So far we have discussed reassortment and
Now we discuss “allele conversion” by
change in DNA sequence that is inherited by offspring.
A mutation event
how the allele sequence changes. Two things must happen:
Mutant strain: A
population of descendents of the individual in which the original
event occurred. The “mutation” is now inherited by
the regular reassortment
and recombination mechansisms, as are other alleles.
A change in the molecular structure of DNA
Failure of editing enzymes to correct the
into new DNA
Rate of mutation:
often a given map position mutates. In practice, this is hard to
Frequency of mutation:
What percent of alleles contain a
to be “mutant,” in a given population at a given point in
is easy to measure.
Note: In nature there is no such thing as
All existing alleles are the result of the past 4 billion years of
Mutation events are
How to detect them?
large numbers of progeny. (Patience.)
For traits which confer survival advantage: Subject them to the
environment. Example: plate bacteria on agar containing an
For traits which prevent survival,
under a given
condition. Example: Replica plate bacteria colonies on agar
a nutrient which the “wild type” strain can make with its
Explain how and
why each of the above approaches reveals mutant strains. Compare
the advantages and disadvantages of each.
behavior; auxotrophy; drug resistance; conditional on environmental
mutations vs. Chromosomal mutations. Point mutations: transitions,
Silent; nonsense; missense; frameshift
Chromosome mutations: How
do they occur? Review the process of Recombination.
Think of mistakes that can happen, especially with the Holliday
and with supposedly homologous base pairing.
Point mutations: How do they occur?
Review DNA replication.
Where can "errors" creep in?
Note that many different kinds of mutation can
mRNA transcription, resulting in the same phenotype.
Successive mutations play a major role in the
and progression of malignant tumors. From the Cornell
University Medical College:
A major factor in progression
be that most tumor cells are genetically less stable than normal cells
and this instability produces variant clones. Chromosomal abnormalities
in number and structure are often seen in tumor cells. These
include: a gain or loss of chromosomes (aneuploidy);
(loss of a segment of a chromosome);
("flip-flop" of two segments of a chromosome); translocation
(rearrangement of segments between two chromosomes); and
change in the structure or expression of a gene) ranging from
change to single base-pair substitution
(point mutation). Molecular genetic mechanisms
tumor progression include: chromosomal
or mutations that "activate" cell oncogenes
loss of putative "tumor suppressor" genes.
Note: The phenotypic result of a mutation is hard
it depends on the physiology of the particular case. The
of the mutation may have no correlation with the magnitude of the
A major chromosome inversion may result in
phenotype, so long as no genes are lost.
A single base pair replacement (point
mutation) may decrease
or eliminate function of a gene, resulting in lethality. Example,
following DNA sequence into RNA:
5' A A T G G G
C T A C T T A
G C C A C T A G G C T T T A G C C 3'
3' T T A C C C G A
T G A A T
C G G T G A T C C G A A A T C G G 5'
You should find
two ways to do
Which way could be
mRNA to be
translated into a short protein? Why?
Write the protein,
genetic code in your text.
Real coding sequences
would have hundreds of base pairs.)
Why cannot the
other RNA encode
an entire protein?
following types of
"mutation" in your DNA sequence:
protein that would result
from each mutation.
Certain chemicals and environmental factors may
the rate of mutation. These are called mutagens.
The Ames test provides a rough measure of the effect of a
Base analogs which
incorporate into DNA and pair incorrectly. An example is 5-bromouracil.
Chemicals which modify
bases of DNA and cause incorrect pairing.
base pair analogs which intercalate
bases, resulting in addition
loss of a base pair. Lead to frame shift
mutations. An example is the acridine derivative
Biological mutagenesis is caused by:
High-energy electromagnetic radiation (UV
or gamma rays) cause breakage of the backbone, or
of bases, such as thymine dimers,
within genes responsible for editing lead to high frequency of
throughout the genome.
Transposable elements can insert
into a chromosome,
excise themselves out of the chromosome, or copy themselves into new
Transposition is mediated by enzymes, such as a transposase.
selection for Gain-of-function
Spread organisms on petri plate of media containing antibiotic.
those with antibiotic-resistance mutation will produce colonies.
selection for Loss-of-functionmutations:
of colonies. Replica plate or pick colonies onto non-permissive
medium. Whichever colonies fail to grow, go back to original
to obtain mutant strain.
dominant or recessive? What about loss-of-function?
||New function covers up "normal" version.
Drug resistance pump
One copy of the new
Homeotic fly gene,
makes leg instead
|Loss of function is
covered up by wild-type
allele producing enough functional protein.
Find your own disease in OMIM.
Solutions to problems