Lec 12: THE CHARACTERISTICS OF THE

GENETIC CODE

WHY TRIPLET CODE?

● Before the genetic code was cracked,
it was a mystery as to how 4
nucleotides could code for 20 amino
acids
● One nucleotide (41 = 4) and two
nucleotides (42 = 16) would not suffice
● Three letters (43 = 64) to a codon was
the most likely option
● Experimental research on bacteria
proved it CORRECT!!!! DEGENERACY OF THE CODE
● The genetic code is degenerate (e.g.
THE CODON each amino acid can be coded for by
more than one codon although each
Marshall Nirenberg & J. Heinrich codon only codes for one amino acid)
Matthaei in 1961 ● Of 20 a.a., 18 are encoded by 2 or
● Their experiment was a major step to more codons
break the genetic code using synthetic ● This degeneracy was explained by
poly-U RNA in an E. coli translational Crick (1961) in his Wobble Hypothesis
machinery to get polyphe (F) ● It simply states that the 1st two
positions (on mRNA & tRNA) pair
Har Gobind Khorana precisely, but pairing at the third
● proved that the nucleotide code is position may be ‘wobbly’
always transmitted in the cell in
groups of 3 called codons & that some
of them prompt the cell to start or stop
protein synthesis
● It is comma free (e.g. mRNA is read
three bases at a time without skipping
any bases)
● It is non-overlapping or
non-ambiguous (e.g., each nucleotide
is part of only one codon & is read
only once during translation)
UNIVERSALITY OF THE CODE LACTOSE OPERON (Lac Operon)
● The genetic code is universal, i.e. ● INDUCIBLE operon
most codons have the same amino ● Presence of lac changes the
acid meaning in nearly all living conformation of the repressor (inactive
organisms form) by allolactose. Repressor is
● Exceptions in mitochondria where unable to bind to the operator
UGA = UGG (for trp) & AUA = AUG ● Allolactose acts as an INDUCER that
(for met) TURNS the gene ON

START AND STOP CODONS

● It has START signal (AUG)& defines
the open reading frame
● STOP signals (UAA, UAG & UGA)
with no corresponding tRNA

PROKARYOTES REGULATION OF GENE

ACTION

GENE REGULATION
● Individual genes are not expressed all
the time (differential gene expression)
& is accomplished thru gene
regulation
● Genes can either be inducible (not
expressed all the time but can be
induced) or constitutive (expressed all
the time) TRYPTOPHAN OPERON (Trp Operon)
● Prokaryotes have a single piece of ● REPRESSIBLE operon
circular, double-stranded DNA where ● Presence of trp turns repressor into
an operon can be found active form such that the gene is
TURNED OFF
OPERON ● Repressible operons are usually
● Term coined by Francois Jacob & TURNED ON until metabolite
Jacques Monod (Nobel Laureates, activates the REPRESSOR
1965)
● Consists of genes grouped together; LAC & TRP OPERONS ARE NEGATIVE
transcribed into single mRNA CONTROL OF A
containing coding sequences for more PATHWAY!!!!
than 1 gene (polycistronic). Grouped An example of POSITIVE CONTROL is the
together with one promoter ARABINOSE OPERON (Ara operon) that
● Can be inducible or repressible converts L-arabinose to xylulose-5-P that
● Allows for coordinated control of provides energy to the cell
genes required for metabolism
 ● Ara C proteins have 2 conformations ● Gene expression can be turned on by
with P1 acts as repressor in O signals from outside a cell.
● With the presence of ara, P1 removes ● External signals (neurotransmitters or
from O with P2 binds to the initiator to hormones) interact with transcription
express the genes factors to activate the transcription of
the gene.

DEVELOPMENTAL GENETICS
● The field that studies the relationships
between gene regulation & cell
differentiation during development
EUKARYOTES REGULATION OF GENE ● 2 important stages in the formation of
ACTION different cell types:

Differential gene expression

Gene Regulation
● Eukaryotes tend to have solitary
genes rather than operon.
Differential gene expression &
● Based on Davidson-Britten Model
development
(1979), sensors, each adjacent to an
● The fate of a cell describes what it will
integrator gene, recognize various
become in the course of normal
molecular signaling agents.
development
● Once the sensor is activated, the
● The development potential or potency
integrator gene is transcribed to yield
of a cell describes the range of
activator RNA.
different cell types it can become
● Activator RNA is recognized by one or
● Determination of different cell types
more receptors where structural genes
(cell fate) involves progressive
are transcribed.
restriction in their developmental
potentials. When a cell ‘chooses’ a
particular fate it is said to be
determined
● Differentiation follows determination
as the cell elaborates a cell-specific
developmental program.
Differentiation results in the clear-cut
identities of cell like muscle cells,
nerve cells & skin cells (phenoclones)
Mechanisms of determination (loosely coiled) is more easily
Determination results from the asymmetric transcribed to mRNA
segregation of cellular determinants (usually ● DNA Methylation – methyl groups
proteins or mRNAs). During cell division one maybe added to C residues to
daughter cell receives most or all of the reinforce that the genes are
localized molecules; while the other receives inactivated
less or none!!! This results in 2 different
daughter cells which then take on different cell Chromatin structure
fates based on differences in gene
expression.

Images of C. elegans fertilized embryo with

fluorescentlylabelled P granules

DNA methylation

Selective gene expression

● Pre-transcriptional control 2. Transcriptional control
● Transcriptional control ● Different RNAs are synthesized at
● Translational control different rates during successive
● Post-translational modifications stages of development
● Different mRNAs can be made from
1. Pre-transcriptional control the same primary transcript by
● Gene amplification (differential alternate splicing, i.e. different exons
replication of certain genes) – certain used for mRNA would end up coding
portions of genomes are replicated in for different protein
excess to synthesize vast quantities of ● Selective degradation of pre-mRNA
rRNA in a relatively short period of also means a gene regulation (~75%
time (amphibian oocytes) are degraded in the nucleus)
● Chromatin structure – heterochromatin ● Different regions or sequences of
(DNA tightly coiled) is generally not DNA: different transcripts for genes
transcribed whereas euchromatin with 2 or more TATA boxes (promoter
region); upstream promoter elements
 very close to the promoter will different amounts of proteins are
increase transcription when specific produced before and after fertilization
transcription factors bind; enhancer ● The longer the half-life of the mRNA,
region much farther from the promoter the longer is the time it can be used
will increase transcription with during translation
activator protein & prevent it for ● The longer the poly A tail, the longer
silencer region with the repressors. the mRNA can exist

4. Post-translational control
● Most proteins are modified after
translation (epigenetic modification)
with the addition of sugars or
phosphate groups, or the removal of
sequences after they crossed a
membrane
● Phosphorylation (modification by
putting on phosphate groups) and
combination of phosphate groups
generate isozyme forms (eg. glycogen
phosphorylase)
● Bovine proinsulin must be cleaved into
2 polypeptide chains & ~30 a.a. must
be removed to form insulin

● The study of mechanisms that change

the gene expression by modifying the
3. Translational control DNA without altering its base
● Different rate of protein synthesis sequence.
according to developmental stage e.g. ● Development is epigenetic (Wolf Reik,
Cambridge University).
 ● The patterns of gene expression are
governed by epigenome (‘epi’ means
above), a genome-wide distribution of
epigenetic marks which sit on top of
the genome that tell which genes to
switch on or off.

Mechanisms
1. DNA Methylation
● Methylation accounts for the very
specific patterns of silencing and
activating genes in every cell.
● Active genes are under-methylated
(low in methyl groups)

Twin lab mice are genetically identical but

phenotypically different: one has brown coat, 3. Non-coding RNA
the other yellow (called agouti). Both have ● Fire and Mello (Nobel winners, 2006)
agouti gene, but the difference lies on discovered RNA interference (RNAi).
methylation: In healthy mouse, methyl group ● Double stranded noncoding RNAs
binds to agouti gene silencing it during (dsRNA), seen in eukaryotic cells as
development source of viral infection, can be used
to silence the expression of target
genes.
● RNAi involves short (21 nucleotides),
single stranded RNAs called
microRNAs (miRNA) that inhibit
translation and small interferring RNAs
(siRNA) that cause RNA degradation.

2. Modifications of histones
● Chromatin structure can change when
histone proteins are chemically
modified;
● Histone methylation tightens up DNA
thus restricting access to genes while
acetylation unravels the DNA making
genes more available for activation.