Mapping gene flow between ancient hominins through demography-aware inference of the ancestral recombination graph


Autoři: Melissa J. Hubisz aff001;  Amy L. Williams aff001;  Adam Siepel aff002
Působiště autorů: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, United States of America aff001;  Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America aff002
Vyšlo v časopise: Mapping gene flow between ancient hominins through demography-aware inference of the ancestral recombination graph. PLoS Genet 16(8): e32767. doi:10.1371/journal.pgen.1008895
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008895

Souhrn

The sequencing of Neanderthal and Denisovan genomes has yielded many new insights about interbreeding events between extinct hominins and the ancestors of modern humans. While much attention has been paid to the relatively recent gene flow from Neanderthals and Denisovans into modern humans, other instances of introgression leave more subtle genomic evidence and have received less attention. Here, we present a major extension of the ARGweaver algorithm, called ARGweaver-D, which can infer local genetic relationships under a user-defined demographic model that includes population splits and migration events. This Bayesian algorithm probabilistically samples ancestral recombination graphs (ARGs) that specify not only tree topologies and branch lengths along the genome, but also indicate migrant lineages. The sampled ARGs can therefore be parsed to produce probabilities of introgression along the genome. We show that this method is well powered to detect the archaic migration into modern humans, even with only a few samples. We then show that the method can also detect introgressed regions stemming from older migration events, or from unsampled populations. We apply it to human, Neanderthal, and Denisovan genomes, looking for signatures of older proposed migration events, including ancient humans into Neanderthal, and unknown archaic hominins into Denisovans. We identify 3% of the Neanderthal genome that is putatively introgressed from ancient humans, and estimate that the gene flow occurred between 200-300kya. We find no convincing evidence that negative selection acted against these regions. Finally, we predict that 1% of the Denisovan genome was introgressed from an unsequenced, but highly diverged, archaic hominin ancestor. About 15% of these “super-archaic” regions—comprising at least about 4Mb—were, in turn, introgressed into modern humans and continue to exist in the genomes of people alive today.

Klíčová slova:

Gene flow – Hominins – Introgression – Neanderthals – Paleoanthropology – Paleogenetics – Simulation and modeling – X chromosomes


Zdroje

1. Green RE, Krause J, Briggs AW, Maricic T, Stenzel U, Kircher M, et al. A draft sequence of the Neandertal genome. Science. 2010;328(5979):710–722. doi: 10.1126/science.1188021 20448178

2. Prüfer K, Racimo F, Patterson N, Jay F, Sankararaman S, Sawyer S, et al. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature. 2014;505(7481):43–49. doi: 10.1038/nature12886 24352235

3. Sankararaman S, Mallick S, Dannemann M, Prüfer K, Kelso J, Pääbo S, et al. The genomic landscape of Neanderthal ancestry in present-day humans. Nature. 2014;507:354–357. doi: 10.1038/nature12961 24476815

4. Meyer M, Kircher M, Gansauge MT, Li H, Racimo F, Mallick S, et al. A high-coverage genome sequence from an archaic Denisovan individual. Science. 2012;338(6104):222–226. doi: 10.1126/science.1224344 22936568

5. Mendez FL, Watkins JC, Hammer MF. Global Genetic Variation at OAS1 Provides Evidence of Archaic Admixture in Melanesian Populations. Molecular Biology and Evolution. 2012;29(6):1513–1520. doi: 10.1093/molbev/msr301

6. Sankararaman S, Mallick S, Patterson N, Reich D. The combined landscape of Denisovan and Neanderthal ancestry in present-day humans. Current Biology. 2016;26:1241–1247. doi: 10.1016/j.cub.2016.03.037

7. Slon V, Mafessoni F, Vernot B, de Filippo C, Grote S, Viola B, et al. The genome of the offspring of a Neanderthal mother and a Denisovan father. Nature. 2018;561(7721):113–116. doi: 10.1038/s41586-018-0455-x 30135579

8. Kuhlwilm M, Gronau I, Hubisz MJ, de Filippo C, Prado-Martinez J, Kircher M, et al. Ancient gene flow from early modern humans into Eastern Neanderthals. Nature. 2016;530(7591):429–433. doi: 10.1038/nature16544 26886800

9. Prüfer K, de Filippo C, Grote S, Mafessoni F, Korlević P, Hajdinjak M, et al. A high-coverage Neandertal genome from Vindija Cave in Croatia. Science. 2017;358(6363):655–658. doi: 10.1126/science.aao1887 28982794

10. Hammer MF, Woerner AE, Mendez FL, Watkins JC, Wall JD. Genetic evidence for archaic admixture in Africa. Proceedings of the National Academy of Sciences. 2011;108(37):15123–15128.

11. Hsieh P, Woerner AE, Wall JD, Lachance J, Tishkoff SA, Gutenkunst RN, et al. Model-based analyses of whole-genome data reveal a complex evolutionary history involving archaic introgression in Central African Pygmies. Genome Research. 2016;26(3):291–300. doi: 10.1101/gr.196634.115 26888264

12. Ragsdale AP, Gravel S. Models of archaic admixture and recent history from two-locus statistics. PLOS Genetics. 2019;15(6):1–19.

13. Petr M, Pääbo S, Kelso J, Vernot B. Limits of long-term selection against Neandertal introgression. Proceedings of the National Academy of Sciences. 2019;116(5):1639–1644.

14. Gronau I, Hubisz MJ, Gulko B, Danko CG, Siepel A. Bayesian inference of ancient human demography from individual genome sequences. Nat Genet. 2011;43(10):1031–1034. doi: 10.1038/ng.937

15. Plagnol V, Wall JD. Possible ancestral structure in human populations. PLOS Genetics. 2006;2(7):1–8.

16. Vernot B, Akey JM. Resurrecting surviving Neandertal lineages from modern human genomes. Science. 2014;343(6174):1017–1021. doi: 10.1126/science.1245938

17. Browning SR, Browning BL, Zhou Y, Tucci S, Akey JM. Analysis of human sequence data reveals two pulses of archaic Denisovan admixture. Cell. 2018;173(1):53–61.e9. doi: 10.1016/j.cell.2018.02.031

18. Hudson RR. Gene genealogies and the coalescent process. Oxford surveys in evolutionary biology. 1990;7(1):44.

19. Griffiths RC, Marjoram P. Ancestral Inference from Samples of DNA Sequences with Recombination. Journal of Computational Biology. 1996;3(4):479–502. doi: 10.1089/cmb.1996.3.479

20. Griffiths R, Marjoram P. An ancestral recombination graph. In: Donnelly P, Tavaré S, editors. Progress in Population Genetics and Human Evolution. Springer Verlag; 1997. p. 257–270.

21. Rasmussen MD, Hubisz MJ, Gronau I, Siepel A. Genome-wide inference of ancestral recombination graphs. PLoS Genet. 2014;10(5):e1004342. doi: 10.1371/journal.pgen.1004342

22. Gutenkunst RN, Hernandez RD, Williamson SH, Bustamante CD. Inferring the joint demographic history of multiple populations from multidimensional SNP frequency data. PLoS Genet. 2009;5(10):e1000695. doi: 10.1371/journal.pgen.1000695

23. Reich D, Green RE, Kircher M, Krause J, Patterson N, Durand EY, et al. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature. 2010;468:1053 EP –. doi: 10.1038/nature09710 21179161

24. Mallick S, Li H, Lipson M, Mathieson I, Gymrek M, Racimo F, et al. The Simons Genome Diversity Project: 300 genomes from 142 diverse populations. Nature. 2016;538:201–206. doi: 10.1038/nature18964 27654912

25. Raney BJ, Dreszer TR, Barber GP, Clawson H, Fujita PA, Wang T, et al. Track data hubs enable visualization of user-defined genome-wide annotations on the UCSC Genome Browser. Bioinformatics. 2013;30(7):1003–1005. doi: 10.1093/bioinformatics/btt637 24227676

26. Lai CSL, Fisher SE, Hurst JA, Vargha-Khadem F, Monaco AP. A forkhead-domain gene is mutated in a severe speech and language disorder. Nature. 2001;413(6855):519–523. doi: 10.1038/35097076

27. Konopka G, Bomar JM, Winden K, Coppola G, Jonsson ZO, Gao F, et al. Human-specific transcriptional regulation of CNS development genes by FOXP2. Nature. 2009;462:213 EP –. doi: 10.1038/nature08549 19907493

28. Steinrücken M, Spence JP, Kamm JA, Wieczorek E, Song YS. Model-based detection and analysis of introgressed Neanderthal ancestry in modern humans. Molecular Ecology. 2018;27(19):3873–3888. doi: 10.1111/mec.14565

29. Kelleher J, Wong Y, Wohns AW, Fadil C, Albers PK, McVean G. Inferring whole-genome histories in large population datasets. Nat Genet. 2019;51(9):1330–1338. doi: 10.1038/s41588-019-0483-y

30. Speidel L, Forest M, Shi S, Myers SR. A method for genome-wide genealogy estimation for thousands of samples. Nat Genet. 2019;51(9):1321–1329. doi: 10.1038/s41588-019-0484-x

31. Meyer M, Arsuaga JL, de Filippo C, Nagel S, Aximu-Petri A, Nickel B, et al. Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins. Nature. 2016;531:504 EP –. doi: 10.1038/nature17405 26976447

32. Posth C, Wißing C, Kitagawa K, Pagani L, van Holstein L, Racimo F, et al. Deeply divergent archaic mitochondrial genome provides lower time boundary for African gene flow into Neanderthals. Nature Communications. 2017;8:16046 EP –. doi: 10.1038/ncomms16046 28675384

33. Hershkovitz I, Weber GW, Quam R, Duval M, Grün R, Kinsley L, et al. The earliest modern humans outside Africa. Science. 2018;359(6374):456–459. doi: 10.1126/science.aap8369 29371468

34. Harvati K, Röding C, Bosman AM, Karakostis FA, Grün R, Stringer C, et al. Apidima Cave fossils provide earliest evidence of Homo sapiens in Eurasia. Nature. 2019;571(7766):500–504. doi: 10.1038/s41586-019-1376-z 31292546

35. Jacobs GS, Hudjashov G, Saag L, Kusuma P, Darusallam CC, Lawson DJ, et al. Multiple deeply divergent Denisovan ancestries in Papuans. Cell. 2019;177(4):1010–1021.e32. doi: 10.1016/j.cell.2019.02.035 30981557

36. Durvasula A, Sankararaman S. Recovering signals of ghost archaic introgression in African populations. bioRxiv. 2019;

37. Fenner JN. Cross-cultural estimation of the human generation interval for use in genetics-based population divergence studies. American Journal of Physical Anthropology. 2005;128(2):415–423. doi: 10.1002/ajpa.20188

38. Kelleher J, Etheridge AM, McVean G. Efficient coalescent simulation and genealogical analysis for large sample sizes. PLoS Comput Biol. 2016;12(5):1–22.

39. Li H, Durbin R. Inference of human population history from individual whole-genome sequences. Nature. 2011;475:493–496. doi: 10.1038/nature10231

40. Hinch AG, Tandon A, Patterson N, Song Y, Rohland N, Palmer CD, et al. The landscape of recombination in African Americans. Nature. 2011;476(7359):170–175. doi: 10.1038/nature10336 21775986


Článek vyšel v časopise

PLOS Genetics


2020 Číslo 8

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

VIRTUÁLNÍ ČEKÁRNA ČR Jste praktický lékař nebo pediatr? Zapojte se! Jste praktik nebo pediatr? Zapojte se!

×