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Autosomes & Agamemnon's Face
- 1. 2015 Family Tree DNA Conference Houston, Texas Razib Khan Autosomes & Agamemnon's face
- 2. The age of the whole genome
- 3. Revolutionary science l First human genome cost $3,000,000,000 l My son was sequenced in 2014 in utero for $500 (7x coverage) l You can get a retail 30x (highly quality) genome today for $1,850 today l We now have hundreds of ancient genomes of humans of various qualities! l Half the American population will have high quality WGS by 2025
- 4. Three stages of -omics l Science as industrial process (then) l Science as a laboratory process (now) l Science as a consumer good (soon)
- 5. What is in the world-wide genome? l 3 billion base pairs (~3 GB) l >80 million SNPs l 4 million indels l ~60K structural variants 1000 Genomes Consortium
- 6. What is in your genome? l 3 billion base pairs (~3 GB) l ~4 million SNPs l ~15 million singletons l ~500K indels 1000 Genomes Consortium
- 7. Why is your genome important? l You are not your genome l But who you are begins with your genome l A genome is not sufficient to make you, but it is necessary
- 8. So why are we focusing on SNPs not WGS? l WGS is expensive l It takes longer (more resources) l Most of it is not informative l We can't interpret a lot of the variation (e.g., copy number variation) l More data takes longer to analyze, even on powerful computers
- 9. What's in your SNPs? l SNP chip assays survey ~10K to 1 million markers l Human chips generally 500K to 1 million markers l Only a minority of human SNPs are captured on a given chip l Many of the markers are intergenic (not among ~20K genes), while the genic ones may not be functional
- 10. A few SNPs go a long way l 30 “ancestrally informative markers” give you enough information to tell inter- continental differences (e.g., African vs. European) l 1,000 random SNPs are sufficient for data heavy population assignment at this scale l 10,000 random SNPs get you most of the way to intra-continental differences (e.g., China vs. Japan) l >100,000 markers lots of power
- 11. Just a matter of power
- 13. An embarrassment of marker riches! We have the technology, we can cover the genome!
- 14. So how we do get this?
- 15. A problem of perception l Y and mtDNA lineages are passed on as a single unit l The autosomal genome is a synthesis of billions of co-inherited blocks with l Visualizations of relatedness on the autosomal genome have to simplify and reduce numerous distinct genealogies l Today the difficulty is representing the variation, rather than getting it
- 16. Pedigrees are intuitive, but they mask genomic complexity
- 18. But exceptions make a tidy story difficult!
- 19. Autosomal ancestry inference as Reader's Digest of your genomic history 1)Take thousands of characters 2)Put them into the scaffold of a predetermined plot 3)Reduce down to fewer than fifty narrative threads
- 20. Sometimes the “composition” might turn out a little confusing, but we hope it tastes good 1)Take ingredients, 300K SNPs across thousands of individuals 2)Create a model 3)Check the parameters across the individuals which are the best fit to the model
- 21. Or, made more “sciencey” 1. Take data (e.g., genetic variation) 2. Take a model (e.g., Hardy- Weinberg) 3. Plug in values (e.g., 2 populations, 3 populations, 4 populations….) 4. Produce plots!
- 22. MyOrigins version 2.0, 24 clusters, +6 from 1.0 Ashkenazi Balkan East Africa Finland Germany British Italy Mbuti Pygmies North African North Amerindian North India North West Asia Northeast Asia Papuan Slavic South Amerindian South India South West Asia Sardinian Southeast Asia Siberian Spain Scandinavian West Africa
- 23. Better Native American clusters l North Amerindian uses Pima Indians + ftDNA data set l Has more Na Dene signal l South Amerindian uses Amazonian Indians l Has an “Austro- Melanesian” signature at low levels l Using this as a “reference” for all Amerindians was a mistake!
- 24. A Siberian cluster l Very few customers are going to be much Siberian l But Siberians turn out to be very important in the history of Eurasia and the New World l Many Native Americans will pick up some of this signature...and Europeans
- 25. A Sardinian cluster l Very few customers are going to be much Sardinian l But Sardinians turn out to be very important in the history of Europe l If you have Sardinian admixture (many South Europeans will) it will tell you about deep roots
- 26. New Southern European Clusters l The Italian cluster is biased toward South Italian samples l There has been a fair amount of gene flow in Southern Europe, but a definite “cline” from Spain to Italy l Many Iberians will have “Italian” and vice versa l The Balkan cluster defines the eastern position of the Southern European “cline” l It is a composite of indigenous groups overlain with Slavic migration within the last ~1,500 years
- 27. The FtDNA database is big!
- 28. Myth made real: Agamemnon's face!
- 29. Coke & Pepsi of ancient DNA David Reich & Eske Willerslev
- 30. Phylogenomics vs population genomics Coop et al. & Cavalli-Sforza et al.
- 31. Standing on the shoulders of two papers l Eight thousand years of natural selection in Europe, Mathieson et al. l Population genomics of Bronze Age Eurasia, Allentoft et al.
- 32. Of Gods and Men l ““There were giants in the earth in those days; and also after that, when the sons of God came in unto the daughters of men, and they bare children to them, the same became mighty men which were of old, men of renown.””
- 33. Dream-Time come to life
- 34. The “Others” l Tuatha Dé Danann l Pelasgians l Elves l Dwarves l Trolls l Fairies l The Grendel
- 35. Collective memory or fiction? l Oral memory degrades l Humans tend to create the same fictive narratives l Legends and myths have low fidelity with the reality of the past l Memonic techniques were much more advanced in the past l The structure of narrative and its utility can maintain its fidelity
- 36. Ancient Europe was inhabited by very different people l Hunters and gatherers, the oldest ones l The first farmers l And the horse people l The genetic distance between some of these groups was comparable to that between Chinese and modern North Europeans
- 37. Foreign faces Carles Lalueza-Fox, Institute of Evolutionary Biology (CSIC-UPF)
- 38. The gene that makes you “white”, SLC24A5
- 39. It is not indigenous to Europe ● It is entirely absent in Mesolithic Western Europeans, that is, the oldest group ● It is present at very high frequencies in both the horse people and the farmers
- 40. SLC45A2 makes you “white” too!
- 41. It was not common in ancient Europe ● Again, absent in Mesolithic Western Europeans ● Present in moderately low frequencies among farmers and at moderately high frequencies among the horse people
- 42. KITLG makes you blonde
- 43. HERC2-OCA2 makes you blue eyed
- 44. It was very common in ancient Europe ● All of the old hunters and gatherers had the blue eye variety ● The horse people and the farmers did not have that variant
- 45. Alleles across time Allentoft et al.
- 46. Alleles across time part 2 Mathieson et al.
- 47. Northern Europeans are new thing ● The genetic architecture responsible for the distinctive Northern European phenotype is very new ● It almost certainly post-dates the Old Kingdom of Egypt ● In other words, this is selection and evolution occurring during historical periods!
- 48. A genetic architecture similar to Copper Age Europeans ● SLC24A5, fixed “European” variant ● SLC45A2, heterozygote ● OCA2/HERC2, heterozygote ● KITLG, heterozygote
- 49. Mathieson et al. Giants from the steppe? One Krasnodar sample was 6'11!
- 50. Milk does a genome good?
- 51. The oldest “Swedes” looked unique ● Unlike Western hunters and gatherers a group from Motala in Sweden seem to have many lighter color alleles (though still darker than modern Northern Europeans) ● But, they happen to carry a genetic variant that is very rare in Europe today, that is associated with East Asians and aspects of their phenotype such as very thick and straight hair ● Motala hunters and gatherers have this gene in frequencies common in Southern Chinese
- 52. Behind the mask of myth ● We now know that Europeans on the edge of history consisted of very distinct peoples ● Additionally, the genetic traits we are aware of suggest they looked very different from each other, and from one another Europeans ● And, we now have evidence in other societies of folk legends rooted in fact persisting for thousands of years
- 53. More than metaphor The myths and legends of the people of Europe, and other regions, may harbor very important and illuminating anthropological and historical information. Stay tuned!
- 54. R1a addendum: ● Yamna R1b ● Srubna R1a ● Turnover on the steppe!