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Molecular biology is a comparatively young field
of science; it is still maturing. Even so, describing the discoveries
made by molecular biologists would take far
more space than we have here, so we’ll just have a look at
the fundamental discoveries.
Deoxyribonucleic acid (DNA) was
discovered in salmon sperm by Johann Friedrich Miescher in 1869,
but was thought to be too simple to act as the repository of genetic
information: DNA is made up of only four nucleotides
– adenine (A), guanine (G), cytosine (C) and thymine (T) –
which consist of a phosphate group, a sugar (deoxyribose) and a
base. Proteins
were thought to be of prime importance, as the twenty natural amino
acids could create a code sufficiently complex for life.
However, scientists failed to realise that DNA molecules were longer
than just the four bases bonded together, and that the sequence
of DNA nucleotides varied, and was in fact the code!
Following the work of Griffith in 1928, showing
that extracted DNA could make bacteria virulent, further work suggested
that DNA was in fact the genetic material. Watson and Crick created
a model for the structure of DNA in 1953, based on Rosalind Franklin’s
X-ray diffraction pictures.
| The model shows
two strands of nucleotides intertwined with each other in
a double helix. The strands interact as a
result of hydrogen bonding. Sequential nucleotides
are bound by covalent bonds between the phosphate attached
to the fifth carbon (5’ or 5-prime) in the sugar of
the second nucleotide, and the third carbon of the sugar (3’
or 3-prime) in the first nucleotide. A chain can then be built
from 5’ to 3’ based on phosphodiester
bonds. The sequence in the other chain runs in the opposite
direction and is said to be antiparallel:
Interactions between opposite bases on the
two strands are highly specific and depend on the hydrogen
bonding pattern caused by their atomic structure.
A always pairs with T, and G with C. This forms the basis
of DNA’s ability to store genetic information. |
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Every time a cell divides, it must make copies of
its DNA. This is done in a semiconservative manner.
Replication occurs using an enzyme called DNA polymerase
which uses one strand of DNA as a 'template' to form a copy of the
opposing strand. Nucleotides are added to each of the original strands,
forming two DNA molecules, one going to each daughter cell. This
process is very accurate, and mistakes (causing mutation,
or a heritable change in the genetic information) are rare.
At any one time, only a fraction of the sensible
DNA (i.e DNA that lies in genes) is "awake"
in any one cell. So how does the cell know which DNA needs to be
active?
The answer lies in the sequence. If we compare
a short stretch of DNA to the paragraph below we can see how this
happens:
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sfdsgrweaffa IMPORTANT!!!: moqlahgoswyfongaontiwlsai
READ THIS: ialaconpae. DNA is often repeated
and contains useless ignspfakssgan sequence between genes. DNA
is often repeated and contains useless ignspfakssgan sequence
between genes. Sensible DNA within genes can be interrupted
(ngwngiqoi) with (fehsghsdao) gibberish. SSSSSSSSS. Sequence
may be inverted. .detrevni eb yam ecneuqeS Chemical
tags may highlight DNA to be copied. Some DNA can have
more than one meaning two messages can be created. Sequences
show where genes start and stop. sabsgdobaslafboq |
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As you can see, the bold and exclamation marked
words (as well as the preceding text) draw our attention to the
paragraph, and our brains spot the patterns forming words and sentences,
and tend to ignore those that we don’t immediately recognize.
We are also using punctuation to tell us where the sentences start
and finish, and which clauses within a sentence are less important.
We can also interpret some sentences in more than one way, depending
on how we look at it. Modifications of the text also influence our
perception (we are immediately drawn to the red text, for instance),
and punctuation symbols promote the importance of a sentence.
DNA itself acts only as a set of instructions. It
is proteins that carry out the cell's day-to-day business, and in
order to make proteins the DNA needs a messenger that can transfer
these instructions to the protein-making apparatus of the cell.
This messenger is called messenger ribonucleic acid or
mRNA, and is a molecule similar to DNA except that it is
usually single stranded, has a different sugar, and T is replaced
with Uracil (U). The process of making mRNA from DNA is called transcription,
and works in a similar manner to DNA replication, as the two strands
of DNA are again separated and used to make (in this case) a single,
complementary strand of mRNA. Other genes may “switch on”
the gene that is to be transcribed, short promoter
sequences "upstream" of this gene allow the RNA polymerase
enzyme to bind to the template strand, and three bases (ATG) will
tell the enzyme exactly where to begin synthesising messenger ribonucleic
acid (mRNA) from the DNA template. The DNA is then copied in three
letter “words” called codons until
a stop codon (TAA, TAG or TGA) is reached. In the first draft of
mRNA (the primary transcript) intervening useless
DNA is left in, but subsequent edits remove this. The "spellchecked"
mRNA is then released from the nucleus (in the case of eukaryotes
such as fungi), and reaches the protein factories in the cytoplasm,
where translation occurs. (In prokaryotes such
as bacteria there is no nucleus, so that proteins can begin to be
made from the mRNA even while the other end of the mRNA strand is
still attached to the DNA).
Ribosomes are responsible for
"interpreting" the mRNA code and using it to assemble
amino acides into proteins. This is done using a second type of
RNA, transfer RNA or tRNA, which
recognizes the codons by base-pairing. tRNA molecules bind to specific
amino acids, through the activity of specific activating enzymes,
and also bind to a particular codon (or to one of several codons,
each of which will therefore code for the same amino acid). This
forms the basis of the genetic code which is largely universal.
The process begins when an "AUG" sequence on the mRNA
is recognised by the inititiation complex, which initiates the polypeptide
sequence with the amino acid methionine. When a
second tRNA molecule comes along to bind to the next three-letter
sequence, peptide bonds are formed between its amino acid and the
methionine already present, and the methionine is released from
its own tRNA. The "assembly line" moves onward one codon
at a time until the stop codon is reached.
The amino acid chain (or polypeptide)
is then released from the ribosome, and undergoes spontaneous chemical
interactions that give it its specific 3D shape or conformation.
Other proteins may modify and check the shape, or add sugars or
fats to the new protein. The protein can then be sorted by the palade
pathway in the Golgi apparatus to where
it is needed, either in the structure of the cell, outside the cell
(in the case of exoenzymes for example) or into
certain organelles. Once the protein has reached its target, it
can start performing its particular function, be it structural,
regulatory, catalytic or whatever.
To summarize, we shall track the changes made during
the expression of our DNA paragraph:
| DNA (English and nonsensical): |
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sfdsgrweaffa IMPORTANT!!!: moqlahgoswyfongaontiwlsai
READ THIS: ialaconpae. DNA is often repeated
and contains useless ignspfakssgan sequence between genes. DNA
is often repeated and contains useless ignspfakssgan sequence
between genes. Sensible DNA within genes can be interrupted
(ngwngiqoi) with (fehsghsdao) gibberrish. SSSSSSSSS. Sequence
may be inverted. .detrevni eb yam ecneuqeS Chemical
tags may highlight DNA to be copied. Some DNA can have
more than one meaning two messages can be created. Sequences
show where genes start and stop. Sabsgdobaslafboq |
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| mRNA primary transcript (Spellchecked
English): |
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DNA is often repeated and contains useless ignspfakssgan sequence
between genes. DNA is often repeated and contains useless ignspfakssgan
sequence between genes. Sensible DNA within genes can be interrupted
(ngwngiqoi) with (fehsghsdao) gibberrish. SSSSSSSSS. Sequence
may be inverted. .detrevni eb yam ecneuqeS Chemical
tags may highlight DNA to be copied. Some DNA can have
more than one meaning two messages can be created. Sequences
show where genes start and stop. |
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| Mature mRNA (Queen’s English): |
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DNA is often repeated and contains useless sequence between
genes. Sensible DNA within genes can be interrupted with gibberrish.
Sequence may be inverted. Chemical tags may highlight DNA to
be copied. Some DNA can have more than one meaning, meaning
two messages can be created. Sequences show where genes start
and stop. |
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| Translated protein (Welsh): |
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Mae ADN wedi yn ailymadrodd yn aml ac yn cynnwys
dilyniannau diwerth rhwng genynnau. Ceir rwtsh weithiau yn torri
ar draws ADN synhwyrol o fewn genynnau. Mae dilyniant yn gallu
cael ei wrthdroi. Mae tagiau cemegol yn gallu tynnu sylw at
ADN sydd i gael ei gopio. Mae ambell i ADN yn gallu golygu mwy
nag un peth, fel y gall dwy neges gael eu creu. Mae dilyniannau
yn dangos lle mae genynnau yn dechrau ac yn gorffen. |
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| Modified protein – e.g
glycolipoprotein (Welsh, French and German): |
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Mae ADN wedi yn ailymadrodd yn aml ac yn cynnwys dilyniannau
diwerth rhwng genynnau. Ceir rwtsh weithiau yn torri ar draws
ADN synhwyrol o fewn genynnau. Mae dilyniant yn gallu cael ei
wrthdroi. Mae tagiau cemegol yn gallu tynnu sylw at ADN sydd
i gael ei gopio. Mae ambell i ADN yn gallu golygu mwy nag un
peth, fel y gall dwy neges gael eu creu. Mae dilyniannau yn
dangos lle mae genynnau yn dechrau ac yn gorffen. Un N -Asn
le polysaccharide est joint ici. Eine N Terminallipidgruppe
wird hier gesetzt. |
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