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Genetic
Code -
Information
flow
in
biological
systems
occurs
from
nucleic
acids
to
proteins
and'
this
conclusion
has
come
largely
from
the
work
of
George
Beadle
and
Edward
Tatum.
Their
early
experiments
with
Neurospora
led
to
the
discovery
that
alteration
in
genetic
structure
by
mutation
leads
to
changes
in
the
phenotypic
characteristics
and
suggested
that
the
primary
action
of
each
gene
is
to
control
the
formation
of
a
protein.
On
the
basis
of
these
experiments
Beadle
and
Tatum
proposed
the
famous "one
gene-one
enzyme" hypothesis.
This
has
been
now
modified
to "one
gene-one
polypeptide" hypothesis,
after
it
became
known
that
proteins
or
enzymes
are
generally
aggregates
of
more
than
one
kind
of
polypeptides.
This
hypothesis
is
correct
to
a
very
great
extent
and
applies
to
all
organisms.
However,
it
is
now
known
that
certain
genes
also
direct
the
formation
of
ribosomal
and
t-RNA
molecules
and
not
the
formation
of
proteins.
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It
is
also
known
that
some
regions
of
DNA
may
be
transcribed
but
not
used
to
synthesise
peptides
subsequently.
Other
than
these
exceptions,
the
synthesis
of
a
protein
is
through
RNA
molecules
and
this
is
what
is
now
known
as
the
central
dogma
(DNA
-->RNA
-->
Protein).
Information
regarding
how
DNA
directs
the
synthesis
of
a
protein
has
come
from
different
investigators.
Sanger
and
his
colleagues
in
1953,
found
that
the
sequence
of
amino
acids
in
the
insulin
molecule
from
a
variety
of
animals
such
as
cattle,
pig,
sheep,
and
horse
except
for
some
minor
amino
acid
replacements,
was
very
similar.
These
minor
changes
were
presumed
to
have
arisen
during
the
course
of
evolution
by
mutation
without
affecting
the
function
of
this
molecule.
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Comprehensive
studies
on
the
haemoglobin
chains
(Haemoglobin
contains
two
identical α-chains
and
two β-chains)
from
normal
and
sickle
cell
anemia
by
Ingram
and
his
colleagues
in
1956
showed
that
the
haemoglobin
from
patients
with
sickle
cell
anemia
varied
slightly
from
the
normal
haemoglobin
and
that
the
difference
was
due
to
a
change
in
one
amino
acid
in
the β-chain.
This difference in function was concluded to be due to an alteration within a single gene.
More direct evidence on the effect of mutation on the sequence of amino acids in a peptide came from the early work on tobacco mosaic virus. This virus consists of one type of protein and RNA. Wittman and others treated the virus with mutagens and isolated various mutants that had variations in the amino acid chain of the coat protein. Since it was by then well known that mutagens affect only nucleic acids, it was concluded that a mutation in the nucleic acid (RNA) had caused a change in the amino acid sequence of the peptide.
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Strong
evidence
to
support
this
line
of
thinking
came
from
the
laboratory
of
Charles
Yanofsky.
He
and
his
coIleagues
were
studying
the
gene
trp
5
in
E.
coli
that
controls
the
formation
of
the
enzyme
tryptophan
synthetase.
Their
work
showed
that
the
position
in
which
a
number
of
different
mutations
occur
along
a
gene
are
in
the
same order
as
the
positions
in
which
the
amino
acid
substitutions
they
produce
along
the
peptide
chain.
This
suggested
that
the
gene
and
peptide
are
colinear.
Support
to
this
also
came
from
Seymour
Benzer
who
showed
that
in
the
bacteriophage
T2
a
mutation
is
a
consequence
of
a
change
in
a
segment
of
the
DNA.
All
this
meant
that
a
change
in
nucleotide
sequence
of
DNA
results
in
a
change
in
the
amino
acid
sequence
in
a
corresponding
position
along
a
peptide
chain.
Thus,
it
appeared
that
a
group
of
nucleotides
must
be
responsible
for
the
insertion
of
one
particular
amino
acid
into
the
peptide.
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As
mentioned
earlier,
DNA
is
composed
of
two
strands
of
poly
nucleotides.
Each
polynucleotide
contains
only
four
bases
while
the
peptides
contain
20
amino
acids.
Logically,
it
would
therefore
be
impossible
for
either
one
or
two
pairs
of
nucleotides
to
direct
the
incorporation
of
the
20
amino
acids.
This
is
because
if
one
nucleotide
directed
the
incorporation
of
one
amino
acid,
then
we
would
have
seen
peptides
with
only
four
amino
acids.
On
the
other
hand,
if
two
nucleotides
directed
the
incorporation
of
one
amino
acid,
only
16
amino
acids
should
have
been
found
(42=
16
pairs).
This
led
to
the
suggestion
that
perhaps
a
triplet
of
nucleotides
direct
the
20
amino
acids
into
the
peptide
chains
because
there
can
be
64
combinations
(43=64),
adequate
enough
to
code
for
the
20
amino
acids
generally
found
in
the
proteins.
The
simplest
coding
ratio
would
therefore
be
a
triplet
nucleotides
(three
nucleoli
des)
for
one
amino
acid.
Evidence
in
support
of
this
type
of
thinking
accumulated
from
a
variety
of
experiments
carried
out
by
Crick,
Benzer,
Nirenberg,
Khorana
and
others
and
it
was
soon
concluded
that
a
set
of
three
nucleotides
direct
the
insertion
of
one
amino
acid
into
the
peptide.
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As
early
as
in
the
fifties,
it
was
known
that
most
proteins
are
synthesized
in
the
cytoplasm
while
DNA
exists
in
the
nucleus.
Because
proteins
are
synthesised
on
the
ribosomes
rather
than
on
the
genes,
it
was
presumed
that
some
kind
of
intermediate
of
the
gene
directs
the
assembly
of
the
amino
acids
into
proteins.
Since
nearly
two thirds
the
weight
of
ribosomes
was
RNA
and
proteins
were
established
not
to
be
the
genetic
material,
it
was
suggested
that
perhaps,
RNA
found.
in
the
ribosomes
carries
an
imprint
of
the
gene.
If
that
were
so,
the
sequence
of
this
RNA
should
have
a
direct,
relationship
to
the
sequence
of
DNA
from
where
it
was
copied.
This
theory
was
vigorously
tested
using
cell
free
bacterial
systems.
However,
it
was
found
that
the
RNA
found
in
the
ribosomes
had
no
ability
to
direct
peptide
synthesis.
In
1957,
E.Volkin
and
L.
Astrachan
reported
that
in
E.
coli
the
RNA
formed
soon
after
infection
with
either
T2
or
T7
bacteriophages,
had
a
sequence
complimentary
to
the
DNA
sequence
of
the
bacteriophage.
The
RNA
synthesized
after
infection
was
isolated
and
was
found
to
hybridize
with
only
one
DNA
strand
of
the
bacteriophage.
It
was
concluded
that
an
intermediary
type
of
RNA
called
the
m-RNA
(messenger
RNA)
is
formed
on
only
one
strand
of
the
DNA.
The
m-RNA
after
synthesis
associates
with
the
ribosomes
and
other
factors
and
allows
peptide
synthesis.
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