MuinaisDNA-katsaus

Luupiiri, Helsingin yliopisto, 14.11.2014

Marja Pirttivaara, FT, MBA

14.11.2014 Marja Pirttivaara 1

Esityksen fokus

• Lähtökohta: uteliaisuus

• Mitä ajankohtaista muinaisDNA-rintamalla?

• Kontaminaatio

• Haploryhmät ja DNA-vertailut

14.11.2014

Päivääniemen rautakautinen kalmisto, Lempäälä © Mika Pirttivaara

Marja Pirttivaara

Syksyn mielenkiintoisin muinaisDNA-julkaisu

Ancient human genomes suggest three ancestral populations for present-day Europeans. Nature. 2014 Sep 18;513(7518):409-13.

Lazaridis I, Patterson N, Mittnik A, Renaud G, Mallick S, Kirsanow K, Sudmant PH, Schraiber JG, Castellano S, Lipson M, Berger B, Economou C, Bollongino R, Fu Q, BosKI, Nordenfelt S, Li H, de Filippo C, Prüfer K, Sawyer S, Posth C, Haak W, Hallgren F, Fornander E, Rohland N, Delsate D, Francken M, Guinet JM, Wahl J, Ayodo G, BabikerHA, Bailliet G, Balanovska E, Balanovsky O, Barrantes R, Bedoya G, Ben-Ami H, Bene J, Berrada F, Bravi CM, Brisighelli F, Busby GB, Cali F, Churnosov M, Cole DE, Corach D, Damba L, van Driem G, Dryomov S, Dugoujon JM, Fedorova SA, Gallego Romero I, Gubina M, Hammer M, Henn BM, Hervig T, Hodoglugil U, Jha AR, Karachanak-Yankova S, Khusainova R, Khusnutdinova E, Kittles R, Kivisild T, Klitz W, Kučinskas V, Kushniarevich A, Laredj L, Litvinov S, Loukidis T, Mahley RW, Melegh B, Metspalu E, Molina J, Mountain J, Näkkäläjärvi K, Nesheva D, Nyambo T, Osipova L, Parik J, Platonov F, Posukh O, Romano V, Rothhammer F, Rudan I, Ruizbakiev R, Sahakyan H, Sajantila A, Salas A, Starikovskaya EB, Tarekegn A, Toncheva D, Turdikulova S, Uktveryte I, Utevska O, Vasquez R, Villena M, Voevoda M, Winkler CA, YepiskoposyanL, Zalloua P, Zemunik T, Cooper A, Capelli C, Thomas MG, Ruiz-Linares A, Tishkoff SA, Singh L, Thangaraj K, Villems R, Comas D, Sukernik R, Metspalu M, Meyer M, EichlerEE, Burger J, Slatkin M, Pääbo S, Kelso J, Reich D, Krause J.

http://www.ncbi.nlm.nih.gov/pubmed/25230663 (13.11.2014)

Marja Pirttivaara14.11.2014

Samankaltaisia artikkeleita?

Lazaridis et al: Ancient human genomes suggest three ancestral populations for present-day Europeans. Nature. 2014 Sep 18;513(7518):409-13.

Lisähaku PubMed filttereiden avulla:

Filtteri “Related Citations”: “Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.”

“Related citations”, tulos: 105 artikkelia. Jatkofiltrausta:• 4 +“Review” (julkaisuvuodet 2013,2011,2010, 1993)• 67 +DNA• 18 +“Ancient DNA”• 47 +DNA+Ancient• 31 +DNA+Ancient+free

Huom: filtteri “Humans” tai “other animals” ei ole järkevä, koskaNeanderthal ja Denisova menevät luokkaan “other animals”.

Marja Pirttivaara14.11.2014

Valitut artikkelit 1/4

1. Raghavan M et al: Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans. Nature. 2014 Jan 2;505(7481):87-91. doi: 10.1038/nature12736. Epub2013 Nov 20. PubMed PMID: 24256729.

2. Bollongino R et al: 2000 y of parallel societies in Stone Age Central Europe. Science. 2013 Oct 25;342(6157):479-81. doi: 10.1126/science.1245049. Epub 2013 Oct 10. PubMed PMID: 24114781.

3. Brandt G et al: Ancient DNA reveals key stages in the formation of central European mitochondrial genetic diversity. Science. 2013 Oct 11;342(6155):257-61. doi: 10.1126/science.1241844. PubMed PMID: 24115443.

4. Lazaridis et al: Ancient human genomes suggest three ancestral populations for present-day Europeans. Nature. 2014 Sep 18;513(7518):409-13. doi: 10.1038/nature13673. PubMed PMID: 25230663.

5. Petersen DC et al: Complex patterns of genomic admixture within Southern Africa. PLoS Genet. 2013;9(3):e1003309. doi: 10.1371/journal.pgen.1003309. Epub 2013 Mar 14. PubMed PMID: 23516368.

6. Cardoso S et al: The expanded mtDNA phylogeny of the Franco-Cantabrian region upholds the pre-Neolithic genetic substrate of Basques. PLoS One. 2013 Jul 3;8(7):e67835. doi: 10.1371/journal.pone.0067835. Print 2013. PubMed PMID: 23844106.

7. Fedorova SA et al: Autosomal and uniparental portraits of the native populations of Sakha (Yakutia): implications for the peopling of Northeast Eurasia. BMC Evol Biol. 2013 Jun 19;13:127. doi: 10.1186/1471-2148-13-127. PubMed PMID: 23782551.

14.11.2014 Marja Pirttivaara

Valitut artikkelit 2/48. Brotherton P et al: Neolithic mitochondrial haplogroup H genomes and the genetic origins of

Europeans. Nat Commun. 2013;4:1764. doi: 10.1038/ncomms2656. PubMed PMID: 23612305.

9. Der Sarkissian C et al: Ancient DNA reveals prehistoric gene-flow from Siberia in the complex human population history of North East Europe. PLoS Genet. 2013;9(2):e1003296. doi: 10.1371/journal.pgen.1003296. Epub 2013 Feb 14. PubMed PMID: 23459685.

10. Sánchez-Quinto F et al: Genomic affinities of two 7,000-year-old Iberian hunter-gatherers. Curr Biol. 2012 Aug 21;22(16):1494-9. doi: 10.1016/j.cub.2012.06.005. Epub 2012 Jun 28. PubMed PMID: 22748318.

11. Skoglund P et al: Origins and genetic legacy of Neolithic farmers and hunter-gatherers in Europe. Science. 2012 Apr 27;336(6080):466-9. doi: 10.1126/science.1216304. PubMed PMID: 22539720.

12. Henn BM et al: Genomic ancestry of North Africans supports back-to-Africa migrations. PLoS Genet. 2012 Jan;8(1):e1002397. doi: 10.1371/journal.pgen.1002397. Epub 2012 Jan 12. PubMed PMID: 22253600.

13. Hervella M et al: Ancient DNA from hunter-gatherer and farmer groups from Northern Spain supports a random dispersion model for the Neolithic expansion into Europe. PLoS One. 2012;7(4):e34417. doi: 10.1371/journal.pone.0034417. Epub 2012 Apr 25. Erratum in: PLoS One. 2012;7(7). doi:10.1371/annotation/3dac0b4f-f76e-4bc1-8559-acb41b87b02c. PubMed PMID:22563371.

14. Fu Q, Rudan P, Pääbo S, Krause J.: Complete mitochondrial genomes reveal Neolithic expansion into Europe. PLoS One. 2012;7(3):e32473. doi: 10.1371/journal.pone.0032473. Epub 2012 Mar 13. PubMed PMID: 22427842.

14.11.2014 Marja Pirttivaara

Valitut artikkelit 3/415. von Cramon-Taubadel N, Pinhasi R.: Craniometric data support a mosaic model of demic and

cultural Neolithic diffusion to outlying regions of Europe. Proc Biol Sci. 2011 Oct 7;278(1720):2874-80. doi: 10.1098/rspb.2010.2678. Epub 2011 Feb 23. PubMed PMID: 21345869.

16. Gignoux CR, Henn BM, Mountain JL.: Rapid, global demographic expansions after the origins of agriculture. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6044-9. doi: 10.1073/pnas.0914274108. Epub 2011 Mar 28. PubMed PMID: 21444824.

17. Batini C et al: Insights into the demographic history of African Pygmies from complete mitochondrial genomes. Mol Biol Evol. 2011 Feb;28(2):1099-110. doi: 10.1093/molbev/msq294. Epub 2010 Nov 1. PubMed PMID: 21041797.

18. Haak W et al: Ancient DNA from European early Neolithic farmers reveals their Near Eastern affinities. PLoS Biol. 2010 Nov 9;8(11):e1000536. doi: 10.1371/journal.pbio.1000536. PubMed PMID: 21085689.

19. Laval G, Patin E, Barreiro LB, Quintana-Murci L.: Formulating a historical and demographic model of recent human evolution based on resequencing data from noncoding regions. PLoS One. 2010 Apr 22;5(4):e10284. doi: 10.1371/journal.pone.0010284. PubMed PMID: 20421973.

20. Soares P et al: The archaeogenetics of Europe. Curr Biol. 2010 Feb 23;20(4):R174-83. doi: 10.1016/j.cub.2009.11.054. Review. PubMed PMID: 20178764.

21. Malmström H et al: Ancient DNA reveals lack of continuity between Neolithic hunter-gatherers and contemporary Scandinavians. Curr Biol. 2009 Nov 3;19(20):1758-62. doi: 10.1016/j.cub.2009.09.017. Epub 2009 Sep 24. PubMed PMID: 19781941.

14.11.2014 Marja Pirttivaara

Valitut artikkelit 4/422. Bramanti B et al: Genetic discontinuity between local hunter-gatherers and central Europe's first

farmers. Science. 2009 Oct 2;326(5949):137-40. doi: 10.1126/science.1176869. Epub 2009 Sep 3. PubMed PMID: 19729620.

23. Reich D et al: Reconstructing Indian population history. Nature. 2009 Sep 24;461(7263):489-94. doi: 10.1038/nature08365. PubMed PMID: 19779445.

24. Berniell-Lee G et al: Genetic and demographic implications of the Bantu expansion: insights from human paternal lineages. Mol Biol Evol. 2009 Jul;26(7):1581-9. doi: 10.1093/molbev/msp069. Epub 2009 Apr 15. PubMed PMID: 19369595.

25. Patin E et al: Inferring the demographic history of African farmers and pygmy hunter-gatherers using a multilocus resequencing data set. PLoS Genet. 2009 Apr;5(4):e1000448. doi: 10.1371/journal.pgen.1000448. Epub 2009 Apr 10. PubMed PMID: 19360089.

26. Ammerman AJ, Pinhasi R, Bánffy E.: Comment on "Ancient DNA from the first European farmers in 7500-year-old Neolithic sites". Science. 2006 Jun 30;312(5782):1875; author reply 1875. PubMed PMID: 16809513.

27. Haak W et al: Ancient DNA from the first European farmers in 7500-year-old Neolithic sites. Science. 2005 Nov 11;310(5750):1016-8. PubMed PMID: 16284177.

28. Brown MD et al: mtDNA haplogroup X: An ancient link between Europe/Western Asia and North America? Am J Hum Genet. 1998 Dec;63(6):1852-61. PubMed PMID: 9837837.

14.11.2014 Marja Pirttivaara

Mistä tunnistaa luotettavat muinaisDNA-analyysit?

• Julkaisutapa ja tekijät. Onko tieto julkaistu ja julkaisu käynyt läpi vertaisarvioinnin sekä julkaistu kansainvälisessä referoidussa julkaisusarjassa? PubMed on hyvä lähtökohta. http://www.ncbi.nlm.nih.gov/pubmed

• Näyte. Mistä näyte on peräisin, miten sitä on käsitelty ja säilytetty? Lupaava näyte on voitu pilata jo kaivauksilla.

• Laboratorio. Onko näyte analysoitu erillisessä laboratoriossa, joka on erikoistunut muinaisDNAhan?

• Työntekijät. Työntekijöillä tulee olla suojavaatteet ja työmenetelmien on oltava steriilit.

• Negatiiviset kontrollitestit. Samanaikaisesti muinaisDNA-näytteiden kanssa analysoidaan esim. puhdasta vettä, josta ei pitäisi löytyä mitään.

• Tulosten toistettavuus. Sekä omassa laboratoriossa että vieraassa laboratoriossa.

• Tulosten fylogeneettinen mielekkyys (haplopuu). Y-DNAn ja mitokondrioDNAn (mtDNA) mutaatiot liittävät tulokset isä- ja äitilinjoihin, joisas mutaatiot ovat tapahtuntee, ja sitä kautta haploryhmiin ja haplopuuhun. Kun tutkimus lähetetään referoitavaksi , referoijat vaativat tn tarkistuksen suhteessa haplopuuhunhttp://www.isogg.org/tree/

• Virhearvio (analyysi tulosten luotettavuudesta) on mukana ja selitettynä julkaisussa. Virhearvioistaan fyysikko tunnetaan - niin myös muinaisDNAn tutkijat….

Lisälukemista:

- Svante Pääbo: Neanderthal Man: In Search of Lost Genomes, Basic Books, 2014.http://www.theguardian.com/books/2014/feb/19/neanderthal-man-search-lost-genomes-svante-paabo

- Jennifer Raff: How to tell if an ancient DNA study is legitimate http://violentmetaphors.com/2014/02/07/how-to-tell-if-an-ancient-dna-study-is-legit/

- Lazaridis et al: Ancient human genomes suggest three ancestral populations for present-day Europeans. Nature. 2014 Sep 18;513(7518):409-13. Kontaminaatiota ja virheanalyysia on käsitelty poikkeuksellisen hyvin Supplementary information –osiossa (155 sivua, vapaasti saatavissa). http://www.nature.com/nature/journal/v513/n7518/extref/nature13673-s1.pdf

14.11.2014 Marja Pirttivaara

I Lazaridis et al. Nature 513, 409-413 (2014) doi:10.1038/nature13673

Lazaridis et al: Principal Component Analysis.

Fig. 2: PCA on all present-day west Eurasians, with ancient samples projected. European hunter-gatherers fall beyond present-day Europeans in the direction of European differentiation from the Near East. Stuttgart clusters with other Neolithic Europeans and present-day Sardinians. MA1 falls outside the variation of present-day west Eurasians in the direction of southern–northern differentiation along dimension 2.

Permission to use in this presentation from Copyright Clearance Center's RightsLink service www.copyright.com

14.11.2014 Marja Pirttivaara

I Lazaridis et al. Nature 513, 409-413 (2014) doi:10.1038/nature13673

Lazaridis et al: Modelling the relationship of European to non-European populations.

Fig. 3: A three-way mixture model that is a fit to the data for many populations. Present-day samples are coloured in blue, ancient in red, and reconstructed ancestral populations in green. Solid lines represent descent without mixture, and dashed lines represent admixture. We print mixture proportions and one standard error for the two mixtures relating the highly divergent ancestral populations. (We do not print the estimate for the ‘European’ population as it varies depending on the population.)

Permission to use in this presentation from Copyright Clearance Center's RightsLink service www.copyright.com 14.11.2014 Marja Pirttivaara

I Lazaridis et al. Nature 513, 409-413 (2014) doi:10.1038/nature13673

Fig. 7: Some north-eastern European populations (Chuvash, Finnish, Russian, Mordovian, Saami)

share more alleles with Han Chinese than with other Europeans who are arrayed in a cline from

Stuttgart to Lithuanians/Estonians in a plot of f4(Test, BedouinB; Han, Mbuti) against f4(Test,

BedouinB; MA1, Mbuti).

Permission to use in this presentation from Copyright Clearance Center's RightsLink service www.copyright.com

Lazaridis et al: Evidence for Siberian gene flow into far north-eastern Europe.

14.11.2014 Marja Pirttivaara

Petrous bones verus non-petrous bones

14.11.2014 Marja Pirttivaara

Percentage of non-clonal endogenous DNA recovered after shotgun sequencing. The sampled bone/tooth portion is circled in red. N.A. indicate that the library did not pass quality assessment for sequencing.

Gamba, C. et al: Genome flux and stasis in a five millennium transect of European prehistory. Nat. Commun. 5:5257 doi: 10.1038/ncomms6257 (2014). PubMed PMID 25334030

CC licence by Macmillan Publishers Ltd: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4218962/figure/f1/

MuinaisDNA-dataa – kaikkien saatavilla

14.11.2014 Marja Pirttivaara

Sample Name Sample Location Sex Y-DNA hg Mt-DNA hg Approx. Age byauthors

PubMed PMID GEDMatch**

Altai Neanderthal Denisova Cave, Siberia F 50,000 y http://www.eva.mpg.de/neandertal/index.html

F999902

Denisova Denisova Cave, Siberia F 30,000 y 22936568 F999903

Palaeo-Eskimo Greenland M Q1a D2a1 4,000 y 20148029 F999906

Mal’ta South-Central Siberia M R U 24,000 y 24256729 F999914

La Braña-Arintero León, Spain M C-V183 U5b2c1 7,000 y 24463515 F999915

LBK Stuttgart, Germany F T2c2 7,500 y 25230663 F999916

Motala-12 Östergötland, Sweden M I-L460 U2e1 7,000 y 25230663 F999917

Loschbour Loschbour, Luxembourg M I-L460 U5b1a 8,000 y 25230663 F999918

Clovis-Anzick-1 Montana, North America M Q-Z780 D4h3a 12,500 y 24522598 F999919

Hinxton-2 Cambridgshire, UK F H2a2b1 1300 y Sanger * F999921

Hinxton-3 Cambridgshire, UK F K1a4a1a2b 1300 y Sanger * F999922

Ajvide58 Sweden M I-CTS772 U4d 5000 y 24762536 F999924

Hinxton-4 Cambridgshire, UK M R-DF25 H1ag1 2000 y Sanger * F999925

Hinxton-5 Cambridgshire, UK F H2a2a1 1300 y Sanger * F999926

NE5 Kompolt-Kigyósér, Hungary M C-F3393 J1c 4990-5210 cal BC 25334030 F999927

NE7 Apc-Berekalja I., Hungary M I-L1228 N1a 4360-4490 cal BC 25334030 F999928

IR1 Ludas-Varjú-dűlő, Hungary M N-M231 G2a1 830-980 cal BC 25334030 F999929

CO1 Apc-Berekalja I., Hungary F H 2700-2900 cal BC 25334030 F999930

KO1 Tiszaszőlős-Domaháza, Hungary M I-L68 R3 5650-5780 cal BC 25334030 F999931

NE6 Apc-Berekalja I., Hungary M C-P255 K1a3a3 4950-5300 cal BC 25334030 F999932

BR2 Ludas-Varjú-dűlő, Hungary M J-M67 K1a1a 1110-1270 cal BC 25334030 F999933

Gökhem2 Sweden F H1c 5000 y 24762536 F999934

Ust'-Ishim Ust'-Ishim, Siberia M K-M526 R 45,000 y 25341783 F999935

Kostenki14 European Russia M C-V199 U2b 38,700-36,200 y 25378462 F999936

NE1 Polgár-Ferenci-hát, Hungary F U5b2c 5070-5310 cal BC 25334030?

Tyrolean Iceman(ERP001144)

Tisenjoch Pass, Oetztal Alps M 5300 y http://www.ebi.ac.uk/ena/data/view/ERP001144

http://www.y-str.org/p/ancient-dna.html * http://sra.dnanexus.com/studies/ERP003900 ** http://www.gedmatch.com

MuinaisDNA-haploryhmätuloksia: Y-DNA ja mtDNA

Y-DNA Y-DNA

C-F3393 I-L460

CF-M3690 I-L68

C-P255 I-M258

C-V183 I-PF3796

C-V199 J-M67

F-M235 K-M526

F-P139 N-M231

HIJK-F929 Q1a

I-CTS4077 Q-Z780

I-CTS6343 R

I-CTS772 R1?

I-L1228 R-DF25

I-L460 R-L151

14.11.2014 Marja Pirttivaara

mtDNA mtDNA mtDNA

B2 J1c U

B4b'd'e K1 U2b

D1 K1a1a U2e1

D2a1 K1a1b1b U2e1'2'3

D4h3a K1a3a3 U3b

G2a1 K1a4a1a2b U4d

H K1c1 U5a1

H1ag1 K1e U5a1f1a

H1c L3 U5a2 orU5a1f1a1

H1c9a N1a U5a2d

H2a2a1 O1a U5b1a

H2a2b1 R U5b2c

HV R3 U5b2c1

HV0a T2c2 U5e1

X2bhttp://www.y-str.org/p/ancient-dna.htm

Y-DNA Mieslinjojen migraatiokartta

© Gene by Gene, lupa14.11.2014 Marja Pirttivaara

mtDNA migraatiokartta

© Gene by Gene, lupa6.11.2014 Marja Pirttivaara

Lisätietoja

Hyvä lisätieto- ja linkkikokoelma:

http://www.isogg.org/wiki/Ancient_DNA

Snippitietoa: http://www.snpedia.com

Suosittelen: genomiikan ja bioinformatiikan

online-peruskurssit itseopiskeluun:Introduction to Genomics

Introduction to Bioinformatics

http://www.genomicseducation.hee.nhs.uk

14.11.2014 Marja Pirttivaara

Kiitos!

marja.pirttivaara (@) gmail.comTwitter: Marja_P

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