Download - Pop Genomics Adaptation 2
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Popula'onGenomicsofHumanAdapta'on,Part2
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Tes'ngForAdap'veEvolu'on
1) Ka/Ks>12) Ka/Ks>Pa/Ps
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Tes'ngForAdap'veEvolu'on
1) Ka/Ks>12) Ka/Ks>Pa/Ps
-BOTH METHODS REQUIRE RECURRENT ADAPTIVE EVOLUTION
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Tes'ngForAdap'veEvolu'on
1) Ka/Ks>12) Ka/Ks>Pa/Ps
-BOTH METHODS REQUIRE RECURRENT ADAPTIVE EVOLUTION -PICK UP GENES SUBJECT TO RECURRENT ADAPTATION, E.G. IMMUNITY AND REPRODUCTIVE GENES
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Tes'ngForAdap'veEvolu'on
1) Ka/Ks>12) Ka/Ks>Pa/Ps
-BOTH METHODS REQUIRE RECURRENT ADAPTIVE EVOLUTION -PICK UP GENES SUBJECT TO RECURRENT ADAPTATION, E.G. IMMUNITY AND REPRODUCTIVE GENES -WHAT ABOUT UNIQUE EVENTS OF ADAPTIVE EVOLUTION?
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Tes'ngForAdap'veEvolu'on
1) Ka/Ks>12) Ka/Ks>Pa/Ps
-BOTH METHODS REQUIRE RECURRENT ADAPTIVE EVOLUTION -PICK UP GENES SUBJECT TO RECURRENT ADAPTATION, E.G. IMMUNITY AND REPRODUCTIVE GENES -WHAT ABOUT UNIQUE EVENTS OF ADAPTIVE EVOLUTION? -WHAT ABOUT RECENT POSITIVE SELECTION ACTING WITHIN HUMAN POPULATIONS (local adaptation)?
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Tes'ngForAdap'veEvolu'on
1) Ka/Ks>12) Ka/Ks>Pa/Ps3) NEUTRALPOLYMORPHISM!
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EffectofPosi'veSelec'ononNEUTRALPOLYMORPHISM
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EffectofPosi'veSelec'ononNEUTRALPOLYMORPHISM
Neutral variation is reduced with positive selection
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EffectsofPosi'veSelec'ononNeutralPolymorphism
increase in linkage disequilibrium
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EffectsofPosi'veSelec'ononNeutralPolymorphism
shift in SNP frequencies
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EffectsofPosi'veSelec'ononNeutralPolymorphism
Increased differentiation among populations
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Posi'veselec'oneffects
1) Reduceddiversity2) shiPsinSNPfrequencies(excesslow
frequency)3) Increaseinlinkagedisequilibrium4) increaseinpopula'ondifferen'a'on
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Dis'nguishingNaturalSelec'onvs.Demographichistory:Genome-widepa\ernsofdiversity
• demographiceffectsshouldactgenome-wide,inaconsistentmanner
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Dis'nguishingNaturalSelec'onvs.Demographichistory:Genome-widepa\ernsofdiversity
• demographiceffectsshouldactgenomewide,inaconsistentmanner
• naturalselec'oncausesinconsistenciesamonggenesintheirpa\ernsofdiversity
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Dis'nguishingNaturalSelec'onvs.Demographichistory:Genome-widepa\ernsofdiversity
• demographiceffectsshouldactgenomewide,inaconsistentmanner
• naturalselec'oncausesinconsistenciesamonggenesintheirpa\ernsofdiversity
• challenge:howcanweusethisprincipletounderstandtheroleofselec'onvs.demographyonpa\ernsofdiversity?
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Dis'nguishingNaturalSelec'onvs.Demographichistory:Genome-widepa\ernsofdiversity
• demographiceffectsshouldactgenomewide,inaconsistentmanner
• naturalselec'oncausesinconsistenciesamonggenesintheirpa\ernsofdiversity
• challenge:howcanweusethisprincipletounderstandtheroleofselec'onvs.demographyonpa\ernsofdiversity?
characterizegenomicdistribu'onofpa\ernsofgene'c
diversity
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Dis'nguishingDemographyandSelec'on
• Inagenomiccontext,cantheresultsbeexplainedbyasinglehistoricalmodel,orarethereinconsistenciesacrossgenesintheirhistory?
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SignalofPosi'veSelec'on:ExampleofFOXP2
• muta'onsingenewithinhumansknowntoconferspecificaffectsonlanguageaquisi'on/grammarabili'es
• firstgenepossiblyimplicatedindevelopmentofhumanlanguageability
• twoaminoaciddifferencesfromchimpanzees,onepossiblyfunc'onal
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Enard et al Nature 418, 869-872(22 August 2002)
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Pa\ernsofDiversityatFOXP2
• unusualexcessoflow-frequencypolymorphisms(only1in315referencegenesshowedsuchanextremeexcess)
• modelingtheselec'vesweepconsistentwithselec'onhappeninginthelast200,000years
Enard et al Nature 418, 869-872(22 August 2002)
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Evolu'onofSkinPigmenta'on:LocalAdapta'onAssociatedWithUVradia'on
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Evolu'onofSkinPigmenta'on:LocalAdapta'onAssociatedWithUVradia'on
Annual Mean UVB Intensity
Jablonski and Chaplin PNAS May 11, 2010 vol. 107 no. Supplement 2 8962-8968
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Tradeoffsassociatedwithlightanddarkpigmenta'on
Jablonski and Chaplin PNAS May 11, 2010 vol. 107 no. Supplement 2 8962-8968
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TradeoffsassociatedwithSkinpigmenta'on
• HighUVradia'on:interfereswithfolate,selectsforincreasedpigmenta'on
• lowUVradia'on:reducesvitaminDsynthesis,selectsforreducedpigmenta'on
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Posi'veSelec'ononSkinPigmenta'on
-SLC24A5 one of approx. 10 genes implicated in pigmentation -reduction in polymorphism in European population -includes one of only two fixed differences between European and East Asian population samples
Lamason et al Science 16 December 2005: Vol. 310 no. 5755 pp. 1782-1786
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Scanning the Genome For Positive Selection/Adaptive Fixations
Rasmus Nielsen, UC Berkeley
-CLR statistic: compares probability that a region has its own SNP frequency distribution compared with the probability that it’s part of the genome-wide distribution
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Williamson et al (PLoS Genet. 2007 Jun;3(6):e90. Epub 2007 Apr 20)
Evidence for Adaptive Evolution in Pigmentation Genes
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Scanning the Genome For Positive Selection/Adaptive Fixations
-Williamson et al (PLoS Genet. 2007 Jun;3(6):e90. Epub 2007 Apr 20) Identified 101 regions showing strong signature of selection -genes under positive selection included pigmentation genes, immunity genes, olfactory receptors -as much as 10% of genome linked to regions subject to selective sweeps??
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Whataboutincompletesweeps?
• veryrecentposi'veselec'onandlocaladapta'onmayoPenNOTshowfixa'onevents
• scansforallelesathighfrequencywithlowdiversity
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EffectsofPosi'veSelec'ononNeutralPolymorphism
increase in linkage disequilibrium
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SignalsofongoingPosi'veSelec'on
Advantageous allele at high frequency, found on only one genomic background
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Mutations, Phenotype, and fitness: e.g. of G6PD
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Mutations, Phenotype, and fitness: e.g. of G6PD
DNA B GTG AAT CTA TGTA A- ATG GAT CTG TGTG
protein (allozymes)
B A-
phenotype B ‘wild type’ A- reduced enzyme activity/resistance to malaria
+
-
Val Asn Leu Met Asp Leu
negative
neutral
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RecentPosi'veSelec'onatG6PDlocus
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LactasePersistence:Gene/CultureCoevolu'on
• Lactasegenetypicallydown-regulatedinadults• pastoralculturesshowlactosetoleranceintoadulthood
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SignalsofPosi'veSelec'ononLactasePersistence
Bersaglieri et al, American Journal of Human Genetics Volume 74, Issue 6, June 2004, Pages 1111-1120
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• independentevolu'onoflactosetoleranceinAfricaandEurasia
ConvergentEvolu'onofLactasePersistence
Tishkoff et al Nature Genetics 39, 31 - 40 (2006)
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SignatureofPosi'veSelec'ononLactasePersistenceinbothAfrica
andEurasia
-persistence allele shows very low diversity despite being common =high linkage disequilibrium -diversity patterns consistent with selective sweep in past 7000 years
Tishkoff et al Nature Genetics 39, 31 - 40 (2006)
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Genome-WideScanforRecentPosi'veSelec'on
Jonathan Pritchard, University of Chicago
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Genome-WideScansforPosi'veSelec'on
Voight et al PLoS Biol. 2006 March; 4(3): e72.
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WhatGenesShowEvidenceforposi'veselec'on?
• reproduc'on:Spermmo'lity,spermandeggviability,femaleimmuneresponsetosperm
• skinpigmenta'on-fourgenesshowevidenceforrecentposi'veselec'oninEuropeanpopula'ons
• diet:carbohydratemetabolism,processingoffa\yacids
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YietalScience2July2010:Vol.329no.5987pp.75-78
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Fig. 1 Two-dimensional unfolded site frequency spectrum for SNPs in Tibetan (x axis) and Han (y axis) population samples.
X Yi et al. Science 2010;329:75-78
Published by AAAS
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Fig. 2 Population-specific allele frequency change.
X Yi et al. Science 2010;329:75-78
Published by AAAS
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GenesSubjecttoAdapta'ontoHighEleva'on
-EPAS1: transcription factor involved in hypoxia response -associated with lower hemoglobin and lower erythrocyte counts at high elevation