1
Semester projects!❖ Miraculin paper based!
❖ Find a partner with same TA (needn’t be same section)
❖ You will
❖ Be supplied with suspicious red tablets!
❖ Be expected to support/refute a claim from the paper
❖ Read & reference >= 1 reference from the Miraculin paper as well as the paper itself
❖ Be awarded 3 point bonus for improving on the Dr. Pepper!!!
2
Midterm musings❖ How are bases & amino acids suited to their tasks?
❖ How does hemoglobin function as a machine?
❖ pH triggers
❖ DPG--how & why; fetal changes
❖ Cooperativity
❖ Periodic table: clues & progress
❖ siRNA: send a thief to catch a thief
❖ tamiflu: tracing lineages through mutations
❖ Blue eyes & milk drinking: single vs. multiple origins (hemo?)
3Does milk make you Does milk make you gassy?gassy?
Why/why not?Why/why not?
What’s normal? What’s the discover?What’s normal? What’s the discover?
*According to dictionary.com: the necessary changes have been *According to dictionary.com: the necessary changes have been mademade
4Key concept: DNA is historical record
❖ You got your genes at the Parent’s store
❖ So did they
❖ ad infinitum
❖ Conclude: Your genes are not your own. They are a copy of a copy of a copy of a copy…
❖ They contain a record of who (what) you were
5
What’s milk got?
❖ ‘milk sugar’ = lactose =
http://commons.wikimedia.org/wiki/File:Alpha-lactose-from-xtal-3D-balls.png
6
Imagine a normal mammal...
❖ not some bizarro cross-species-suckling human!
❖ ...where do you get milk?
❖ ...when do you get milk?
❖ when do you no longer get milk?
❖ Is it pointful to build milk-processing bioMachines (enzymes) for your entire life
7
If you don’t digest it...
❖ gut bacteria in your colon will!
❖ result: ‘copious amounts’* of gas (CO2, methane, H2)
*Wikipedia’s descriptor
8
Lactose in humans
❖ Who’s a mutant: those of you that can digest lactose, or those that cannot?
❖ Better way to look at it is ‘lactase persistence’: the continued ability to produce lactose-digesting enzymes
❖ “Ancestral” state: only babies need digest lactose b/c primary source is mother’s milk
❖ “Derived” state: hey! I think I’ll suck on a cow/camel/goat teat! (ewww!)
❖ So: who’s the mutant?
9
What’s in a gene?
❖ A ‘gene’ is…
❖ instructions for what to make (‘coding sequence’
❖ 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
Controls‘regulatory region’ Product instructions
‘coding sequence’
Go!Go!
Promoter
10
Whence milk-induced Whence milk-induced gases?gases?
How did humans ‘learn’ (genetically) to drink milk?How did humans ‘learn’ (genetically) to drink milk?How many times was this discover made?How many times was this discover made?
Where? When?Where? When?
11
Caveat!
❖ This is ongoing research
❖ So we’re discussing preliminary results based on initial datasets
12
Whodunnit? Smoking guns
Shown: DNA sequences with points of variability marked
13
Smoking & non-smoking guns
LNP sequences
LP sequences
14
Whodunnit? Smoking guns
15Contrasting hypotheses
Cause of Cause of change change will be will be
common common to all to all
sequencessequences
Occam:Occam:Simplest = Simplest = most likelymost likely
Single Single originorigin
Multiple Multiple originsorigins
All lac-All lac-expressors expressors will have will have
same same change(s)change(s)
All lac-All lac-expressors expressors will will NOT NOT
have same have same change(s)change(s)
16Camel or cow milk? Yes.
(chimpanzee sequence)
Human
17And 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.”
18Concept: mutation clock
❖ Things fall apart
❖ Some things are irrelevant
❖ Those things can be reasonably be presumed to fall apart at constant rate
❖ Calibrate to reliable externals: fossil record, ancestries, migrations… and you get the mutation clock
19Do wild animals resemble
cats, dogs, cattle?❖ OK, maybe cats...
❖ Where did these docile, man-serving little blessings come from?
❖ The same place as corn, broccoli, tomatoes…
❖ We made that
20Domestication
http://www.spiegel.de/international/zeitgeist/neolithic-immigration-how-middle-eastern-milk-drinkers-conquered-europe-a-723310.html
21References (not trivial!)
❖ Blue eyes
❖ “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”
❖ Human Genetics 123:177 2008
❖ Milk
❖ “Independent Introduction of Two Lactase-Persistence Alleles into Human Populations Reflects Different History of Adaptation to Milk Culture”
❖ American Journal of Human Genetics 82: 52-72 2008
22
Resources
❖ HHMI: lactase movie
❖ http://www.hhmi.org/biointeractive/evolution/Lactase_Regulation/01.html
