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The DNA molecule is immensely long and thin. In
fact there are two metres of DNA neatly packaged into
chromosomes and every cell has the full amount.
Cells are busy places, constantly transforming
food into energy, removing rubbish, dividing and
growing. The DNA runs it all. But the magic of DNA is that it also has the power
to determine what we inherit from our parents. DNA
passes on the information on how to build a body from
one generation to the next. But how?
In 1953, the Englishman Francis Crick and the American
James Watson realised that it had something to do with
the structure of the molecule itself. When at Cambridge
University, they began building models, trying to figure
out how the atoms of DNA were arranged. Many researchers
were hot on the trail of DNA, but Watson and Crick
got there first; they were at the right place at the
right time.
They knew that an X-ray of a DNA crystal would give
them an idea of the general shape of the molecule.
Maurice Wilkins and Rosalind Franklin at University
College, London, had used this technique and found
that DNA had a helical structure – like a corkscrew.
With the help of one of these photographs, Watson and
Crick finally succeeded in building a model that not
only fitted all the evidence but also explained how
DNA could be the molecule of inheritance. That model
was the double helix.
Watson and Crick succeeded because they worked out
that the four units called ‘bases’ that
make up DNA could fit together like jigsaw pieces.
For their discovery, Watson, Crick and Wilkins earned
the prestigious Nobel prize in 1962. Sadly, Franklin
died before the prize was awarded, and this prize is
not given after death.
Looking at their model, it seems simple enough today,
but it is perhaps the major scientific discovery of
the 20th century. To visualise the DNA molecule, first
try to imagine a ladder, then twist it into a spiral.
The sides are made out of sugar and phosphate molecules
stacked one on top of the other. The rungs are formed
by bases – large molecules that contain the genetic
information. These bases are the familiar DNA ‘letters’ known
by their initials, A (adenine), C (cytosine), G (guanine)
and T (thymine).
These four ‘letters’ are very fussy as
to whom they pair off with. Adenine and guanine are
large and thymine and cytosine are small. In the DNA
molecule, A will join to T (but not to C) and G will
join to C (but not to T). If you look down one of the
DNA chains, the bases can come in any order, but they
always bond strictly with a matching base on the opposite
chain. These ‘complementary’ pairs fit
like the pieces in a jigsaw, holding the ladder together.
Because the letters work as a code. The sequence of
A, C, T and G along the DNA molecule form a coded instruction
which the cell uses to make proteins.
Proteins are the molecules that do most of the work
in a living body and they have different roles. Some
form structures such as hair or skin. Others, such
as enzymes, control all the building up and breaking
down that goes on inside cells; others are hormones
such as insulin, which tells the body to store energy
after a meal.
Proteins are made up of chains of small molecules
called amino acids. There are 20 amino acids in total,
which seems hardly enough to produce the huge variety
of proteins you need to build an organism. But because
the amino acids can be arranged in any order or length,
there are a staggering amount of combinations – too
many to even imagine!
For a protein, the order of its amino acids is crucial.
The sequence of amino acids will determine how it will
fold into a 3-D shape. That shape will in turn determine
its structure and properties, and what other molecules
it will interact with. The DNA must store that order.
Somehow, the sequence of bases along the DNA must specify
the order in which amino acids will be joined together
to form a protein. This is the so-called genetic code.
Cracking the genetic code wasn’t easy. Labs
around the world struggled for more than a decade after
Watson and Crick’s discovery to work out that
it takes a three-letter DNA ‘word’ (also
called a codon) to represent one amino acid. Because
there are actually four DNA letters, it is possible
to make up 64 codons. Because there are only 20 amino
acids, this leaves enough scope for some amino acids
to have alternative codes, and for a few extra instructions
such as ‘stop’ and ‘start’.
Genes are the part
of DNA that actually contains the information to
make a protein. So if you take any stretch of DNA,
you will
find many different genes along it, each making a
different protein. Estimates suggest that there are
about 30,000–40,000
genes in the human
genome.
Together, these genes form the structures of your
body and are responsible for making you look and
function like you do.
To understand how the body works at the most basic
level, we need to read the entire message of an organism,
its genome. This is what is known as sequencing: it
involves reading the nucleotide bases as they occur
along the DNA molecule.
In 1977, the biochemist Fred Sanger of Cambridge University
was the first to read the full genetic message of an
organism – a tiny virus with about 5000 DNA letters.
It was a painstaking process, but the sequencing tool
Sanger devised became the basis of modern methods.
Today, using the same sequencing principle but with
machines and powerful computers, the human sequence
has been read. In June 2001, the first draft of the
complete human sequence was published in what has been
described as one of science’s crowning achievements.
But although we now know the DNA letters in ‘the
book of life’, the job is not over yet. It has
only just begun.
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