Download E. coli

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Does milk make you
gassy?
Why/why not?
What’s normal? Which the ‘discovery’?
I see dead people:
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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Information => Thinking
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Consider Tamiflu predictions
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IF resistance precedes stability, resistance should be older
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should be ‘deeper branch’ + several subsets are stable
IF stability precedes resistance…
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stability should be the deeper branch w/ resistance
‘branchlets’
√
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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
E. coli & lactose
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In Escherichia coli (E. coli, the gut bacterium), lactose ‘decisions’
are an hour-to-hour thing
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How/why does it make these decisions?
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What’s in a gene?
Promote
r
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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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 entire lifespan
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You & lactose
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For millennia it was a sensible infancy vs. adulthood thing
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If you don’t digest it… gut bacteria in your colon will!
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Ability to digest milk was wasteful in adults!!!
result: ‘copious amounts’* of gas (CO2, methane, H2)
I will now argue that humans evolved extended
expression several times
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lactase
This will entail allowing researchers to stare at people’s genes
*Wikipedia’s descriptor
Summary: lactose in humans
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Heard of ‘lactose intolerance’? It’s the old normal!
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Alternative = ‘lactase persistence’: production of lactose-digesting enzymes
into adulthood
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Ancestral: 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 (ewww!)
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So: who’s the mutant?
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Whence milk-induced
gases?
How did humans ‘discover’ (genetically) how to drink milk?
How many times was this discovery 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
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TERMS:
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LNP non-Persistence (LNP, the ‘ancestral’ state)
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Lactase Persistence (LP, the ‘derived’ state)
Whodunnit? Smoking guns
Shown: DNA sequences with points of variability
marked
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Smoking & non-smoking
guns
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LP
sequence
s
LNP
sequence
s
Which mutations could be causal: lead to LNP phenotype?
Whodunnit? Smoking guns
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Contrasting hypotheses
Single
origin
Multiple
origins
Cause of change will be
common to all
sequences
All lac-expressors will
have same change(s)
Occam:
Simplest = most
likely
All lac-expressors will
NOT have same
change(s)
Camel or cow milk? Yes.
Human
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Circle: large
group of people
Green:
digesters
Blue: nte, position
Red: causes
LP
(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 C3712G13915 allele in Arabia most likely arose due to the
separate domestication event of camels.”
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