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Cloning
• A clone is an exact genetic copy of
an individual
• Many organisms have clonal
reproduction: fission (bacteria,
protozoa), budding (some plants,
invertebrates), parthenogenesis
(some fish, insects, lizards)
• Clonal reproduction of plants, using
cuttings or other culturing
techniques, mastered by humans for
millennia (e.g. bananas)
Asexual Organisms
A few species, like this
gecko, are parthenogenic.
This means that all
individuals are female,
and their offspring are
exact genetic copies of
themselves, or clones.
Asexual Organisms
Most asexual species have close relatives that are
sexual. The whiptail lizard is a parthenogenic
species that formed as a hybrid of two other species.
It tricks males of the other species to mate with it,
because it needs sperm to activate its eggs
Cloning
•
Vertebrate cloning difficult – especially
mammals & birds
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•
Dolly was 1of 276 attempts
Current technology:
(1) Harvest the nucleus of a cell from an adult
(2) Inject it into an egg cell that has had its nucleus
removed
(3) Make sure that cells begin to divide normally (an
embryo begins to form) – This is the hard step
(4) Place the developing embryo in a foster mother
Cloning
•
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Cloning (potentially) permits the rapid, economical
reproduction of individuals with desirable traits
With serial cloning, genetic lines can be preserved
(almost) exactly
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Serial cloning may destabilize chromosomes
Mutations will accumulate – a cost of clonal reproduction
Even though the nucleus of the egg is removed, some of
the egg-donors genes remain, in the mitochondria – thus
the first generation is not a perfect clone
Long term risk in terms of lost genetic diversity
–
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More vulnerable to disease epidemics
Less variation to adapt to environmental change
Gene ‘Therapies’
• Introduce substances that halt the activity of
certain genes (AZT)
• Introduce substances that (over) promote
activity of certain genes (gamma globin)
• Introduce new, functional genes true Gene
Therapy
– Experimental, currently tested primarily on critically ill
patients
Gene Therapy
• Vehicle or Vector
– e.g. weakened virus
• Recipient cells
– cultured cells or in vivo somatic cells e.g bone
marrow
• The introduced sequence
– Marker (so you know it worked)
– Promoter (to cause transcription)
– The Gene
Marker
The Problems
•
•
•
•
Must immuno-suppress the patient
Efficiency of transfer often low
Duration of expression often short
Unknown risks… permanent unwanted
changes (mutations) to somatic (or germ
cells), viral infections, cancer or other
diseases associated with breakdown in genetic
regulation?
Genetically Modified (Transgenic) Crops
• 50% of soybeans, 25% of corn grown in the US are
transgenic (have a gene from another species added via
biotech)
• Main transgenic traits: herbicide tolerance, Bt toxins to
kill insect pests, virus resistance
• Future transgenic traits: vitamins, vaccines (inactivated
viruses)
• Potential to reduce uses of agrochemicals, increase food
production, improve quality of plant products (including
novel ones)
Genetically Modified (Transgenic) Crops
• Using specialized enzymes, chop up gene sequences,
select and connect desirable sequences to form a
‘cassette’
– Sequence must include a marker, promoter, transgene
– Flanked by ‘sticky ends’
• Infect a bacteria (E. coli) to produce quantities of
cassettes via bacterial clonal reproduction
• Purify sequences, inject sequences into cells
– Gene gun
– Infective bacteria
• Select plant cells with the marker
• Propagate selected plants clonally
• Produce new plants clonally or through sexual crosses
Marker
Non-transgenic
Transgenic
Problems with Transgenic Crops
• Doesn’t work very well - yet
• Risk of traits spreading to weeds, producing ‘super
weeds’, or pests developing resistance to transgenic
defenses
• Risk to non-target organisms
• No unusual health risks (?), requires strict testing
• Reduced genetic diversity puts crops at (long term) risk
• Agricultural resources become monopolized by a small
number of gigantic agrobusinesses
Transgenic Animals
Potentially quite useful
• Animal models of human diseases by introducing
human genes
• Targeted production of pharmaceutical proteins
(human enzymes, hormones, growth factors)
• Modification of animal anatomy & physiology
Transgenic Animals
• Create ‘cassette’: enhancer + promoter + gene plus sticky
ends
– Enhancer often designed to restrict activation of the gene to a
targeted tissue (e.g liver) only
• Infect a bacteria (E. coli) to amplify the cassettes via
bacterial clonal reproduction
• Collect and purify the cassettes, test for activation in
eukaryotic cells
• Inject cassettes into a newly fertilized egg cells
• Transfer embryos into a surrogate mother
• Analyze babies, breed or reproduce clones of those that
express the transgene and have the fewest other problems
Problems with Transgenic Animals
• Doesn’t work very well – yet
– Cassettes integrate randomly into genome, sometimes
knocking out genes
– Sometimes multiple copies integrate
– Integration not always stable
• Same worries as transgenic crops
• Animal welfare