Reading the Messages in Genes
Biotechnology Industry Organization (BIO). "Biotechnology in
Perspective." Washington, DC: Biotechnology Industry Organization,
1990.
The implications of the double-stranded structure of DNA are
far-reaching, and were immediately obvious to Watson and Crick
when they presented their model in 1953. As they described it, each
DNA strand is precisely complementary to the nucleotide sequence of
its partner strand, and consequently both contain the same genetic
information. If the two strands are designated A and B, then A can
serve as a mold or template for B, and vice versa. Genetic
information is copied by a process in which strands A and B separate
and unwind, enabling each separated strand to become a template for a
new complementary partner strand. The result is that in both
offspring of a divided cell, each DNA molecule has one original strand
and one newly synthesized strand. This mechanism of semi-conservative
replication ensures precise copying of the nucleotide base sequences
in DNA.
A typical animal cell contains a meter of DNA. Each nucleotide,
A,C,T, or G can be regarded as a letter in a four-letter alphabet used
to write messages in the form of a kind of linear (biological) coded
tape. So the number of possible sequences in an animal cell would
fill several thousand books with continuous text. Much less DNA is
found in the virus X174, which infects bacterial cells and whose
complete DNA sequence can be written on a single page. The principles
of gene replication are readily intelligible, but the biochemical
machinery by which this copying mechanism takes place is complex and
involves many enzymes.
In the early 1960s, the genetic code was cracked. An adjacent group
of three nucleotides (triplets) was shown to code for an amino acid.
With 20 amino acids and 64 possible triplets, most amino acids are
specified by several triplet 'codons.' The genetic code is universal
and is the same in organisms as diverse as viruses, bacteria, plants,
animals, and man. It is this universality of the genetic code that
permits a bacterial cell into which a section of mammalian DNA has
been transferred to make perfect sense of the incorporated message.
Without this universality, much of modern biotechnology would not
exist.
Errors Lead to Mutations
Unraveling the genetic code demonstrates the need for precision in DNA
replication. Errors in a particular codon could lead to the wrong
amino acid being specified at some point in a protein molecule. This
could result in a shape change sufficiently dramatic to change the
function of that protein. Errors in replication, and those induced by
external agents such as prolonged exposure to UV, X-rays, and
radioisotopes, are known as mutations.
Organization of DNA in Cells
The DNA in a bacterial cell forms a single loop-like structure,
whereas in animal and plant cells separate molecules of DNA
(chromosomes) can be identified. These are complex structures, each
containing many genes and packaged with closely associated DNA binding
proteins (the histones). Associated proteins are important in
regulating gene activity in cells. Many of the recent developments in
our knowledge of DNA sequences encoding for specific proteins have
stemmed from the elegant sequencing procedures devised by Fred Sanger
and his colleagues in Cambridge, England.
Proofreading the Code
Decoding the base sequence of DNA to make proteins is a complex
process with built-in molecular checks and safeguards to ensure that
the instructions are correctly read. The cell is also actively at
work to preserve the accuracy of the DNA code and eliminate errors.
It was the physicist Erwin Schrodinger who pointed out in 1945 that
the observed complexity of living organisms requires that individual
genes consist of very few atoms so that the genome can be accommodated
in a cell.
Because of its size, a gene would be expected to undergo significant
changes due to random spontaneous reactions arising from thermally
induced collisions of molecules. The dilemma is real. It may come as
a surprise to learn that there are several thousand errors induced in
your DNA each day! No need to panic, however - some 20 different
enzymes are at work continuously proofreading and eliminating these
errors. The repair mechanisms all depend on the existence of two
copies of the genetic information - one on each strand of the DNA.
Thus, mutations are relatively rare, although their presence at low
frequency contributes to their variation in populations of organisms,
which is essential to evolution.
Copying and Translating Genes
Protein synthesis using the blueprint contained in the DNA sequence of
nucleotides in the form of the genetic code is achieved by first
copying particular regions of DNA into a chemically and functionally
different kind of polymer known as 'messenger' ribonucleic acid (RNA).
The coding section of DNA that is copied contains the gene for a
specific protein, and it can be copied many times. Like DNA, RNA is a
linear sequence of nucleotides, but there are two minor chemical
differences. First, the sugar-phosphate backbone of RNA contains
ribose instead of a deoxyribose sugar. Second, the base thymine (T)
is replaced by the closely related base uracil (U). Additionally, no
complementary strand is present.
Transcription of the Code
RNA retains faithfully all the information of the original DNA
sequence, and the process of RNA synthesis is known as DNA
transcription. It shares some common features with DNA replication
itself, in that the first step is the opening up of the DNA double
strand in the region to be copied. Then one of the two strands of DNA
acts as a template for the synthesis of RNA.
Here the similarities end. There are several essential differences
between DNA and RNA synthesis. For example, the RNA strand does not
stay attached to the DNA. As soon as the copy is completed, the DNA
double-stranded helix reforms and the RNA is released as a single
strand. RNA molecules are also much shorter than DNA itself,
representing only a minor fraction of the genome. The production of
RNA from a single gene can be carefully controlled by the cell - this
is achieved by gene regulatory proteins, and this regulation of gene
copying is important in controlling the differentiation and
development of cells in all complex multicellular organisms.
A Messenger Molecule
Many thousands of RNA copies can be run off from the same DNA segment
during each cell generation. In the cells of higher organisms, many
of these RNA molecules undergo major changes before leaving the
nucleus to act as messenger molecules (mRNA) that direct the synthesis
of proteins. Translation of the mRNA molecules takes place in the
cell cytoplasm at specific protein synthesizing stations called
ribosomes. These particles are barely discernible in the electron
microscope, and their fine structure is slowly being unraveled.
Composed of RNA and proteins, ribosomes allow the message to be
decoded and enable assembly of the building blocks of proteins (amino
acids) in their correct sequences.
Translation of the Code - Protein Synthesis
Three nucleotides (a codon) encode a single amino acid and, though
there are specialized start and stop sequences, the bulk of an mRNA
molecule is made up of a linear sequence of codons each specifying an
amino acid. The mRNA tape is threaded through the ribosome like punch
tape and the appropriate amino acids are added to the growing protein
molecule.
However, the mRNA do not directly recognize the amino acids that they
specify, in the way that an enzyme recognizes a substrate. The
process of translation employs adaptor molecules that recognize both
an amino acid and a group of nucleotide bases. These adaptor
molecules are a family of RNA molecules known as transfer RNAs
(tRNAs), each of which is between 70 and 90 nucleotides in length and
with a looped structure produced by folding of the tRNA single strand.
This characteristic shape is essential to its functional role as an
adaptor.
Of special importance are two sets of three unpaired nucleotide
residues in the tRNA molecule. One of these triplets forms the
anticodon region which can base-pair to a complementary triplet in
mRNA. A triplet at the free end of the tRNA molecule is attached to a
particular amino acid. With a separate tRNA for each amino acid, only
the tRNA carrying the correct amino acid can bind to the section of
mRNA exposed for translation on the ribosome. By threading the mRNA
codons in sequence through the ribosome, tRNA molecules bind
successively and add their amino acid cargoes to the growing protein
until it is complete. When the ribosome reaches the end of its
message, both message and protein are released.
Go to Graphics Gallery: The Structure of DNA,
DNA Replicating Itself,
RNA and DNA,
Protein Synthesis
Go to next story: The Search for DNA - The Birth of Molecular Biology
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