate and the sugar, one between the sugar and the nitrogenous base.

Note that a structure containing only the sugar and the base is known as a nucleoside - you don’t need to know this but you may occasionally see the word.

Where the sugar is deoxyribose the nucleotide is called a deoxyribonucleotide, where the sugar is ribose the nucleotide is called a ribonucleotide.

Note that ATP (the molecule which is used as an energy store in cells) is a ribonucleotide. NAD, NADP and coenzyme A (which will all be discussed later when considering biochemical pathways) are derivatives of nucleotides.

Joining a number of mononucleotides together forms a polynucleotide. Again this is achieved via a condensation reaction between the phosphate group of one nucleotide and the sugar residue of the next

This gives us a chain of nucleotides. However DNA has an additional level of structure and it is this which gives it its ability to act as the genetic material. Nuclear DNA is made up of 2 polynucleotide stands held together by hydrogen bonds.

The two strands of DNA are lined up with the bases pointing towards each other.

Note: the strands run in opposite directions i.e they are anti-parallel with one strand running 5' to 3' while the other runs 3' to 5'

The shape and chemical nature of the bases mean that (normally) they only pair up in particular ways specifically:

Guanine pairs with Cytosine

Adenine pairs with Thymine

Note each of these pairs is one purine bonding to one pyrimidine

Because one strand mirrors the other they are said to be complementary - knowledge of the sequence of one strand allows us to predict the sequence of the other strand

This results in the "ladder" structure of DNA with the repeating sugar-phosphate units forming the uprights and the base pairs forming the rungs.

The strands of DNA are not straight chains - each twists into a helix shape (think phone cable or helter skelter)

So the 2 strands together form a double helix

Extras..................

A simple animation illustrating the double helix is here

A rather longer one (that doesn't add a great deal of information) is here

Want to watch a space-filling model of DNA spinning around (......and around.....and around?) Click here

If you'd prefer to watch a ball and stick model rotating then click here

Cell replication is shown below. One cell divides to become two cells each new cell being identical to the other and to the mother cell

DNA is the genetic material of cells; it provides the genes which determine the characteristics of the organism.

But: genetic information must be passed from parent cell to daughter cell. How does the structure of DNA provide a mechanism for this?

What happens is that each daughter cell receives an exact copy of the mother cell’s DNA. So the DNA in the mother cell must replicate (be copied) before the daughter cells can be formed, i.e. a DNA molecule in the mother cell must replicate to produce two DNA molecules, one for each new cell.

The mechanism by which DNA can copy itself exactly is called semi-conservative replication. The two strands of a DNA molecule first separate, then each acts as a template for the synthesis of a new strand. A strand is able to act as a template because of the specific nature of the base pairs.

The process of cell replication is enzyme-controlled.

DNA Polymerase (DNA Pol) attaches to the DNA molecule and breaks the hydrogen bonds between the bases causing the two strands to separate (often described as "unzipping" the molecule). This makes unpaired bases available to act as templates.

DNA Polymerase also catalyses the polymerisation of the new strands of DNA. However DNA Pol can only synthesise new strands in the 5' to 3' direction, NOT in the 3' to 5' direction

For the 3' to 5' strand DNA Pol is unable to synthesise the whole strand in one go, instead it makes many short strands in the 5' to 3' direction.

DNA Ligase joins (ligates) these short strands together to make a complete molecule

As an aside. The process of new strand synthesis does not, as might be imagined, start at one end and continue to the other end as this would take too long. Instead synthesis begins at numerous points along the molecule, the various subsections being joined together on completion.

So DNA is the genetic material and implicit in its chemical structure is a means of producing exact copies of itself allowing for the production of new identical cells. But what are genes and how are they expressed?

Extras..................

A simple animation but showing the replication process in greater detail than necessary for A level can be found here

Genes and the Genetic Code

A gene is defined as "the sequence of nucleotide pairs along a DNA molecule that codes for an RNA or polypeptide product"

To give some context:

the human genome (the total amount of genetic material in a cell) is divided up into 46 molecules of DNA (each called a chromosome)

the total number of base pairs in these 46 molecules is 3,000,000,000 (3 billion). This amount of DNA would stretch out to one metre in length; i.e. each cell in the human body contains one metre of DNA 

there are believed to be 30,000 - 35,000 genes present (i.e. 30,000 - 35,000 regions that code for an RNA or polypeptide product

the average length of a single human gene is 3000 base pairs. The largest human gene is 2.4 million base pairs

It would take about 2 minutes to transcribe the average sized gene

There are millions of ribosomes in a single cell. A  eukaryotic ribosome can add 2 amino acids to the growing chain every second, so an average polypeptide is translated in well under 30 minutes; prokaryotic ribosomes are even faster at 20 amino acids per second

So a gene codes for a polypeptide i.e. the sequence of bases in DNA determines the sequence of amino acids in a polypeptide. How?

There are only 4 bases in DNA (GCAT) but there are 20 amino acids found in polypeptides.

If 1 base coded for an amino acid there would be a maximum of 4 different amino acids that could be coded for - not enough

If 2 bases coded for an amino acid there would be a maximum of 16 different amino acids that could be coded for - still not enough

If 3 bases coded for an amino acid there would be a maximum of 64 different amino acids that could be coded for - more than enough.

The 3 base hypothesis is now accepted and is called the base triplet hypothesis. A sequence of 3 bases (a triplet) is called a codon.

Since DNA never leaves the nucleus (because it is too large to fit through the nuclear pores) but protein synthesis takes place on ribosomes located elsewhere in the cell there must be a means of carrying the information stored in the DNA (i.e. the sequence of bases in a gene) from the nucleus to the ribsome.

A molecule known as messenger RNA (mRNA) is synthesised using the gene sequence as a template (very similar to DNA replication). The mRNA is complementary to the sequence of the gene.

Note that RNA does not contain Thymine instead it contains Uracil. So the complementary base pairs when DNA is used as a template for RNA are

This can be remembered as GoCAU

The particular amino acid coded for by each triplet codon has been determined experimentally and tables of this information are readily available.

Note some tables show the DNA codon while some show the mRNA codon.

Inspection of a codon : amino acid table will show two important points.

Many amino acids are coded for by more than one triplet codon. For this reason the genetic code is said to be degenerate

Some triplets codons are called stop codons: when protein synthesis reaches one of these codons it ceases

An animated exercise involving making an mRNA strand and then making the corresponding protein using the universal code can be found here

The molecules and structures involved:

You have already studied

DNA

polypeptides

Ribosomes

You need to know about:

messenger RNA (mRNA)

transfer RNA (tRNA)

The subunit of RNA molecules is the ribonucleotide made up of ribose, phosphate and one of four nitrogenous bases (GCA or U)

It is important you know the differences between RNA and DNA. Already mentioned are the different sugar component and the difference between the bases present.

In addition RNA is single stranded. (Though some RNA molecules have regions where the strand folds back on itself and base-pairing occurs between two parallel regions).

messenger RNA

acts as an intermediary between DNA and proteins. The information stored in the base sequence of DNA is passed to mRNA and the mRNA acts as a guide to the amino acid sequence of proteins

mRNA travels from the nucleus (where the DNA is) to the cytoplasm (where protein synthesis occurs

is only found in single-stranded form

transfer RNA

present in the cytoplasm

binds to an amino acid

has regions of base-pairing

has an anti-codon region

tRNA is specific for a particular amino acid i.e. there are 20 different tRNAs, one for each amino acid. At one end of the molecule the appropriate amino acid binds. At the other end is a 3 base sequence which is complementary to the triplet codon on mRNA. This region is called the anti-codon.

tRNA binds to its amino acid in the cytoplasm and transfers it to the site of protein synthesis, the ribosome

ribosomal RNA

the third form of RNA is rRNA

it is a component of ribosomes so is involved in protein synthesis but you do not need to know anything more specific about it.

 

Now that you have met all of the molecules involved here is a diagram of the whole process

You will see there are two processes involved: transcription and translation

occurs in the nucleus

is synthesis of a molecule of RNA which is complementary to the gene sequence on DNA

involves the enzyme RNA Polymerase (RNA Pol)

RNA Pol attaches to double stranded DNA (dsDNA)

it attaches at a "start" codon. The start codon is the codon for methionine

it breaks the hydrogen bonds holding the two strands together causing the DNA to unwind (i.e. lose its helical shape)

the enzyme catalyses the synthesis of a molecule of RNA using one of the DNA strands (called the coding strand) as a template. The RNA strand is thus complementary to the coding strand and has an equivalent sequence to the non-coding strand. Different authorities have different names for the two strands and differ in which strand they consider to be the gene sequence. For exam purposes you will probably be given the coding sequence but it should be obvious what is expected however it is presented

Once synthesised the mRNA molecule is modified because not all of the gene sequence is represented in the final protein molecule.

These extra regions of DNA, or intervening sequences, are called introns

The regions that are expressed are called exons

The lengths of mRNA synthesised against the intron sequences are cut out and the parts that are left are spliced together

Additional reading: you may want to study the 5'-cap and 3' Poly-A tail added to mRNA at this stage. You do not need this information for exam purposes but it could make the difference between that A you want and some other mark.

Extras...................

A very good animation of transcription can be found here

An animation showing transcription and translation (along with descriptions of some of the experiments which elucidated the processes) is here

A simple animation of transcription can be found here. This is only one of many similar animations - try a search on transcription + animation

An animated exercise involving making an mRNA strand and then making the corresponding protein can be found here

the mRNA travels through the nuclear pore and binds to a ribosome

when mRNA is attached to a ribosome two codons on the mRNA are expopsed.

the tRNAs specific for these codons hydrogen bond to the mRNA and the amino acids bound to them are joined together. The enzyme which catalyses this condensation reaction is called peptidyl transferase

when the bond is formed the amino acid becomes detached from its tRNA and the tRNA leaves the ribosome ready to pick up another amino acid.

once the bond is formed the ribosome physically moves along the mRNA one codon length exposing another codon ready for its tRNA.

the amino acid chain thus produced (i.e. incomplete, still associated with a ribosome) is said to be nascent, or growing

Amino acids are added at a rate of 15 per minute

more than one ribosome can be attached to a molecule of mRNA (forming a complex known as a polysome) at a time so multiple polypeptides can be synthesised simultaneously from one mRNA

Translation ceases when a stop codon is reached. There is no tRNA specific for this codon and the ribosome "falls off" the mRNA ending synthesis

Extras...........................

An excellent animation of translation can be found here

An animated exercise involving making an mRNA strand and then making the corresponding protein can be found here

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