The Genetic Code
n
In principle: The DNA genotype produces the phenotype indirectly
A DNA gene contains the information
necessary for the production of proteins,
which is expressed biochemically through an
intermediate molecule, RNA,
The Genetic Code is an RNA code that specifies amino acids that make up proteins
was "cracked" before the biochemistry of translation was understood:
we can talk about
the Code before (or without)
describing RNA translation Alternative alleles of genes arise by mutations
which alter the DNA sequence of genes
which may cause amino acid substitutions in proteins
which may affect the function of those proteins
which appear in the population as Single Nucleotide Polymorphisms (SNPs)
Most genes are highly polymorphic
The "Universal" Genetic Code is
...
a messenger RNA (mRNA) code
DNA carries genetic information,
but is not the 'Genetic Code' in the
biochemical sense
in 64 codons : 61 for amino acids + 3 'stops' [Table]
mRNA codons are read 5'
3'
Triplets are equivalent
three-letter motifs in DNA
20 amino acids:
note 1- & 3-letter abbreviations
Degenerate: most amino acids encoded by more
than one codon
first
two
positions
are
critical:
third position can "wobble"
if third can be either puRine (R), or either pYrimidine
(Y)
two-fold degeneracy
if third can be any base
four-fold degeneracy
Leucine (leu) has six-fold degeneracy with
six codons in unusual arrangement:
| Amino
Acid |
# codons |
| Trp,
Met |
1 @ |
| Ser, Arg, Leu |
6 @ |
| Ile |
3 @ |
| Tyr, Cys,
His, Gln, Asn, Lys, Asp, Glu
|
2 @ |
| Ser, Pro,
Arg, Thr, Val, Ala, Gly |
4 @ |
Unambiguous: any one triplet codes for only
one amino acid
but not vice versa, because of wobble
'Always' begins with an 'start' or 'initiator'
codon:
AUG
'Always' ends with a 'stop' or 'terminator' codon: UAG, UAA, or UGA
Universal (with some important exceptions)
Five Kingdoms
(animals, plants, algae, fungi, & monera)
use
same code for nuclear DNA
(nucDNA)
Organelles (chloroplasts
& mitochondria) have separate genomes:
cpDNA & mitochondrial DNA codes
evolutionarily modified
e.g., UGA codes for trp
(W) in vertebrate mtDNA
code
AUN may
act as Start Codons in invertebrate
mtDNA code
Stop codons may be
formed by addition of "A"s to transcript
Lab exercises use mtDNA data, so the mtDNA codes are
important
>
30 alternative codes in various evolutionary lineages
Alteration & Variation in the
Genetic Code: Mutations & SNPs
Mutations
- interchanges of
one base type for another
transitions -
alternative pyrimidines [
C
T ]
or purines [ AG ]
transversions - purines pyrimidines [C /
T A
/ G]
Recognized in
individuals & populations as SNPs ("snips": single
nucleotide polymorphisms)
SNPs, Mutations, & Mutants:
a note on terminology & some lessons from
history
Alternative nucleotide sequences
of a gene
correspond to alternative alleles
or: a single gene occurs
in
variant forms (alleles)
Single-base mutations
Consequences of exon
SNPs depend on position in triplet
3rd position
typically a silent mutation -
if 2- or 4-fold degenerate "wobble", no change to amino
acid
sometimes a mis-sense
mutation -
results in different amino acids
2nd position - always a mis-sense mutation
1st position - almost always a mis-sense
replacement
6-fold degenerate Leu codons the exception
stop codon mutations may occur at any position: coding 
non-coding
triplet
non-sense (termination) mutations terminate polypeptides
prematurely
[Distinguish non-sense
from "nonsense" mutations]
: Identify all
codons one
step away from a termination codon
mutations in non-coding DNA have variable
effects
Ex.: mutations in promoter
regions
mutations at intron / exon
splice junctions
Proteins mutate!
Consequences depend on position of substitution in polypeptide
none: substitution not in active site or binding site
minor: substitution of same type (synonymous substitution)
Allozymes are enzymes arising from allelic variation of enzyme genes
major: substitution affects structure / function (nonsynonymous substitution)
Ex.: Glu
Val in beta-globin
produces Sickle-cell
hemoglobin (HbS): What is the DNA mutation involved?
Insertion / Deletion ("indel")
mutations
gain or loss of one or two nucleotides alters the reading
frame
frameshift mutations
(examples)
single & double nucleotide
indel downstream amino acids change
non-sense mutation eventually (quickly) produced
triplet indel - insertion /
deletion of single amino acid
typically milder consequences
multiple triplet insertions produce major effects
Ex.: CGG repeats in "Fragile X" Syndrome
length mutations - very large
indels (102~6 bps)
Genes
are highly
polymorphic (multiple alleles) due to SNP
variation
has 14 exons, encodes 2.4kb mRNA for 452 amino acid protein
Among 68 alleles that affect enzymatic activity of PAH [GenBank List]
68% mis-sense SNPs (many produce Phenylketonuria (PKU))
13% non-sense SNPs (premature termination)
9% indel SNPs (single base
1~5 triplets whole
exon)10% splice-site SNPs (including most common variant allele)
Most allelic variants of the PAH locus are 3rd position silent:
no affect on PAH expression
& therefore undetected
Homework #10:
(1) "What is a Gene?" Write a one-paragraph essay that that distinguishes Gene, Allele, and Locus
(2) Critique the following statements:
"PAH is the gene for Phenylketonuria (PKU)."
"PKU is a genetic disease caused by absence of the PAH gene."
Text material ©2025 by Steven M. Carr
