Transcript Powerpoint
Semester projects!
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Miraculin paper based!
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Find a partner with same TA (needn’t be same section)
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You will
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Be supplied with suspicious red tablets!
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Be expected to support/refute a claim from the paper
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Read & reference >= 1 reference from the Miraculin paper
as well as the paper itself
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Be awarded 3 point bonus for improving on the Dr.
Pepper!!!
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Midterm musings
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How are bases & amino acids suited to their tasks?
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How does hemoglobin function as a machine?
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pH triggers
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DPG--how & why; fetal changes
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Cooperativity
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Periodic table: clues & progress
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siRNA: send a thief to catch a thief
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tamiflu: tracing lineages through mutations
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Blue eyes & milk drinking: single vs. multiple origins (hemo?)
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Does milk make you
gassy?
Why/why not?
What’s normal? What’s the discover?
*According to dictionary.com: the necessary changes have been made
Key concept:
DNA is historical record
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You got your genes at the Parent’s store
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So did they
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ad infinitum
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Conclude: Your genes are not your own. They are a copy of
a copy of a copy of a copy…
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They contain a record of who (what) you were
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What’s milk got?
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‘milk sugar’ = lactose =
http://commons.wikimedia.org/wiki/File:Alpha-lactose-from-xtal-3D-balls.png
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Imagine a normal mammal...
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not some bizarro cross-species-suckling human!
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...where do you get milk?
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...when do you get milk?
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when do you no longer get milk?
Is it pointful to build milk-processing bioMachines (enzymes)
for your entire life
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If you don’t digest it...
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gut bacteria in your colon will!
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result: ‘copious amounts’* of gas (CO2, methane, H2)
*Wikipedia’s descriptor
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Lactose in humans
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Who’s a mutant: those of you that can digest lactose, or those
that cannot?
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Better way to look at it is ‘lactase persistence’: the continued
ability to produce lactose-digesting enzymes
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“Ancestral” state: only babies need digest lactose b/c primary
source is mother’s milk
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“Derived” state: hey! I think I’ll suck on a cow/camel/goat teat!
(ewww!)
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So: who’s the mutant?
What’s in a gene?
Promoter
Controls
‘regulatory region’
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Go!
Product instructions
‘coding sequence’
A ‘gene’ is…
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instructions for what to make (‘coding sequence’
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instructions about where, when, how much to make
(specified by the regulatory regions)
Changes in any of these can give rise to changes in
appearance--phenotype
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Whence milk-induced
gases?
How did humans ‘learn’ (genetically) to drink milk?
How many times was this discover made?
Where? When?
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Caveat!
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This is ongoing research
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So we’re discussing preliminary results based on initial
datasets
Whodunnit? Smoking guns
Shown: DNA sequences with points of variability marked
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Smoking & non-smoking
guns
LP
sequences
LNP
sequences
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Whodunnit? Smoking guns
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Contrasting hypotheses
Single
origin
All lacexpressors
will have
same
change(s)
Cause of
change will
be common
to all
sequences
Occam:
Simplest = most
likely
Multiple
origins
All lacexpressors
will NOT
have same
change(s)
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Camel or cow milk? Yes.
Human
(chimpanzee sequence)
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And it goes like this...
“This result would justify the hypothesis that the
European T13910 and East African G13907 LP
alleles might have arisen because of a common
domestication event of the cattle whereas the
C3712- G13915 allele in Arabia most likely arose
due to the separate domestication event of camels.”
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Concept: mutation clock
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Things fall apart
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Some things are irrelevant
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Those things can be reasonably be presumed to fall apart at
constant rate
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Calibrate to reliable externals: fossil record, ancestries,
migrations… and you get the mutation clock
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Do wild animals resemble
cats, dogs, cattle?
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OK, maybe cats...
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Where did these docile, man-serving little blessings come
from?
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The same place as corn, broccoli, tomatoes…
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We made that
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Domestication
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http://www.spiegel.de/international/zeitgeist/neolithic-immigration-how-middle-eastern-milk-drinkers-conqueredeurope-a-723310.html
References (not trivial!)
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Blue eyes
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“Blue eye cool in humans may be caused by a perfectly associated
founder mutation in a regulatory element located within the HERC2
gene inhibiting OCA2 expression”
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Human Genetics 123:177 2008
Milk
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“Independent Introduction of Two Lactase-Persistence Alleles into
Human Populations Reflects Different History of Adaptation to Milk
Culture”
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American Journal of Human Genetics 82: 52-72 2008
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Resources
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HHMI: lactase movie
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http://www.hhmi.org/biointeractive/evolution/Lactase_Regulation/01.html