Download Salmonella typhimurium

The main properties of DNA
• The genetic material must be able to:
–
–
–
–
Store information
Replicate (when cells divide)
Express information (as proteins)
Mutate at a low frequency (less than 1 in a
million)
• DNA is a molecule that is very well suited
to doing all 4 of these
Mutation
• Can occur in any cell at any time, cause may be:
– Internal (e.g. mistakes during replication of DNA)
– External (e.g. radiation, chemicals)
• Most mutations have no effect (neutral)
• A few mutations are harmful
• A very few mutations are beneficial
• Only harmful and beneficial mutations are acted on by
natural selection
• Mutations may be non-coding (not in part of gene that
codes for protein - have no effect, or affect gene
expression) or coding…….
Effects of coding mutations
•
•
•
•
•
Synonymous: the cat ate the rat
Missense:
the fat ate the rat
Nonsense:
the cat ate the
Frameshift: the cax tat eth era t
Synonymous has no effect on protein,
nonsense makes a smaller protein,
missense/frameshift make incorrect protein
Conditional mutations
• The effects of many coding
mutations depend on
environmental factors
• Siamese cats have mutation in
enzyme for black pigment
production, that stops it
working at normal body
temperature
• Cooler parts of cat are dark
because enzyme OK at lower
temperature
Mutation during DNA replication
• Replication of DNA is not perfectly accurate, but
there are several ways to correct the mistakes
ACGTACGTAACGTG...
TGCATGCATTGAACGGT
DNA polymerase makes about 1 mistake per 105 bp.
DNA polymerase has a “proof-reading” activity to correct its
own mistakes (99%).
After DNA replication there is a “mismatch repair” system to
correct remaining mistakes (99.9%).
This leaves an overall error rate of about 1 base in 1010.
Mutation due to environmental factors
• Mutations may be caused by chemicals or
radiation
• Chemicals (“mutagens”) may disrupt
hydrogen bonds between bases, by
modifying them or getting between them
• Radiation (including ultra-violet and
radioactive emissions) can damage structure
of bases
• These agents may be natural or man-made
DNA excision repair
• Another system to repair mutated or
damaged DNA
a
g
Mutated DNA
a
g
One strand is nicked
a
DNA removed between nicks
a
t
Correct DNA is synthesised
Application - mutagen testing
• Mutation in somatic (body) cells during the lifetime of an
animal can cause cancer
• It is vital to know if chemicals to which we are exposed are
mutagenic
• Bacteria can be used to test this: the Ames Test
• Reverse mutation is where the mutant form of an organism
mutates again, to go back to the original wild-type state
• The Ames Test uses a mutant strain of bacterium
Salmonella typhimurium that cannot make the amino-acid
histidine…..
The Ames Test
Culture of
His- bacteria
Petri dishes containing chemical to test,
liver extract, no histidine
The more mutagenic the chemical,
the more His+ colonies are produced
Amount chemical
Phenotype, Genotype, Alleles
• The phenotype of an organism is its observable
properties
• The genotype is the set of alleles it has for all of
its genes (5,000 in bacteria; 40,000 in humans)
• The relationship between genotype and phenotype
is what genetics is all about
• New alleles are created by mutation and their
effect the phenotype may be dominant or recessive
Significance of genetic variation
• Some alleles directly cause specific traits, such as
(in humans) rare genetic diseases e.g. Cystic
fibrosis, sickle-cell anaemia; (in bacteria) ability to
grow on certain sugars
• Many alleles contribute to many traits of an
organism such as size, shape, intelligence,
behaviour, and risk of getting diseases e.g. (in
humans) cancer, heart disease, asthma
• Genetic variation is what evolution acts on.
Without it there would be no different species.
Multiple genes and quantitative traits
• Many traits like height, IQ show
a bell-shaped (normal)
distribution in population
• These are influenced by several
genes, so the overall effect
depends on the random selection
of alleles in an individual
• e.g. for height genes, you are
more likely to have a mixture of
tall and short alleles than all tall
or all short
height