Activity
Got Lactase? The Co-evolution of Genes and Culture
Student Handout
PATTERNS IN THE DISTRIBUTION OF LACTASE PERSISTENCE
INTRODUCTION
Atsomepointafterweaning,mosthumansaroundtheworldlosetheabilitytodigestlactose,themainsugar
foundinmilk.Lactoseisbrokendownbytheenzymelactase,whichisproducedbycellsliningthesmall
intestine.Individualsthatarelactoseintolerant,orlactasenonpersistent,nolongerproducethisenzyme.
However,insomepartsoftheworld,mostoftheadultpopulationcontinuestodigestlactose.Thesepeopleare
calledlactosetolerantorlactasepersistent,becauseexpressionofthelactasegenepersistsbeyondchildhood.
Inpeoplethatarelactoseintolerant,thelactasegenegets“turnedoff”sometimeafterbreastfeedingstops,
whereasinpeoplewhoarelactosetolerantthelactasegeneispermanently“turnedon.”Scientistshave
discoveredthatthegeneremains“on”duetomutationsthatarenotinthelactasegeneitselfbutinacontrol
regionnearit.
Lactosetolerance(orlactasepersistence)isfoundinso-calledpastoralistpopulations.About7,500to9,000
yearsago,certaingroupsofpeoplebegandomesticatingcattleanddrinkingtheirmilk.Insuchcultures,the
lactase-persistencetraitincreasedinfrequencyovertime.
Youwillexplorethegeographicdistributionoflactasepersistencearoundtheworldbyanalyzingrealdata
collectedbyscientiststhatwillhelpyouidentifypatterns.
MATERIALS
•
•
•
•
•
GeneticDataTable
PhenotypeDataTable
PieChartStencilsorcirclestickers
WorldMap(supplementalhandoutfrom
instructor)
Calculator(oneperstudent)
•
•
•
•
•
Twocoloredpencils
Scissors
Gluestickortape
Computer/referencesforgeographyresearch
QuickGuide:MeasuringanIndividual’sAbilityto
DigestLactose(optional)
PROCEDUREPART1:ANALYZINGTHEDATATABLES
1.
ViewthefilmGotLactase?TheCo-evolutionofGenesandCulture,payingparticularattentiontothe
distributionsandfrequenciesofpeoplewhoarelactoseintolerant(lactasenonpersistent)andlactose
tolerant(lactasepersistent)invariouspopulationsaroundtheworld.
2.
ExaminetheGeneticDataTable.ThegeneticdatawerecollectedbysequencingDNAnearthelactasegene.
Scientistshaveidentifiedatleastfourmutationsnearthelactasegeneassociatedwiththelactasepersistencetrait.Thesemutationsresultedintheformationofnewalleles.Theallelesthatcauselactase
persistencearecalledlactase-persistencealleles,andtheyactinadominantfashiontothenonpersistence
alleles.Soapersononlyneedsonecopyofalactase-persistencealleletoshowthetrait.Thenumberof
peoplewhohadoneortwocopiesofalactase-persistenceallelewerecountedandrecordedinthecolumn
“#Peoplewithalactase-persistenceallele.”
3.
Calculatethefrequencyoflactasepersistenceineachhumanpopulationsampled.Recordthefrequencies
(expressedasadecimalandroundedtothehundredthsplace)inthecolumnlabeled“Lactase-persistence
frequency.”(Youmaybeaskedtoworkingroupsorasaclass.)
4.
ExaminethePhenotypeDataTable.Thephenotypedatawerecollectedusingteststhatmeasuredan
individual’sabilitytodigestlactose.Somestudiesusedabloodglucosetest,whileothersusedahydrogen
www.BioInteractive.org
PublishedApril2017
Page1of11
Activity
Got Lactase? The Co-evolution of Genes and Culture
Student Handout
breathtest.Tolearnmoreaboutthesetwotests,readtheoptionalhandout“QuickGuide:Measuringan
Individual’sAbilitytoDigestLactose”onpage11.
5.
InthePhenotypeDataTable,calculatethefrequencyoflactasepersistenceineachpopulation.Recordthe
frequenciesinthecolumnlabeled“Lactase-persistencefrequency.”(Youmaybeaskedtoworkingroupsor
asaclass.)
QUESTIONSPART1:DATAANALYSIS
6. LookattheSomalipopulationinEthiopia(A)inthegeneticdataset(page8).Answerthefollowing
questions:
a. Howmanypeopleweretestedinthestudy?
b. Howmanypeoplehaveatleastonealleleassociatedwiththelactase-persistencetrait?
c. Howmanypeopledidnothaveallelesassociatedwiththelactase-persistencetrait?
d. CalculatethefrequencyofpeopleintheSomalistudywhodidnothaveoneofthefouralleles
associatedwiththelactase-persistencetrait.(Showyourwork.)
e. AssumethatthecalculatedfrequencywasanaccuraterepresentationoftheentireSomalipopulation.
ThepopulationofSomaliaisaround10million.Approximatelyhowmanypeopleintotalwouldyou
expecttohaveatleastonealleleassociatedwiththelactase-persistencetrait?(Showyourwork.)
7. Usingthephenotypedatatable(page9),lookattheSomalipopulation(A)inEthiopia.Answerthefollowing
questions:
a. Howmanypeopleweretestedinthephenotypestudy?
b. Howmanypeopletestedpositivefortheabilitytodigestlactose?
c. Howmanypeoplewereunabletodigestlactose?
d. CalculatethefrequencyofpeopleintheSomalistudywhotestednegativeforthelactase-persistence
phenotype.(Showyourwork.)
www.BioInteractive.org
PublishedApril2017
Page2of11
Activity
Got Lactase? The Co-evolution of Genes and Culture
Student Handout
e. Whatdidthescientistsmeasuretocollectthegeneticandphenotypedata?Inotherwords,inwhatway
dothetwodatasetsdiffer?
8.
Fromthedatatables,recordthelactase-persistence(LP)frequenciesandreferencesforthefollowing
population:
POPULATION
Hungary
(Hungarians)(X)
DATATYPE
LPFREQUENCY
REFERENCES
Geneticdata
Phenotypedata
a. Writedowntwodifferencesyounoticeaboutthedata.
b. Providetworeasonswhythefrequenciesoflactasepersistencemightbedifferentwhencomparing
geneticandphenotypedataintheHungarianpopulation(X).(Hint:Thinkofboththemethodsusedto
determinethesefrequenciesandthebiologicaldifferencesbetweengenotypeandphenotype
frequencies.)
9.
Inageneticstudy,1876individualsweresampledinFinland,whereas58peopleweresampledinFrance.
(Finland’stotalpopulationin2008was5.3million,whileFrance’spopulationin2004was60.4million.)
a. Whichdatasetprobablyrepresentsthecountrymoreaccurately?
b. Whattwoquestionswouldyoulikeansweredaboutthesamplestohelpyoufeelcomfortablethatthey
accuratelyrepresentthepopulationofaparticularcountry?
www.BioInteractive.org
PublishedApril2017
Page3of11
Activity
Got Lactase? The Co-evolution of Genes and Culture
Student Handout
10. Comparingthegeneticdatatothephenotypedata,identifyapatternyouobserveinthetwodatasetsfor
thethreepopulationsfromSudan(F,G,H).
11. Usingthegeneticinformationprovided,whatdothelactase-persistencefrequenciesfromthepopulations
fromSenegal(Wolof-D),Sudan(Dinka-G),andJapan(Japanese-N)haveincommon?
12. Thelactase-persistencephenotypefrequencydatafromthesethreepopulationsrangefrom25%to51%.
Basedonyourknowledgeofmoleculargenetics(DNA,genes,geneexpression),whatmightbeareasonfor
thisdifference?
13. Basedongeneticandphenotypedata,developahypothesisabouttheculturalpracticesregarding
domesticatinglivestockandconsumingmilkofthepopulationssampledinUganda(I),China(P),andPapua
NewGuinea(R).
14. TheDinkapeopleofSudan(G)areknownasagropastoralists.Theydependonagricultureduringtherainy
seasonandlivestockherdinganddomesticationduringthedryseason.Accordingtothestudy,theDinka
peoplesampledhada0%frequencyoflactasepersistencewhenlookingatthegeneticdata,whichisnot
consistentwiththeiragropastoralistculture.Whatmightbealimitationtothisparticularresearchstudy?
PROCEDUREPART2:MAPPINGTHEALLELEFREQUENCIES
Tomapthefrequenciesforlactasepersistenceandnonpersistence,createaminipiechartforeachpopulation.
NoticethatthefirstcolumnoftheGeneticDataTablehaslettersdenotingeachpopulation.Thepiechart
stencilsonpage10alsoincludelettersinthecenterofeachcircle.Eachofthepiechartstencilscorrespondsto
theletteredpopulationintheGeneticDataTable.
Note:Theexactprocedurewillvaryfromclasstoclass.Forexample,yourinstructormayhaveyouworkononly
afewofthepiechartsorallofthem,workinginsmallgroupsorasaclass.
www.BioInteractive.org
PublishedApril2017
Page4of11
Activity
Got Lactase? The Co-evolution of Genes and Culture
Student Handout
15. Choosetwodifferentcolorpencils.Designateonecolorforlactasepersistenceandtheotherforlactase
nonpersistence.
Frequency
Lactasepersistence
Lactasenonpersistence
Color
16. Usingthepiechartstencilsandcoloredpencils,colortheappropriatepiecharttorepresentthelactase
persistenceandnonpersistencefrequencyforeachpopulationfromtheGeneticDataTable.(Besureto
matchtheletterofeachpopulationtotheletteronthepiechartstencil.)
Example(Ex)PieChart
15%
LactasePersistence
LactaseNonpersistence
85%
17. Cutoutallthecoloredpiecharts.(Theydon’tneedtolookpretty.)
18. Useareliablereference(i.e.,awebsite,socialstudiestextbook,orareferenceprovidedbyyourteacher)to
placethepiechart(s)intheappropriatelocationsontheprovidedworldmap.(DoNOTtapeorglue.)
19. Onceallthepiechartsareplacedonthemap,spacethemsothatyoucanseeeachoneincludingtheletters.
Neatlytapeorgluethemtotheworldmap.Besuretoaddatitleandkeytoyourmap.
QUESTIONSPART2:MAPANALYSIS
20. Lookingattheglobaldistributionofpiechartsonyourmap,writethreeclaimsthatyoucouldmakeabout
theworldwidedistributionoflactasepersistence.Notetheevidencethatsupportsyourclaimand
alternativeexplanationsordatathatdonotsupportyourclaim.(Forexample,inEurope,youcouldmakea
claimabouthowthepatternoflactase-persistence/nonpersistencefrequenciesrelatestolatitude.)
Claim1:
Claim2:
Claim3:
21. Whatdoyounoticeaboutthelactase-persistencefrequenciesoftheMaasaipeopleinKenya(B)andthe
Sengwerpeople,alsoinKenya(C)?
a. Basedontheinformationpresentedinthefilm,whatcouldhaveaccountedforthisdifference?Explain
youranswer.
www.BioInteractive.org
PublishedApril2017
Page5of11
Activity
Got Lactase? The Co-evolution of Genes and Culture
Student Handout
22. LookatthegeneticdataforthetwopopulationsfromEngland(S,T)andthetwopopulationsfromItaly(Y,
Z).WhatdoyounoticewhenyoucompareStoTandYtoZwithineachcountry?Whatquestionor
questionsdoesthiscomparisonraiseforyou?
23. WhatdoyounoticewhenanalyzingthegeneticdataforNorthernEuropeandthoseforEast
Asia/Australasia?Whatreasoncouldtherebeforthedifferenceyouobserve?
24. FindtheallelefrequencypiechartinChinafortheHanpeople(P).TheHanpeoplemakeup92%of
mainlandChina’spopulationandroughlyone-fifthoftheworld’spopulation.Ofthe200peoplesampled,
whatpercentagewaspredictedtobelactoseintolerant?
Astudypublishedin2009showsanincreaseinmilkconsumptionamongtheChinesepeople.Seethegraph:
Percapitaconsumptionofdairyproductsinruralandurbanhouseholds
Source:Chinesestatisticalyearbook
www.BioInteractive.org
PublishedApril2017
Page6of11
Activity
Got Lactase? The Co-evolution of Genes and Culture
Student Handout
25. Usingthegraphon the previous page,predicthowthegeneticdataforlactase-persistencefrequencymight
change ifthe samepopulationissampledagainin1000years.Explainyourprediction,notingwhat(ifany)
selective pressures would be present.
26. ThemainfoodsourcesoftheBantupeopleofUganda(I)arematoke(afruitinthebananafamily),eggs,fish,
beans,nuts,beef,chicken,goats,andvariousfruitsandvegetables.Explainhowthedatapresentedinthis
activityeithersupportordonotsupportwhatyounowknowabouttheirculturaldiet.
27. Inafewsentences,supporttheclaimthatlactasepersistenceisagoodexampleofgene/cultureco-
evolution.Yourexplanationshouldincludeseveralpiecesofevidence.
www.BioInteractive.org
PublishedApril2017
Page7of11
GeneticData
Dataindicatewhetherapersoninthesamplehasatleastonecopyofthelactase-persistenceallele.
#Peoplewith
Lactase#People
lactasepersistence
sampled(n) persistenceallele frequency
Reference
Continent/
Region
Country
Population
A
Africa
Ethiopia
Somali
74
22
Ingrametal.(2009)Hum.Gen.124,579.
B
Africa
Kenya
Maasai
64
54
Tishkoffetal.(2007)Nat.Genet.39,31.
C
Africa
Kenya
Sengwer
32
4
Tishkoffetal.(2007)Nat.Genet.39,31.
D
Africa
Senegal
Wolof
118
0
Ingrametal.(2009)Hum.Gen.124,579.
E
Africa
SouthAfrica
Xhosa
109
27
Torniainenetal.(2009)BMCGenet.10,31.
F
Africa
Sudan
BeniAmer
162
73
Ingrametal.(2009)Hum.Gen.124,579.
G
Africa
Sudan
Dinka
18
0
Tishkoffetal.(2007)Nat.Genet.39,31.
H
Africa
Sudan
Jaali
172
46
Ingrametal.(2009)Hum.Gen.124,579.
I
Africa
Uganda
Bantu
44
0
Mulcareetal.(2004)Am.J.Hum.Genet.74,1102.
J
Africa
Tanzania
Burunge
36
22
Tishkoffetal.(2007)Nat.Genet.39,31.
K
Africa
Tanzania
Maasai
38
26
Tishkoffetal.(2007)Nat.Genet.39,31.
L
Asia
Afghanistan
Tadjik
98
19
Mulcare(2006)London:UniversityofLondonPhD.
M
Asia
India
Indian
68
17
Mulcare(2006)London:UniversityofLondonPhD.
N
Asia
Japan
Japanese
62
0
Bersaglierietal.(2004)Am.J.Hum.Genet.74,1111.
O
Asia
Russia
Udmurt
60
33
Enattahetal.(2008)Am.J.Hum.Genet.82,57.
P
Asia
China
Han
200
0
Enattahetal.(2008)Am.J.Hum.Genet.82,57.
Q
Asia
China
Mongol
82
8
Sunetal.(2007)AsiaPac.J.Clin.Nutr.16,4.
R
Australasia
PapuaNewGuinea
Papuan
34
0
Bersaglierietal.(2004)Am.J.Hum.Genet.74,1111.
S
Europe
England
English,northern
1168
1098
DaveySmithetal.(2009)Eur.J.HumanGen.,17,357-367.
T
Europe
England
English,southeastern
947
862
DaveySmithetal.(2009)Eur.J.HumanGen.,17,357-367.
U
Europe
Finland
Finn
1876
1538
Enattahetal.(2008)Am.J.Hum.Genet.82,57.
V
Europe
France
French
58
39
Bersaglierietal.(2004)Am.J.Hum.Genet.74,1111.
W
Europe
Greece
Greek
100
17
Anagnostouetal.(2009)Am.J.Hum.Biol.21,217.
X
Europe
Hungary
Hungarian
110
95
Nagyetal.(2009)Eur.J.Clin.Nutr.63,909.
Y
Europe
Italy
NorthernItalian
28
17
Bersaglierietal.(2004)Am.J.Hum.Genet.74,1111.
Z
Europe
Italy
Sardinian
153
21
Anagnostouetal.(2009)Am.J.Hum.Biol.21,217.
AA
Near/MiddleEast
Jordan
Jordanian
112
22
Enattahetal.(2008)Am.J.Hum.Genet.82,57.
BB
Near/MiddleEast
Turkey
AnatolianTurk
98
6
Mulcare(2006)London:UniversityofLondonPhD.
CC
Near/MiddleEast
SaudiArabia
Bedouin
94
69
Ingrametal.(2009)Hum.Gen.124,579.
DD
Near/MiddleEast
SaudiArabia
Arab
248
206
Enattahetal.(2008)Am.J.Hum.Genet.82,57.
Source:GlobalLactasePersistenceAssociationDatabase,http://www.ucl.ac.uk/mace-lab/resources/glad
www.BioInteractive.org
Published April 2017
Page8of11
PhenotypeData
Lactase#peopletested
#people
positiveforlactase persistence
sampled(n)
frequency
persistence
90
22
Continent/
Region
Country
Population
A
Africa
Ethiopia
Somali
B
Africa
Kenya
Maasai
26
23
Tishkoffetal.(2007)Nat.Genet.39,31.
C
Africa
Kenya
Sengwer
12
2
Tishkoffetal.(2007)Nat.Genet.39,31.
D
Africa
Senegal
Wolof
53
27
Arnoldetal.(1980)C.R.SeancesSoc.Biol.Fil.174,983.
E
Africa
SouthAfrica
Xhosa
17
3
Segaletal.(1983)Am.J.Clin.Nutr.38,901.
F
Africa
Sudan
BeniAmer
40
35
Bayoumietal.(1982)Am.J.Phys.Anthropol.58,173.
G
Africa
Sudan
Dinka
208
52
Bayoumietal.(1982)Am.J.Phys.Anthropol.58,173.
H
Africa
Sudan
Jaali
113
60
Bayoumietal.(1981)Hum.Genet.57,279.
I
Africa
Uganda
Bantu
17
1
Cooketal.(1966)Lancet1,725.
J
Africa
Tanzania
Burunge
16
6
Tishkoffetal.(2007)Nat.Genet.39,31.
K
Africa
Tanzania
Maasai
15
10
Tishkoffetal.(2007)Nat.Genet.39,31.
L
Asia
Afghanistan
Tadjik
79
14
Rahimietal.(1976)Hum.Genet.34,57.
M
Asia
India
Indian
100
36
Desaietal.(1970)IndianJ.Med.Sci.24,729.
N
Asia
Japan
Japanese
40
11
Yoshidaetal.(1975)Gastroenterol.Jpn.10,29.
O
Asia
Russia
Udmurt
30
18
Kozlov(1998)Int.J.CircumpolarHealth57,18.
P
Asia
China
Han
248
20
Yongfaetal.(1984)Hum.Genet.67,103.
Q
Asia
China
Mongol
198
24
Yongfaetal.(1984)Hum.Genet.67,103.
R
Australasia
Papuan
30
3
Jenkinsetal.(1981)Ann.Hum.Biol.8,447.
*
Europe
PapuaNew
Guinea
England
British
150
143
Fergusonetal.(1984)Gut25,163.
U
Europe
Finland
Finn
638
530
Jussila(1969)Ann.Clin.Res.1,199.
V
Europe
France
French
102
78
Cloarecetal.(1991)Gastroenterol.Clin.Biol.15,588.
W
Europe
Greece
Greek
600
330
Kanaghinisetal.(1974)Am.J.Dig.Dis.19,1021.
X
Europe
Hungary
Hungarian
535
337
Czeizeletal.(1983)Hum.Genet.64,398.
Y
Europe
Italy
NorthernItalian
208
102
Burgioetal.(1984)Am.J.Clin.Nutr.39,100.
Z
Europe
Italy
Sardinian
53
6
Melonietal.(1998)Ital.J.Gastroenterol.Hepatol.30,490.
Near/Middle
East
Near/Middle
East
Near/Middle
East
Near/Middle
East
Jordan
Jordanian
148
37
Hijazietal.(1983)Trop.Geogr.Med.35,157.
Turkey
AnatolianTurk
122
32
Flatzetal.(1986)Am.J.Hum.Genet.38,515.
SaudiArabia
Bedouin
21
17
Dissanayakeetal.(1990)Ann.SaudiMed.10,598.
SaudiArabia
Arab
109
47
Dissanayakeetal.(1990)Ann.SaudiMed.10,598.
AA
BB
CC
DD
Reference
Ingrametal.(2009)Hum.Gen.124,579.
Source:GlobalLactasePersistenceAssociationDatabase,http://www.ucl.ac.uk/mace-lab/resources/glad
www.BioInteractive.org
Published April 2017
Page9of11
Activity
Got Lactase? The Co-evolution of Genes and Culture
Student Handout
PieChartStencils
A
B
C
D
E
F
G
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z
AA
BB
CC
DD
www.BioInteractive.org
PublishedApril2017
Page10of11
Activity
Got Lactase? The Co-evolution of Genes and Culture
Student Handout
QUICKGUIDE:MEASURINGANINDIVIDUAL’SABILITYTODIGESTLACTOSE
“Mother’smilk”ispackedwiththeproteins,fats,andcarbohydratesthatsupportthegrowth,development,andsurvivalof
babymammals.Thesugarlactoseisthemaincarbohydrateinmilk.Lactosecanbecleavedintotwosimplersugars,glucose
andgalactose,bylactase,anenzymeproducedinthesmallintestine.Thetwosmallersugarsarereadilyabsorbedthough
theintestinalwallintothebloodstreamfordeliverytothecellsofthebody,wheretheyareusedforenergy.
Afterinfantmammalsareweaned
fromtheirmother’smilk,lactase
productionshutsdown,presumably
becauseitisnolongerneeded.This
conditioniscalledlactase
nonpersistence—meaningthat
productionofthelactaseenzymedoes
notpersistintoadulthood.The
generalconditionformammalsisnot
toconsumemilkafterweaningandto
belactasenonpersistent.Some
populationsofhumansareunusualin
thatadultscontinuetoconsumemilk
fromothermammals,suchascows.
Ifapersonwhoislactasenonpersistentdrinksmilk,undigestedlactosepassesfromthesmallintestinetothelarge
intestine,whereitisfermentedbybacteria.Fermentationproducesvariousgasesinthelargeintestine,whichcancause
abdominalpain,bloating,flatulence,anddiarrhea—allsymptomsoflactoseintolerance.Worldwide,mostadultsare
lactoseintolerant,althoughsomepeoplemaynotknowbecausetheirsymptomsaremild.Onlyaminorityofhumanadults
(35%oftheglobalhumanpopulation)continuestoproducelactaseintoadulthoodandcandrinkmilkwithoutany
problems.Theseindividualsaresaidtobelactasepersistentorlactosetolerant.
TestingMethods
Onewaytotestwhetherapersonislactasepersistentistomeasuretheirbloodglucoselevels.Intheshortfilm,Got
Lactase?TheCo-evolutionofGenesandCulture,thenarrator,Dr.SpencerWells,takesabloodglucosetesttodeducehis
lactasestatus.Ifthelactaseenzymeispresent,bloodglucoselevelsincreasewithin20to60minutesofdrinkingmilk.
Anothercommontestusedtodeterminewhethera
personislactasepersistentisthehydrogenbreath
test.Thistestmeasurestheamountofhydrogenina
person’sbreath.Undigestedlactoseisfermentedby
bacteriainthelargeintestineandproducesseveral
gases,includinghydrogen.Thesegasesexitthebody
throughtheanus;theycanalsobeabsorbedintothe
blood,circulatedtothelungs,andeliminated
throughthebreath.Ifalactasenonpersistentperson
consumeslactose,theamountofhydrogenintheir
breathwillgoupwhereastheamountofhydrogenin
thebreathofsomeonewhoislactasepersistentwill
staythesame.
www.BioInteractive.org
PublishedApril2017
Page11of11