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Transcript
1
Does milk make you
gassy?
Why/why not?
What’s normal? Which the ‘discovery’?
I see dead people:
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
2
Information => Thinking
❖
Consider Tamiflu predictions
❖
IF resistance precedes stability, resistance should be older
❖
❖
3
should be ‘deeper branch’ + several subsets are stable
IF stability precedes resistance…
❖
stability should be the deeper branch w/ resistance
‘branchlets’
√
4
What’s milk got?
❖
‘milk sugar’ = lactose =
http://commons.wikimedia.org/wiki/File:Alpha-lactose-from-xtal-3D-balls.png
E. coli & lactose
❖
In Escherichia coli (E. coli, the gut bacterium), lactose ‘decisions’
are an hour-to-hour thing
❖
How/why does it make these decisions?
5
What’s in a gene?
Promote
r
Controls
‘regulatory
region’
❖
❖
Go!
Product instructions
‘coding sequence’
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
6
7
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 entire lifespan
8
You & lactose
❖
For millennia it was a sensible infancy vs. adulthood thing
❖
❖
If you don’t digest it… gut bacteria in your colon will!
❖
❖
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
❖
lactase
This will entail allowing researchers to stare at people’s genes
*Wikipedia’s descriptor
Summary: lactose in humans
9
❖
Heard of ‘lactose intolerance’? It’s the old normal!
❖
Alternative = ‘lactase persistence’: production of lactose-digesting enzymes
into adulthood
❖
Ancestral: 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 (ewww!)
❖
So: who’s the mutant?
10
Whence milk-induced
gases?
How did humans ‘discover’ (genetically) how to drink milk?
How many times was this discovery made?
Where? When?
11
Caveat!
❖
This is ongoing research
❖
So we’re discussing preliminary results based on initial
datasets
❖
TERMS:
❖
LNP non-Persistence (LNP, the ‘ancestral’ state)
❖
Lactase Persistence (LP, the ‘derived’ state)
Whodunnit? Smoking guns
Shown: DNA sequences with points of variability
marked
12
Smoking & non-smoking
guns
13
LP
sequence
s
LNP
sequence
s
Which mutations could be causal: lead to LNP phenotype?
Whodunnit? Smoking guns
14
15
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
16
Circle: large
group of people
Green:
digesters
Blue: nte, position
Red: causes
LP
(chimpanzee
sequence)
17
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
❖
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
18
Do 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
19
Domestication
20
http://www.spiegel.de/international/zeitgeist/neolithic-immigration-how-middle-eastern-milk-drinkers-conqueredeurope-a-723310.html
References (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
21
22
Resources
❖
HHMI: lactase movie
❖
http://www.hhmi.org/biointeractive/evolution/Lactase_Regulation/01.html