Transcript PowerPoint

Mutation and Selection
Exam - Monday
Q&A – Friday 3 PM
Higgins 300
Mutation introduces variablity
Selection increases the frequency of mutant genes
Researchers believe that bacteria contribute more to earth’s
biomass than the sum of animals and plants
“This is truly the age of bacteria:
as it was in the beginning, is now
and ever shall be”
Stephen Jay Gould
How many bacteria fit on the top
of a pin?
prokaryotes play diverse
roles in ecosystems
Bacteria are essential for life on earth
Atmospheric nitrogen can’t be used for metabolism
Nitrogen-fixing bacteria convert nitrogen to ammonia
Roots of legumes
have nodules
colonized by rhizobial
species
Cyanobacteria use water as an electron donor for
photosynthesis, producing oxygen
Cyanobacteria have chlorophyll
deposits within internal membranes
Carboxysomes are aggregates of
carbon-fixing enzymes (dark
reaction of photosynthesis)
Soils have complex bacterial populations: play important roles in
nutrient cycling, water dynamics and disease suppression
USDA – estimates one teaspoon
of soil contains between 100
million and 1 billion bacteria
(mass equivalent to 2 cows per
acre)
BIOLOGICAL WARFARE!!!
Bacteria growing
on soil fungi
Bacterial and fungal populations keep each other in
check - soil fungi are a major source of antibiotics
Bacteria have been popular models for studying
mutations because they divide quickly, doubling approx.
every 20 minutes under optimum conditions. Over a
period of two hours, one bacterium could give rise to
how many bacteria?
Mutations
Changes in the DNA sequence
Can occur anywhere in a genome
Are rare events
Can be large or small
Effects vary from none to lethality
Introduce variability into populations
Provide the raw material for evolution
An experiment in evolution
Day zero - culture is
inoculated with a genetically
homogeneous sample of plant
bacterium Pseudomonas
fluorescens
The culture is
incubated at 37
degrees for
several days
A sample is
removed and
grown on an
agar plate
several kinds of colonies
are seen after a week
(each colony has arisen
from a single cell)
Fuzzy Spreader
Wrinkly Spreader
Smooth Morph
Three morphs occupy different ecological niches when they are
used separately to start new cultures
Stable genetic changes have occurred rapidly
Different mutations are associated with each new form
Many different kinds of mutations, with different consequences
Point mutation – a single nucleotide is changed
Missense mutation – point mutation changes an amino acid
Synonymous mutation – point mutation does not change an amino acid
Nonsense – point mutation introduces a stop codon
Frameshift – nucleotides are inserted or deleted – often changes the
position of the stop codon, affecting the protein length
What causes mutations?
Chemical changes in DNA
Radiation
Errors during DNA replication
Errors in meiosis (structural changes in chromosomes)
Mutagens have characteristic signatures that can often be
identified by sequencing the mutant gene
Some mutagens (particularly radiation) can cause chromosome
rearrangements
Error in replication
Mismatched bases
Following next round of
replication, mutation is passed
on to one daughter strand
Chemical mutagens
(substances that cause mutations)
Many mutagens react
directly or indirectly
with the DNA, leading
to base changes and
errors in DNA
replication
Most chemical mutagens are also carcinogens
(substance that causes cancers)
Substances with potential mutagenic activity are all around
us (and in us)
Body converts many procarcinogens into carcinogens in
the liver
Radiation
Different kinds of radiation
have their own mutational
signatures
Most radiation exposure occurs as a routine part of life
Which kinds of mutations are inherited?
Long-term health studies of Hiroshima survivors show:
Very high rates of cancers,
especially leukemias
Somatic mutation (not germ)
cells
Children of survivors have
normal cancer rates
Germ-line mutations were not
significantly elevated
The good news: Cells have several kinds
of active DNA repair systems
World’s toughest bacterium in
Guinness Book of World Records
Withstands radiation doses that are 500
times more than that required to kill a
human
Deinococcus radiodurans
Also withstands extremes of heat, cold,
vacuum, desiccation, acid
Maintains multiple copies
of its genome and many
DNA repair enzymes
Thousands of errors are
produced and corrected in
each round of cell
replication
Different kinds of enzymes
catalyze each repair pathway
Excision repair
Enzymes detect damage
Incorrect bases are removed
Correct bases are inserted
using the undamaged strand
as the template
Several kinds of excision repair for
different kinds/extents of damage
Mismatch repair
Often due to errors in DNA
replication
Enzymes detect mismatched
bases and correct the
damage
DNA repair enzymes may play a
protective role against cancer
Selection
Mutations the confer
selective advantages will
increase in frequency in a
population
Antibiotic resistance: the coming plague?
Penicillin - the first documented antibiotic
Penicillium mold kills Staphylococcus and gram positive bacteria
Discovered accidentally by Alexander Fleming in 1929
Scaling up penicillin production to an industrial scale was
important in WWII war effort
Resistance was documented
even before penicillin was
widely available for clinical use!
Pharmaceutical companies have
modified penicillin structure to
generate additional antibiotics
Produced synthethically today
Fleming shared Nobel Prize with Florey and Chain, 1945
The target of penicillin is an
enzyme required to build the
peptidoglycan layer of the cell
wall
The microbes strike back
Tracks 20-24