1 Does milk make you gassy?Why/why not? • What’s normal? Which the ‘discovery’?
2 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
3 Information => Thinking • Consider Tamiflu predictions • IF resistance precedes stability, resistance should be older • 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
5 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?
Promoter Go! 6 What’s in a gene? Controls ‘regulatory region’ Product instructions ‘coding sequence’ • A ‘gene’ is… • instructions for what to make (‘coding sequence’ • instructions about where, when, howmuch to make (specified by the regulatoryregions) • Changes in anyof thesecan give rise to changes in appearance--phenotype
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 • Ability to digest milk was wasteful in adults!!! • If you don’t digest it… gut bacteria in your colon will! • result: ‘copious amounts’* of gas (CO2, methane, H2) • I will now argue that humans evolved extended lactase expressionseveral times • This will entail allowing researchers to stare at people’s genes *Wikipedia’s descriptor
9 Summary: lactose in humans • 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)
12 Whodunnit? Smoking guns Shown: DNA sequences with points of variability marked
13 Smoking & non-smoking guns LP sequences LNP sequences Which mutations could be causal: lead to LNP phenotype?
14 Whodunnit? Smoking guns
Cause of change will be common to all sequences Multiple origins Single origin 15 Contrasting hypotheses Occam: Simplest = most likely All lac-expressors will have same change(s) All lac-expressors will NOT have same change(s)
Green: digesters 16 Camel or cow milk? Yes. Red: causes LP Circle: large group of people Human Blue: nte, position (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 C3712- G13915 allele in Arabia most likely arose due to the separate domestication event of camels.”
18 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
19 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
20 Domestication http://www.spiegel.de/international/zeitgeist/neolithic-immigration-how-middle-eastern-milk-drinkers-conquered-europe-a-723310.html
21 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
22 Resources • HHMI: lactase movie • http://www.hhmi.org/biointeractive/evolution/Lactase_Regulation/01.html