Harnessing ancient genomes to study the history of human adaptation

KEY POINTS * Ancient DNA provides transformative insight into the history of human adaptation via the ability to directly track genetic variant frequency changes across space and time. *

Analyses of human, archaic hominin, and domesticated plant and animal ancient genomic data sets can each inform our understanding of past human evolution and behaviour. * The number of

published ancient genomic data sets is growing substantially each year, contributing expanded precision and power to evolutionary analyses based on these data. * Human ancient genome data

have already helped characterize the histories of biological adaptations to northern latitudes and cold climates, agriculture-associated dietary shifts, and a changing infectious disease

landscape. * After migrating out of Africa, ancient human populations acquired genetic variants conferring fitness advantages in Eurasian environments through adaptive introgression with

archaic hominin populations who had already been inhabiting this region for hundreds of thousands of years. * Ancient genome data reveal some substantial time lags between documented

environmental or cultural changes and the appearance and spread of genetic variants associated with human biological adaptations, with possible implications for intervening human health

and/or potential compensatory cultural behaviours. ABSTRACT The past several years have witnessed an explosion of successful ancient human genome-sequencing projects, with genomic-scale

ancient DNA data sets now available for more than 1,100 ancient human and archaic hominin (for example, Neandertal) individuals. Recent 'evolution in action' analyses have started

using these data sets to identify and track the spatiotemporal trajectories of genetic variants associated with human adaptations to novel and changing environments, agricultural lifestyles,

and introduced or co-evolving pathogens. Together with evidence of adaptive introgression of genetic variants from archaic hominins to humans and emerging ancient genome data sets for

domesticated animals and plants, these studies provide novel insights into human evolution and the evolutionary consequences of human behaviour that go well beyond those that can be obtained

from modern genomic data or the fossil and archaeological records alone. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

institution ACCESS OPTIONS Access through your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription $32.99 / 30 days cancel

any time Learn more Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink *

Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional

subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS ANCIENT GENOMES IN SOUTH PATAGONIA REVEAL POPULATION MOVEMENTS ASSOCIATED WITH TECHNOLOGICAL

SHIFTS AND GEOGRAPHY Article Open access 03 August 2020 HIGH-RESOLUTION GENOMIC HISTORY OF EARLY MEDIEVAL EUROPE Article Open access 01 January 2025 PEOPLING OF THE AMERICAS AS INFERRED FROM

ANCIENT GENOMICS Article 16 June 2021 REFERENCES * Huxley, T. H. _Evidence as to Man's Place in Nature_ (Williams and Norgate, 1863). Google Scholar  * Darwin, C. _The Descent of Man,

and Selection in Relation to Sex_ (John Murray, 1871). Book  Google Scholar  * Fan, S., Hansen, M. E. B., Lo, Y. & Tishkoff, S. A. Going global by adapting local: A review of recent

human adaptation. _Science_ 354, 54–59 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Laland, K. N., Odling-Smee, J. & Myles, S. How culture shaped the human genome:

bringing genetics and the human sciences together. _Nat. Rev. Genet._ 11, 137–148 (2010). Article  CAS  PubMed  Google Scholar  * Scheinfeldt, L. B. & Tishkoff, S. A. Recent human

adaptation: genomic approaches, interpretation and insights. _Nat. Rev. Genet._ 14, 692–702 (2013). Article  PubMed  PubMed Central  Google Scholar  * Sabeti, P. C. et al. Positive natural

selection in the human lineage. _Science_ 312, 1614–1620 (2006). Article  CAS  PubMed  Google Scholar  * Raj, T. et al. Common risk alleles for inflammatory diseases are targets of recent

positive selection. _Am. J. Hum. Genet._ 92, 517–529 (2013). Article  CAS  PubMed  PubMed Central  Google Scholar  * Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L. & Denko, N. C.

HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. _Cell Metab._ 3, 187–197 (2006). Article  CAS  PubMed  Google Scholar  * Natarajan, V. T.

et al. IFN-γ signaling maintains skin pigmentation homeostasis through regulation of melanosome maturation. _Proc. Natl Acad. Sci. USA_ 111, 2301–2306 (2014). Article  CAS  PubMed  PubMed

Central  Google Scholar  * Norton, H. L. et al. Genetic evidence for the convergent evolution of light skin in Europeans and East Asians. _Mol. Biol. Evol._ 24, 710–722 (2006). Article  CAS

  PubMed  Google Scholar  * Pickrell, J. K. & Reich, D. Toward a new history and geography of human genes informed by ancient DNA. _Trends Genet._ 30, 377–389 (2014). Article  CAS 

PubMed  PubMed Central  Google Scholar  * Nielsen, R. et al. Tracing the peopling of the world through genomics. _Nature_ 541, 302–310 (2017). Article  CAS  PubMed  PubMed Central  Google

Scholar  * Orlando, L., Gilbert, M. T. P. & Willerslev, E. Reconstructing ancient genomes and epigenomes. _Nat. Rev. Genet._ 16, 395–408 (2015). Article  CAS  PubMed  Google Scholar  *

Llamas, B., Willerslev, E. & Orlando, L. Human evolution: a tale from ancient genomes. _Phil. Trans. R. Soc. B_ 372, 20150484 (2016). Article  CAS  Google Scholar  * Nakagome, S. et al.

Estimating the ages of selection signals from different epochs in human history. _Mol. Biol. Evol._ 33, 657–669 (2016). Article  CAS  PubMed  Google Scholar  * Field, Y. et al. Detection of

human adaptation during the past 2000 years. _Science_ 354, 760–764 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Malaspinas, A.-S., Malaspinas, O., Evans, S. N. &

Slatkin, M. Estimating allele age and selection coefficient from time-serial data. _Genetics_ 192, 599–607 (2012). Article  PubMed  PubMed Central  Google Scholar  * Sams, A. J., Hawks, J.

& Keinan, A. The utility of ancient human DNA for improving allele age estimates, with implications for demographic models and tests of natural selection. _J. Hum. Evol._ 79, 64–72

(2015). Article  PubMed  Google Scholar  * Gamba, C. et al. Genome flux and stasis in a five millennium transect of European prehistory. _Nat. Commun._ 5, 5257 (2014). Article  CAS  PubMed 

Google Scholar  * Mathieson, I. et al. Genome-wide patterns of selection in 230 ancient Eurasians. _Nature_ 528, 499–503 (2015). THIS PAPER PERFORMED A GENOME-WIDE SCAN FOR SIGNATURES OF

POSITIVE SELECTION WITH ANCIENT GENOME DATA FROM 230 EUROPEANS (!8,500–2,300 YEARS BP ) AND CHARACTERIZED THE SPATIOTEMPORAL FREQUENCY TRAJECTORIES OF ADAPTIVE ALLELES RELATED TO DIET, SKIN

PIGMENTATION, STATURE AND THE IMMUNE RESPONSE. Article  CAS  PubMed  PubMed Central  Google Scholar  * Gelabert, P., Olalde, I., de-Dios, T., Civit, S. & Lalueza-Fox, C. Malaria was a

weak selective force in ancient Europeans. _Sci. Rep._ 7, 1377 (2017). Article  PubMed  PubMed Central  CAS  Google Scholar  * Buckley, M. T. et al. Selection in Europeans on fatty acid

desaturases associated with dietary changes. _Mol. Biol. Evol._ 34, 1307–1318 (2017). Article  CAS  PubMed  PubMed Central  Google Scholar  * Ye, K., Gao, F., Wang, D., Bar-Yosef, O. &

Keinan, A. Dietary adaptation of _FADS_ genes in Europe varied across time and geography. _Nat. Ecol. Evol._ 1, 0167 (2017). Article  Google Scholar  * Sverrisdóttir, O. Ó. et al. Direct

estimates of natural selection in Iberia indicate calcium absorption was not the only driver of lactase persistence in Europe. _Mol. Biol. Evol._ 31, 975–983 (2014). Article  CAS  PubMed 

Google Scholar  * Günther, T. et al. Genomics of Mesolithic Scandinavia reveal colonization routes and high-latitude adaptation. Preprint at _bioRxiv_ http://dx.doi.org/10.1101/164400

(2017). THIS STUDY CONDUCTED A GENOME-WIDE SCAN OF POSITIVE SELECTION USING ANCIENT GENOME DATA FROM SEVEN SCANDINAVIAN INDIVIDUALS (!9,500–6,000 YEARS BP ) TO REVEAL A HAPLOTYPE THAT THE

AUTHORS PROPOSE MAY UNDERLIE PHYSIOLOGICAL ADAPTATION TO COLD CLIMATE. * Stephan, W. Signatures of positive selection: from selective sweeps at individual loci to subtle allele frequency

changes in polygenic adaptation. _Mol. Ecol._ 25, 79–88 (2016). Article  CAS  PubMed  Google Scholar  * Allentoft, M. E. et al. Population genomics of Bronze Age Eurasia. _Nature_ 522,

167–172 (2015). Article  CAS  PubMed  Google Scholar  * Haak, W. et al. Massive migration from the steppe was a source for Indo–European languages in Europe. _Nature_ 522, 207–211 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar  * Olalde, I. et al. The Beaker phenomenon and the genomic transformation of northwest Europe. Preprint at _bioRxiv_

http://dx.doi.org/10.1101/135962 (2017). * Cassidy, L. M. et al. Neolithic and Bronze Age migration to Ireland and establishment of the insular Atlantic genome. _Proc. Natl Acad. Sci. USA_

113, 368–373 (2016). Article  CAS  PubMed  Google Scholar  * Shennan, S. Evolutionary demography and the population history of the European early Neolithic. _Hum. Biol._ 81, 339–355 (2009).

Article  PubMed  Google Scholar  * Leonardi, M. et al. Evolutionary patterns and processes: lessons from ancient DNA. _Syst. Biol._ 66, e1–e29 (2017). PubMed  Google Scholar  * Mirazón Lahr,

M. The shaping of human diversity: filters, boundaries and transitions. _Phil. Trans. R. Soc. B_ 371, http://dx.doi.org/10.1098/rstb.2015.0241 (2016). * Stewart, J. R. & Stringer, C. B.

Human evolution out of Africa: the role of refugia and climate change. _Science_ 335, 1317–1321 (2012). Article  CAS  PubMed  Google Scholar  * Richards, M. A brief review of the

archaeological evidence for Palaeolithic and Neolithic subsistence. _Eur. J. Clin. Nutr._ 56, 1262–1278 (2002). Article  Google Scholar  * Perry, G. H. Parasites and human evolution. _Evol.

Anthropol._ 23, 218–228 (2014). Article  PubMed  Google Scholar  * Pearce-Duvet, J. M. C. The origin of human pathogens: evaluating the role of agriculture and domestic animals in the

evolution of human disease. _Biol. Rev._ 81, 369–382 (2006). Article  PubMed  Google Scholar  * Jablonski, N. G. & Chaplin, G. Human skin pigmentation as an adaptation to UV radiation.

_Proc. Natl Acad. Sci. USA_ 107, 8962–8968 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Chaplin, G. & Jablonski, N. G. Vitamin D and the evolution of human

depigmentation. _Am. J. Phys. Anthropol._ 139, 451–461 (2009). Article  PubMed  Google Scholar  * Brickley, M. B. et al. Ancient vitamin D deficiency: long-term trends. _Curr. Anthropol._

58, 420–427 (2017). Article  Google Scholar  * Ovesen, L., Brot, C. & Jakobsen, J. Food contents and biological activity of 25-hydroxyvitamin D: a vitamin D metabolite to be reckoned

with? _Ann. Nutr. Metab._ 47, 107–113 (2003). Article  CAS  PubMed  Google Scholar  * Bodnar, L. M. et al. Maternal vitamin D deficiency increases the risk of preeclampsia. _J. Clin.

Endocrinol. Metab._ 92, 3517–3522 (2007). Article  CAS  PubMed  Google Scholar  * Wang, T. J. et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study.

_Lancet_ 376, 180–188 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Lao, O., de Gruijter, J. M., van Duijn, K., Navarro, A. & Kayser, M. Signatures of positive

selection in genes associated with human skin pigmentation as revealed from analyses of single nucleotide polymorphisms. _Ann. Hum. Genet._ 71, 354–369 (2007). Article  CAS  PubMed  Google

Scholar  * Sturm, R. A. et al. Human pigmentation genes under environmental selection. _Genome Biol._ 13, 248–263 (2012). Article  CAS  PubMed  PubMed Central  Google Scholar  * Beleza, S.

et al. The timing of pigmentation lightening in Europeans. _Mol. Biol. Evol._ 30, 24–35 (2013). Article  CAS  PubMed  Google Scholar  * Günther, T. et al. Ancient genomes link early farmers

from Atapuerca in Spain to modern-day Basques. _Proc. Natl Acad. Sci. USA_ 112, 11917–11922 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * González-Fortes, G. et al.

Paleogenomic evidence for multi-generational mixing between Neolithic farmers and Mesolithic hunter–gatherers in the Lower Danube Basin. _Curr. Biol._ 27, 1801–1810.e10 (2017). Article 

PubMed  PubMed Central  CAS  Google Scholar  * Jones, E. R. et al. Upper Palaeolithic genomes reveal deep roots of modern Eurasians. _Nat. Commun._ 6, 8912 (2015). Article  CAS  PubMed 

Google Scholar  * Broushaki, F. et al. Early Neolithic genomes from the eastern Fertile Crescent. _Science_ 353, 499–503 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  *

Olalde, I. et al. Derived immune and ancestral pigmentation alleles in a 7,000-year-old Mesolithic European. _Nature_ 507, 225–228 (2014). Article  CAS  PubMed  PubMed Central  Google

Scholar  * Lazaridis, I. et al. Ancient human genomes suggest three ancestral populations for present-day Europeans. _Nature_ 513, 409–413 (2014). Article  CAS  PubMed  PubMed Central 

Google Scholar  * Wilde, S. et al. Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y. _Proc. Natl Acad. Sci. USA_ 111, 4832–4837

(2014). THIS STUDY USED ANCIENT DNA DATA FOR ALLELES KNOWN TO BE INVOLVED IN HUMAN PIGMENTATION VARIATION TO IDENTIFY A HISTORY OF POSITIVE NATURAL SELECTION AND ESTIMATE THE STRENGTH OF

SELECTION FOR EACH LOCUS. Article  CAS  PubMed  PubMed Central  Google Scholar  * Jeong, C. et al. Long-term genetic stability and a high-altitude East Asian origin for the peoples of the

high valleys of the Himalayan arc. _Proc. Natl Acad. Sci. USA_ 113, 7485–7490 (2016). THIS IS AN ANCIENT GENOME STUDY OF EIGHT INDIVIDUALS FROM NEPAL (3,150–1,250 YEARS BP ) THAT FOUND

STAGGERED APPEARANCES AND FREQUENCY INCREASES FOR SEVERAL GENETIC VARIANTS KNOWN FROM STUDIES OF MODERN REGIONAL POPULATIONS TO BE ASSOCIATED WITH PHYSIOLOGICAL ADAPTATION TO HIGH ALTITUDE.

Article  CAS  PubMed  PubMed Central  Google Scholar  * Lorenzo, F. R. et al. A genetic mechanism for Tibetan high-altitude adaptation. _Nat. Genet._ 46, 951–956 (2014). Article  CAS  PubMed

  PubMed Central  Google Scholar  * Peng, Y. et al. Genetic variations in Tibetan populations and high-altitude adaptation at the Himalayas. _Mol. Biol. Evol._ 28, 1075–1081 (2011). Article

  CAS  PubMed  Google Scholar  * Ralph, P. & Coop, G. Parallel adaptation: one or many waves of advance of an advantageous allele? _Genetics_ 186, 647–668 (2010). Article  PubMed  PubMed

Central  Google Scholar  * Novembre, J., Galvani, A. P. & Slatkin, M. The geographic spread of the CCR5 Δ32 HIV-resistance allele. _PLoS Biol._ 3, e339 (2005). Article  PubMed  PubMed

Central  CAS  Google Scholar  * Richards, M. P., Schulting, R. J. & Hedges, R. E. M. Archaeology: sharp shift in diet at onset of Neolithic. _Nature_ 425, 366–366 (2003). Article  CAS 

PubMed  Google Scholar  * Chaplin, G. & Jablonski, N. G. The human environment and the vitamin D compromise: Scotland as a case study in human biocultural adaptation and disease

susceptibility. _Hum. Biol._ 85, 529–552 (2013). Article  PubMed  Google Scholar  * Druzhkova, A. S. et al. Ancient DNA analysis affirms the canid from Altai as a primitive dog. _PLoS ONE_

8, e57754 (2013). Article  CAS  PubMed  PubMed Central  Google Scholar  * Snir, A. et al. The origin of cultivation and proto-weeds, long before Neolithic farming. _PLoS ONE_ 10, e0131422

(2015). Article  PubMed  PubMed Central  CAS  Google Scholar  * Boivin, N. L. et al. Ecological consequences of human niche construction: examining long-term anthropogenic shaping of global

species distributions. _Proc. Natl Acad. Sci. USA_ 113, 6388–6396 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Copeland, L., Blazek, J., Salman, H. & Tang, M. C. Form

and functionality of starch. _Food Hydrocoll._ 23, 1527–1534 (2009). Article  CAS  Google Scholar  * Gerbault, P. et al. Evolution of lactase persistence: an example of human niche

construction. _Phil. Trans. R. Soc. B._ 366, 863–877 (2011). Article  CAS  PubMed  PubMed Central  Google Scholar  * Campbell, A. K., Waud, J. P. & Matthews, S. B. The molecular basis of

lactose intolerance. _Sci. Prog._ 88, 157–202 (2005). Article  CAS  PubMed  Google Scholar  * Tishkoff, S. A. et al. Convergent adaptation of human lactase persistence in Africa and Europe.

_Nat. Genet._ 39, 31–40 (2007). Article  CAS  PubMed  Google Scholar  * Itan, Y., Powell, A., Beaumont, M. A., Burger, J. & Thomas, M. G. The origins of lactase persistence in Europe.

_PLoS Comput. Biol._ 5, e1000491 (2009). Article  PubMed  PubMed Central  CAS  Google Scholar  * Hofmanová, Z. et al. Early farmers from across Europe directly descended from Neolithic

Aegeans. _Proc. Natl Acad. Sci. USA_ 113, 6886–6891 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Burger, J., Kirchner, M., Bramanti, B., Haak, W. & Thomas, M. G.

Absence of the lactase-persistence-associated allele in early Neolithic Europeans. _Proc. Natl Acad. Sci. USA_ 104, 3736–3741 (2007). THIS WAS THE FIRST ANCIENT DNA-BASED STUDY OF THE

HISTORY OF THE EUROPEAN LACTASE PERSISTENCE ALLELE; THIS STUDY REPORTED THAT THE ALLELE WAS NOT PRESENT IN EIGHT EARLY NEOLITHIC INDIVIDUALS (!7,500 YEARS BP ) FROM FOUR GEOGRAPHIC SITES,

SUGGESTING THAT THE ABILITY OF INDIVIDUALS TO DIGEST LACTOSE ACROSS THEIR LIFETIMES LIKELY POST-DATED THE ORIGIN AND SPREAD OF EUROPEAN DAIRYING PRACTICES. Article  CAS  PubMed  PubMed

Central  Google Scholar  * Craig, O. E. et al. Did the first farmers of central and eastern Europe produce dairy foods? _Antiquity_ 79, 882–894 (2005). Article  Google Scholar  * Copley, M.

S. et al. Direct chemical evidence for widespread dairying in prehistoric Britain. _Proc. Natl Acad. Sci. USA_ 100, 1524–1529 (2003). Article  CAS  PubMed  PubMed Central  Google Scholar  *

Treuil, R. _Dikili Tash, village préhistorique de Macédoine orientale. 1, Fouilles de Jean Deshayes (1961–1975), vol. 2, Bulletin de Correspondance Hellénique Supplément 37_ (Ecole française

d'Athènes, 2004). Google Scholar  * Salque, M. et al. Earliest evidence for cheese making in the sixth millennium BC in northern Europe. _Nature_ 493, 522–525 (2013). Article  CAS 

PubMed  Google Scholar  * Perry, G. H. et al. Diet and the evolution of human amylase gene copy number variation. _Nat. Genet._ 39, 1256–1260 (2007). Article  CAS  PubMed  PubMed Central 

Google Scholar  * Inchley, C. E. et al. Selective sweep on human amylase genes postdates the split with Neanderthals. _Sci. Rep._ 6, 37198 (2016). Article  CAS  PubMed  PubMed Central 

Google Scholar  * Perry, G. H., Kistler, L., Kelaita, M. A. & Sams, A. J. Insights into hominin phenotypic and dietary evolution from ancient DNA sequence data. _J. Hum. Evol._ 79, 55–63

(2015). Article  PubMed  Google Scholar  * Mathias, R. A. et al. Adaptive evolution of the _FADS_ gene cluster within Africa. _PLoS ONE_ 7, e44926 (2012). Article  CAS  PubMed  PubMed

Central  Google Scholar  * Paul, B. D. & Snyder, S. H. The unusual amino acid l-ergothioneine is a physiologic cytoprotectant. _Cell Death Differ._ 17, 1134–1140 (2010). Article  CAS 

PubMed  Google Scholar  * Huff, C. D. et al. Crohn's disease and genetic hitchhiking at IBD5. _Mol. Biol. Evol._ 29, 101–111 (2012). Article  CAS  PubMed  Google Scholar  * Lindo, J. et

al. A time transect of exomes from a Native American population before and after European contact. _Nat. Commun._ 7, 13175 (2016). IN THIS PAPER, THE AUTHORS SEQUENCED THE EXOMES OF 25

ANCIENT FIRST NATIONS INDIVIDUALS (!6,200–800 YEARS BP ) FROM BRITISH COLUMBIA, CANADA, TO IDENTIFY AN _HLA-DQA1_ GENE HAPLOTYPE WITH A SUBSTANTIAL FREQUENCY DIFFERENCE COMPARED WITH THE

TSIMSHIAN DESCENDANT POPULATION LIVING IN THE REGION TODAY, POTENTIALLY REFLECTING ADAPTATION TO DISEASE OUTBREAKS ASSOCIATED WITH EUROPEAN COLONIZATION (WHICH POST-DATED THE ANCIENT DNA

TIME SERIES). Article  CAS  PubMed  PubMed Central  Google Scholar  * Harkins, K. M. & Stone, A. C. Ancient pathogen genomics: insights into timing and adaptation. _J. Hum. Evol._ 79,

137–149 (2015). Article  PubMed  Google Scholar  * Bos, K. I. et al. Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis. _Nature_ 514, 494–497

(2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Roffey, S. et al. Investigation of a medieval pilgrim burial excavated from the leprosarium of St Mary Magdalen Winchester.

_PLoS Negl. Trop. Dis._ 11, e0005186 (2017). Article  PubMed  PubMed Central  Google Scholar  * Spyrou, M. A. et al. Historical _Y. pestis_ genomes reveal the European Black Death as the

source of ancient and modern plague pandemics. _Cell Host Microbe_ 19, 874–881 (2016). Article  CAS  PubMed  Google Scholar  * Marciniak, S. et al. _Plasmodium falciparum_ malaria in 1

st−2nd century CE southern Italy. _Curr. Biol._ 26, R1220–R1222 (2016). Article  CAS  PubMed  Google Scholar  * Gelabert, P. et al. Mitochondrial DNA from the eradicated European _Plasmodium

vivax_ and _P. falciparum_ from 70-year-old slides from the Ebro Delta in Spain. _Proc. Natl Acad. Sci. USA_ 113, 11495–11500 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  *

Duggan, A. T. et al. 17 th century Variola virus reveals the recent history of smallpox. _Curr. Biol._ 26, 3407–3412 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Devault,

A. M. et al. Second-pandemic strain of _Vibrio cholerae_ from the Philadelphia cholera outbreak of 1849. _N. Engl. J. Med._ 370, 334–340 (2014). Article  CAS  PubMed  Google Scholar  *

Devault, A. M. et al. A molecular portrait of maternal sepsis from Byzantine Troy. _eLife_ 6, e20983 (2017). Article  PubMed  PubMed Central  Google Scholar  * Warinner, C. et al. Pathogens

and host immunity in the ancient human oral cavity. _Nat. Genet._ 46, 336–344 (2014). THIS STUDY REPORTED ANCIENT DNA RESULTS FROM DENTAL CALCULUS COLLECTED FROM FOUR EUROPEAN INDIVIDUALS

(!1,000–750 YEARS BP ), INCLUDING DOCUMENTATION OF THE PRESENCE OF VARIOUS PATHOGENIC BACTERIA AND PRODUCING DIRECT EVIDENCE THAT PIG, SHEEP, WHEAT AND CRUCIFEROUS VEGETABLES WERE CONSUMED

AS PART OF THE DIET. Article  CAS  PubMed  PubMed Central  Google Scholar  * Rasmussen, S. et al. Early divergent strains of _Yersinia pestis_ in Eurasia 5,000 years ago. _Cell_ 163, 571–582

(2015). THIS PAPER SEQUENCED SEVEN EURASIAN PLAGUE ( _YERSINIA PESTIS_ ) ANCIENT GENOMES (!5,000–2,800 YEARS BP ) AND, AMONG OTHER FINDINGS, DISCOVERED THAT A GENE ENCODING A PROTEIN

NECESSARY FOR _Y. PESTIS_ VIABILITY IN THE FLEA GUT WAS ABSENT FROM GENOMES PRIOR TO !3,600 YEARS BP ; THE SUBSEQUENT ACQUISITION OF THIS GENE THROUGH HORIZONTAL TRANSFER LIKELY HELPED

FACILITATE THE BUBONIC PLAGUE TRANSMISSION CYCLE. Article  CAS  PubMed  PubMed Central  Google Scholar  * Hinnebusch, B. J. et al. Role of _Yersinia_ murine toxin in survival of _Yersinia

pestis_ in the midgut of the flea vector. _Science_ 296, 733–735 (2002). Article  CAS  PubMed  Google Scholar  * Bos, K. I. et al. A draft genome of _Yersinia pestis_ from victims of the

Black Death. _Nature_ 478, 506–510 (2011). Article  CAS  PubMed  PubMed Central  Google Scholar  * Hummel, S., Schmidt, D., Kremeyer, B., Herrmann, B. & Oppermann, M. Detection of the

CCR5-Δ32 HIV resistance gene in Bronze Age skeletons. _Genes Immun._ 6, 371–374 (2005). Article  CAS  PubMed  Google Scholar  * Wolpoff, M. H., Thorne, A. G., Smith, F. H., Frayer, D. W.

& Pope, G. G. in _Origins of Anatomically Modern Humans_ (eds Nitecki, M. H. & Nitecki, D.) V.) 175–199 (Plenum Press, 1994). Book  Google Scholar  * Tattersall, I. Out of Africa:

modern human origins special feature: human origins: out of Africa. _Proc. Natl Acad. Sci. USA_ 106, 16018–16021 (2009). Article  CAS  PubMed  PubMed Central  Google Scholar  * Green, R. E.

et al. A draft sequence of the Neandertal genome. _Science_ 328, 710–722 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Reich, D. et al. Genetic history of an archaic

hominin group from Denisova Cave in Siberia. _Nature_ 468, 1053–1060 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Vernot, B. & Akey, J. M. Resurrecting surviving

Neandertal lineages from modern human genomes. _Science_ 343, 1017–1021 (2014). Article  CAS  PubMed  Google Scholar  * Dannemann, M., Prüfer, K. & Kelso, J. Functional implications of

Neandertal introgression in modern humans. _Genome Biol._ 18, 61–72 (2017). Article  PubMed  PubMed Central  Google Scholar  * Prüfer, K. et al. The complete genome sequence of a Neanderthal

from the Altai Mountains. _Nature_ 505, 43–49 (2014). Article  CAS  PubMed  Google Scholar  * Meyer, M. et al. A high-coverage genome sequence from an archaic Denisovan individual.

_Science_ 338, 222–226 (2012). Article  CAS  PubMed  PubMed Central  Google Scholar  * Huerta-Sánchez, E. et al. Altitude adaptation in Tibet caused by introgression of Denisovan-like DNA.

_Nature_ 512, 194–197 (2014). THIS PAPER DEMONSTRATED THAT A GENETIC HAPLOTYPE SURROUNDING THE _EPAS1_ GENE THAT UNDERLIES A PHYSIOLOGICAL ADAPTATION TO HIGH ALTITUDE IN MODERN TIBETANS IS

THE RESULT OF ADAPTIVE INTROGRESSION FROM DENISOVANS OR A RELATED ARCHAIC HOMININ POPULATION. Article  PubMed  PubMed Central  CAS  Google Scholar  * Racimo, F. et al. Archaic adaptive

introgression in TBX15/WARS2. _Mol. Biol. Evol._ 34, 509–524 (2017). CAS  PubMed  Google Scholar  * Skoglund, P. & Jakobsson, M. Archaic human ancestry in East Asia. _Proc. Natl Acad.

Sci. USA_ 108, 18301–18306 (2011). Article  CAS  PubMed  PubMed Central  Google Scholar  * Reich, D. et al. Denisova admixture and the first modern human dispersals into Southeast Asia and

Oceania. _Am. J. Hum. Genet._ 89, 516–528 (2011). Article  CAS  PubMed  PubMed Central  Google Scholar  * Castellano, S. et al. Patterns of coding variation in the complete exomes of three

Neandertals. _Proc. Natl Acad. Sci. USA_ 111, 6666–6671 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Lalueza-Fox, C. et al. A melanocortin 1 receptor allele suggests

varying pigmentation among Neanderthals. _Science_ 318, 1453–1455 (2007). Article  CAS  PubMed  Google Scholar  * Lalueza-Fox, C., Gigli, E., de la Rasilla, M., Fortea, J. & Rosas, A.

Bitter taste perception in Neanderthals through the analysis of the _TAS2R38_ gene. _Biol. Lett._ 5, 809–811 (2009). Article  PubMed  PubMed Central  Google Scholar  * McCoy, R. C.,

Wakefield, J. & Akey, J. M. Impacts of Neanderthal-introgressed sequences on the landscape of human gene expression. _Cell_ 168, 916–927 (2017). Article  CAS  PubMed  PubMed Central 

Google Scholar  * Simonti, C. N. et al. The phenotypic legacy of admixture between modern humans and Neandertals. _Science_ 351, 737–741 (2016). THIS STUDY USED ELECTRONIC HEALTH RECORD

PHENOTYPES FROM A LARGE SAMPLE OF MODERN HUMAN PATIENTS TO ASSOCIATE ALLELES ORIGINALLY INTROGRESSED FROM NEANDERTALS WITH INCREASED RISK OF DEPRESSION, SKIN LESIONS ASSOCIATED WITH SUN

EXPOSURE (ACTINIC KERATOSIS), AND OTHER PHENOTYPES. Article  CAS  PubMed  PubMed Central  Google Scholar  * Gittelman, R. M. et al. Archaic hominin admixture facilitated adaptation to

Out-of-Africa environments. _Curr. Biol._ 26, 3375–3382 (2016). THIS PAPER ANALYSED 126 GENOMIC REGIONS CONTAINING STRONG SIGNATURES OF ADAPTIVE INTROGRESSION FROM ARCHAIC HOMININS

IDENTIFIED IN A SAMPLE OF GEOGRAPHICALLY DIVERSE HUMAN POPULATIONS; THESE LOCI ARE SIGNIFICANTLY ENRICHED FOR GENES INVOLVED IN THE IMMUNE RESPONSE AND ALSO CONTAIN MULTIPLE GENES WITH KNOWN

ROLES IN SKIN PIGMENTATION. Article  CAS  PubMed  PubMed Central  Google Scholar  * Racimo, F., Sankararaman, S., Nielsen, R. & Huerta-Sánchez, E. Evidence for archaic adaptive

introgression in humans. _Nat. Rev. Genet._ 16, 359–371 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Sankararaman, S. et al. The landscape of Neandertal ancestry in

present-day humans. _Nature_ 507, 354–357 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Vernot, B. et al. Excavating Neandertal and Denisovan DNA from the genomes of

Melanesian individuals. _Science_ 352, 235–239 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Fumagalli, M. et al. Greenlandic Inuit show genetic signatures of diet and

climate adaptation. _Science_ 349, 1343–1347 (2015). Article  CAS  PubMed  Google Scholar  * Gburcik, V., Cawthorn, W. P., Nedergaard, J., Timmons, J. A. & Cannon, B. An essential role

for Tbx15 in the differentiation of brown and 'brite' but not white adipocytes. _Am. J. Physiol. Endocrinol. Metab._ 303, E1053–E1060 (2012). Article  CAS  PubMed  Google Scholar 

* Deschamps, M. et al. Genomic signatures of selective pressures and introgression from archaic hominins at human innate immunity genes. _Am. J. Hum. Genet._ 98, 5–21 (2016). Article  CAS 

PubMed  PubMed Central  Google Scholar  * Enard, D. & Petrov, D. A. RNA viruses drove adaptive introgressions between Neanderthals and modern humans. Preprint at

_bioRxiv_http://dx.doi.org/10.1101/120477 (2017). * Abi-Rached, L. et al. The shaping of modern human immune systems by multiregional admixture with archaic humans. _Science_ 334, 89–94

(2011). Article  CAS  PubMed  PubMed Central  Google Scholar  * Sams, A. J. et al. Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses

in humans. _Genome Biol._ 17, 246–261 (2016). Article  PubMed  PubMed Central  CAS  Google Scholar  * Sullivan, A. P., de Manuel, M., Marques-Bonet, T. & Perry, G. H. An evolutionary

medicine perspective on Neandertal extinction. _J. Hum. Evol._ 108, 62–71 (2017). Article  PubMed  Google Scholar  * Houldcroft, C. J. & Underdown, S. J. Neanderthal genomics suggests a

pleistocene time frame for the first epidemiologic transition. _Am. J. Phys. Anthropol._ 160, 379–388 (2016). Article  PubMed  Google Scholar  * Key, F. M., Teixeira, J. C., de Filippo, C.

& Andrés, A. M. Advantageous diversity maintained by balancing selection in humans. _Curr. Opin. Genet. Dev._ 29, 45–51 (2014). Article  CAS  PubMed  Google Scholar  * Nédélec, Y. et al.

Genetic ancestry and natural selection drive population differences in immune responses to pathogens. _Cell_ 167, 657–669 (2016). Article  CAS  PubMed  Google Scholar  * Quach, H. et al.

Genetic adaptation and Neandertal admixture shaped the immune system of human populations. _Cell_ 167, 643–656.e17 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Park, S. D.

E. et al. Genome sequencing of the extinct Eurasian wild aurochs, _Bos primigenius_, illuminates the phylogeography and evolution of cattle. _Genome Biol._ 16, 234–249 (2015). Article 

PubMed  PubMed Central  CAS  Google Scholar  * Loog, L. et al. Inferring allele frequency trajectories from ancient DNA indicates that selection on a chicken gene coincided with changes in

medieval husbandry practices. _Mol. Biol. Evol._ http://dx.doi.org/10.1093/molbev/msx142 (2017). THIS STUDY OF DOMESTIC CHICKENS CONNECTED THE ANCIENT DNA-INFORMED TIMING OF A SIGNIFICANT

CHANGE IN FREQUENCY FOR AN ALLELE ASSOCIATED WITH INCREASED EGG PRODUCTION TO CONCOMITANT INCREASES IN THE INTENSITY OF CHICKEN HUSBANDRY AS DOCUMENTED BY HISTORICAL AND ARCHAEOLOGICAL

RECORDS. * MacHugh, D. E., Larson, G. & Orlando, L. Taming the past: ancient DNA and the study of animal domestication. _Annu. Rev. Anim. Biosci._ 5, 329–351 (2017). Article  CAS  PubMed

  Google Scholar  * Ramos-Madrigal, J. et al. Genome sequence of a 5,310-year-old maize cob provides insights into the early stages of maize domestication. _Curr. Biol._ 26, 3195–3201

(2016). THIS STUDY IDENTIFIED A MIX OF ANCESTRAL AND DERIVED FUNCTIONAL GENETIC VARIANTS IN MAIZE FROM MEXICO !5,300 YEARS BP , HIGHLIGHTING THE GRADUAL TEMPORAL PROCESS OF TRAIT EVOLUTION

IN THIS DOMESTIC SPECIES. Article  CAS  PubMed  Google Scholar  * Schubert, M. et al. Prehistoric genomes reveal the genetic foundation and cost of horse domestication. _Proc. Natl Acad.

Sci. USA_ 111, E5661–E5669 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Ollivier, M. et al. _Amy2B_ copy number variation reveals starch diet adaptations in ancient

European dogs. _R. Soc. Open Sci._ 3, 160449 (2016). Article  PubMed  PubMed Central  CAS  Google Scholar  * Librado, P. et al. Tracking the origins of Yakutian horses and the genetic basis

for their fast adaptation to subarctic environments. _Proc. Natl Acad. Sci. USA_ 112, E6889–E6897 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Jaenicke-Després, V. et al.

Early allelic selection in maize as revealed by ancient DNA. _Science_ 302, 1206–1208 (2003). Article  CAS  PubMed  Google Scholar  * Flink, L. G. et al. Establishing the validity of

domestication genes using DNA from ancient chickens. _Proc. Natl Acad. Sci. USA_ 111, 6184–6189 (2013). Article  CAS  Google Scholar  * West, B. & Zhou, B.-X. Did chickens go North? New

evidence for domestication. _J. Archaeol. Sci._ 15, 515–533 (1988). Article  Google Scholar  * Librado, P. et al. Ancient genomic changes associated with domestication of the horse.

_Science_ 356, 442–445 (2017). Article  CAS  PubMed  Google Scholar  * Outram, A. K. et al. The earliest horse harnessing and milking. _Science_ 323, 1332–1335 (2009). Article  CAS  PubMed 

Google Scholar  * Ludwig, A. et al. Coat colour variation at the beginning of horse domestication. _Science_ 324, 485 (2009). Article  CAS  PubMed  PubMed Central  Google Scholar  * Ludwig,

A. et al. Twenty-five thousand years of fluctuating selection on leopard complex spotting and congenital night blindness in horses. _Phil. Trans. R. Soc. B._ 370, 20130386 (2014). Article 

CAS  Google Scholar  * Ottoni, C. et al. The palaeogenetics of cat dispersal in the ancient world. _Nat. Ecol. Evol._ 1, 0139 (2017). Article  Google Scholar  * Axelsson, E. et al. The

genomic signature of dog domestication reveals adaptation to a starch-rich diet. _Nature_ 495, 360–364 (2013). Article  CAS  PubMed  Google Scholar  * Arendt, M., Cairns, K. M., Ballard, J.

W. O., Savolainen, P. & Axelsson, E. Diet adaptation in dog reflects spread of prehistoric agriculture. _Heredity_ 117, 301–306 (2016). Article  CAS  PubMed  PubMed Central  Google

Scholar  * Botigué, L. R. et al. Ancient European dog genomes reveal continuity since the Early Neolithic. _Nat. Commun._ 8, 16082 (2017). Article  PubMed  PubMed Central  CAS  Google

Scholar  * Frantz, L. A. F. et al. Genomic and archaeological evidence suggest a dual origin of domestic dogs. _Science_ 352, 1228–1231 (2016). Article  CAS  PubMed  Google Scholar  *

Kistler, L., Ware, R., Smith, O., Collins, M. & Allaby, R. G. A new model for ancient DNA decay based on paleogenomic meta-analysis. _Nucleic Acids Res._ 45, 6310–6320 (2017). Article 

CAS  PubMed  PubMed Central  Google Scholar  * Fehren-Schmitz, L. & Georges, L. Ancient DNA reveals selection acting on genes associated with hypoxia response in pre-Columbian Peruvian

Highlanders in the last 8500 years. _Sci. Rep._ 6, 23485 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Sullivan, A. P., Bird, D. W. & Perry, G. H. Human behaviour as a

long-term ecological driver of non-human evolution. _Nat. Ecol. Evol._ 1, 0065 (2017). Article  Google Scholar  * Noonan, J. P. et al. Sequencing and analysis of Neanderthal genomic DNA.

_Science_ 314, 1113–1118 (2006). Article  CAS  PubMed  PubMed Central  Google Scholar  * Green, R. E. et al. Analysis of one million base pairs of Neanderthal DNA. _Nature_ 444, 330–336

(2006). Article  CAS  PubMed  Google Scholar  * Ramírez, O. et al. Paleogenomics in a temperate environment: shotgun sequencing from an extinct Mediterranean Caprine. _PLoS ONE_ 4, e5670

(2009). Article  PubMed  PubMed Central  CAS  Google Scholar  * Miller, W. et al. Sequencing the nuclear genome of the extinct woolly mammoth. _Nature_ 456, 387–390 (2008). Article  CAS 

PubMed  Google Scholar  * Lambert, D. M. & Millar, C. D. Evolutionary biology: ancient genomics is born. _Nature_ 444, 275–276 (2006). Article  CAS  PubMed  Google Scholar  * Wall, J. D.

& Kim, S. K. Inconsistencies in Neanderthal genomic DNA sequences. _PLoS Genet._ 3, 1862–1866 (2007). Article  CAS  PubMed  Google Scholar  * Rasmussen, M. et al. Ancient human genome

sequence of an extinct Palaeo-Eskimo. _Nature_ 463, 757–762 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Lazaridis, I. et al. Genomic insights into the origin of farming

in the ancient Near East. _Nature_ 536, 419–424 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Pinhasi, R. et al. Optimal ancient DNA yields from the inner ear part of the

human petrous bone. _PLoS ONE_ 10, e0129102 (2015). Article  PubMed  PubMed Central  CAS  Google Scholar  * Gansauge, M.-T. & Meyer, M. Single-stranded DNA library preparation for the

sequencing of ancient or damaged DNA. _Nat. Protoc._ 8, 737–748 (2013). Article  PubMed  CAS  Google Scholar  * Carpenter, M. L. et al. Pulling out the 1%: whole-genome capture for the

targeted enrichment of ancient DNA sequencing libraries. _Am. J. Hum. Genet._ 93, 852–864 (2013). Article  CAS  PubMed  PubMed Central  Google Scholar  * Hofreiter, M. et al. The future of

ancient DNA: technical advances and conceptual shifts. _BioEssays_ 37, 284–293 (2015). Article  PubMed  Google Scholar  * Gron, K. J. et al. Cattle management for dairying in

Scandinavia's earliest Neolithic. _PLoS ONE_ 10, e0131267 (2015). Article  PubMed  PubMed Central  CAS  Google Scholar  * Zeder, M. A. & Hesse, B. The initial domestication of goats

(_Capra hircus_) in the Zagros mountains 10,000 years ago. _Science_ 287, 2254–2257 (2000). Article  CAS  PubMed  Google Scholar  * Cramp, L. J. E. et al. Neolithic dairy farming at the

extreme of agriculture in northern Europe. _Proc. Biol. Sci._ 281, 20140819 (2014). Article  PubMed  PubMed Central  Google Scholar  * Warinner, C. et al. Direct evidence of milk consumption

from ancient human dental calculus. _Sci. Rep._ 4, 7104 (2015). Article  CAS  Google Scholar  * Yang, Y. et al. Proteomics evidence for kefir dairy in Early Bronze Age China. _J. Archaeol.

Sci._ 45, 178–186 (2014). Article  CAS  Google Scholar  * Burbano, H. A. et al. Targeted investigation of the Neandertal genome by array-based sequence capture. _Science_ 328, 723–725

(2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Rasmussen, M. et al. An Aboriginal Australian genome reveals separate human dispersals into Asia. _Science_ 334, 94–98 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar  * Keller, A. et al. New insights into the Tyrolean Iceman's origin and phenotype as inferred by whole-genome sequencing. _Nat.

Commun._ 3, 698 (2012). Article  CAS  PubMed  Google Scholar  * Skoglund, P. et al. Origins and genetic legacy of Neolithic farmers and hunter-gatherers in Europe. _Science_ 336, 466–469

(2012). Article  CAS  PubMed  Google Scholar  * Fu, Q. et al. DNA analysis of an early modern human from Tianyuan Cave, China. _Proc. Natl Acad. Sci. USA_ 110, 2223–2227 (2013). Article  CAS

  PubMed  PubMed Central  Google Scholar  * Fu, Q. et al. Genome sequence of a 45,000-year-old modern human from western Siberia. _Nature_ 514, 445–449 (2014). Article  CAS  PubMed  PubMed

Central  Google Scholar  * Schroeder, H. et al. Genome-wide ancestry of 17 th-century enslaved Africans from the Caribbean. _Proc. Natl Acad. Sci. USA_ 112, 3669–3673 (2015). Article  CAS 

PubMed  PubMed Central  Google Scholar  * Malaspinas, A.-S. et al. Two ancient human genomes reveal Polynesian ancestry among the indigenous Botocudos of Brazil. _Curr. Biol._ 24,

R1035–R1037 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Raghavan, M. et al. Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans. _Nature_ 505,

87–91 (2014). Article  CAS  PubMed  Google Scholar  * Rasmussen, M. et al. The genome of a Late Pleistocene human from a Clovis burial site in western Montana. _Nature_ 506, 225–229 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar  * Seguin-Orlando, A. et al. Genomic structure in Europeans dating back at least 36,200 years. _Science_ 346, 1113–1118 (2014). Article 

CAS  PubMed  Google Scholar  * Skoglund, P. et al. Genomic diversity and admixture differs for Stone-Age Scandinavian foragers and farmers. _Science_ 344, 747–750 (2014). Article  CAS 

PubMed  Google Scholar  * Fu, Q. et al. An early modern human from Romania with a recent Neanderthal ancestor. _Nature_ 524, 216–219 (2015). Article  CAS  PubMed  PubMed Central  Google

Scholar  * Gallego Llorente, M. et al. Ancient Ethiopian genome reveals extensive Eurasian admixture in Eastern Africa. _Science_ 350, 820–822 (2015). Article  CAS  PubMed  Google Scholar  *

Olalde, I. et al. A common genetic origin for early farmers from Mediterranean Cardial and Central European LBK cultures. _Mol. Biol. Evol._ 32, 3132–3142 (2015). CAS  PubMed  PubMed

Central  Google Scholar  * Raghavan, M. et al. Genomic evidence for the Pleistocene and recent population history of Native Americans. _Science_ 349, aab3884 (2015). Article  PubMed  PubMed

Central  CAS  Google Scholar  * Sawyer, S. et al. Nuclear and mitochondrial DNA sequences from two Denisovan individuals. _Proc. Natl Acad. Sci. USA_ 112, 15696–15700 (2015). Article  CAS 

PubMed  PubMed Central  Google Scholar  * Rasmussen, M. et al. The ancestry and affiliations of Kennewick Man. _Nature_ 523, 455–458 (2015). Article  PubMed  PubMed Central  Google Scholar 

* Martiniano, R. et al. Genomic signals of migration and continuity in Britain before the Anglo-Saxons. _Nat. Commun._ 7, 10326 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar 

* Schiffels, S. et al. Iron Age and Anglo-Saxon genomes from East England reveal British migration history. _Nat. Commun._ 7, 10408 (2016). Article  CAS  PubMed  PubMed Central  Google

Scholar  * Fu, Q. et al. The genetic history of Ice Age Europe. _Nature_ 534, 200–205 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Gallego Llorente, M. et al. The genetics

of an early Neolithic pastoralist from the Zagros, Iran. _Sci. Rep._ 6, 31326 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Kılınç, G. M. et al. The demographic

development of the first farmers in Anatolia. _Curr. Biol._ 26, 2659–2666 (2016). Article  PubMed  PubMed Central  CAS  Google Scholar  * Omrak, A. et al. Genomic evidence establishes

Anatolia as the source of the European Neolithic gene pool. _Curr. Biol._ 26, 270–275 (2016). Article  CAS  PubMed  Google Scholar  * Meyer, M. et al. Nuclear DNA sequences from the Middle

Pleistocene Sima de los Huesos hominins. _Nature_ 531, 504–507 (2016). Article  CAS  PubMed  Google Scholar  * Skoglund, P. et al. Genomic insights into the peopling of the Southwest

Pacific. _Nature_ 538, 510–513 (2016). Article  PubMed  PubMed Central  CAS  Google Scholar  * Jones, E. R. et al. The Neolithic transition in the Baltic was not driven by admixture with

early European farmers. _Curr. Biol._ 27, 576–582 (2017). Article  CAS  PubMed  PubMed Central  Google Scholar  * Unterländer, M. et al. Ancestry and demography and descendants of Iron Age

nomads of the Eurasian Steppe. _Nat. Commun._ 8, 14615 (2017). Article  PubMed  PubMed Central  Google Scholar  * Lipson, M. et al. Parallel ancient genomic transects reveal complex

population history of early European farmers. Preprint at _bioRxiv_http://dx.doi.org/10.1101/114488 (2017). * Lindo, J. et al. Ancient individuals from the North American Northwest Coast

reveal 10,000 years of regional genetic continuity. _Proc. Natl Acad. Sci. USA_ 114, 4093–4098 (2017). Article  CAS  PubMed  PubMed Central  Google Scholar  * Kennett, D. J. et al.

Archaeogenomic evidence reveals prehistoric matrilineal dynasty. _Nat. Commun._ 8, 14115 (2017). Article  CAS  PubMed  PubMed Central  Google Scholar  * Mathieson, I. et al. The genomic

history of southeastern Europe. Preprint at _bioRxiv_http://dx.doi.org/10.1101/135616 (2017). * Martiniano, R. et al. The population genomics of archaeological transition in west Iberia:

Investigation of ancient substructure using imputation and haplotype-based methods. _PLoS Genet._ 13, e1006852 (2017). Article  PubMed  PubMed Central  CAS  Google Scholar  * Siska, V. et

al. Genome-wide data from two early Neolithic East Asian individuals dating to 7700 years ago. _Sci. Adv._ 3, e1601877 (2017). Article  PubMed  PubMed Central  Google Scholar  * Haber, M. et

al. Continuity and admixture in the last five millennia of Levantine history from ancient Canaanite and present-day Lebanese genome sequences. _Am. J. Hum. Genet._

http://dx.doi.org/10.1016/j.ajhg.2017.06.013 (2017). * Schuenemann, V. J. et al. Ancient Egyptian mummy genomes suggest an increase of Sub-Saharan African ancestry in post-Roman periods.

_Nat. Commun._ 8, 15694 (2017). Article  CAS  PubMed  PubMed Central  Google Scholar  * Schlebusch, C. M. et al. Ancient genomes from southern Africa pushes modern human divergence beyond

260,000 years ago. Preprint at _bioRxiv_http://dx.doi.org/10.1101/145409 (2017). * Mittnik, A. et al. The genetic history of northern Europe. Preprint at

_bioRxiv_http://dx.doi.org/10.1101/113241 (2017). * Slon, V. et al. A fourth Denisovan individual. _Sci. Adv._ 3, e1700186 (2017). Article  PubMed  PubMed Central  CAS  Google Scholar  *

Kuhlwilm, M. et al. Ancient gene flow from early modern humans into Eastern Neanderthals. _Nature_ 530, 429–433 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  Download

references ACKNOWLEDGEMENTS The authors thank C. Bergey and R. George for discussion about the manuscript. This work was supported by grants from the National Science Foundation (BCS-1554834

and BCS-1317163; to G.H.P.). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Anthropology, Pennsylvania State University, University Park, 16802, Pennsylvania, USA Stephanie

Marciniak & George H. Perry * Department of Biology, Pennsylvania State University, University Park, 16802, Pennsylvania, USA George H. Perry * Huck Institutes of the Life Sciences,

Pennsylvania State University, University Park, 16802, Pennsylvania, USA George H. Perry Authors * Stephanie Marciniak View author publications You can also search for this author inPubMed 

Google Scholar * George H. Perry View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS The authors contributed equally to all aspects of this

manuscript. CORRESPONDING AUTHOR Correspondence to George H. Perry. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION S1 (TABLE) Spatiotemporal frequencies of the European lactase persistence allele. (PDF 186 kb) POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR

FIG. 2 POWERPOINT SLIDE FOR FIG. 3 POWERPOINT SLIDE FOR FIG. 4 POWERPOINT SLIDE FOR FIG. 5 POWERPOINT SLIDE FOR TABLE 1 GLOSSARY * Adaptation A process of phenotypic and corresponding

genetic change over time for traits that confer increased reproductive fitness in a given environmental context. * Positive natural selection A mechanism of evolution in which a genetically

mediated trait that confers a relative fitness advantage increases in frequency over time because of that advantage. In this Review, we refer to positive selection as an adaptive process

that can act on new or previously existing genetic variants. * Phenotype Physical traits of an organism; often refers to externally visible traits but may include internal and microscopic or

biochemical traits. * Ancient DNA DNA from palaeontological, archaeological, or historical but pre-modern biological specimens that is often damaged and degraded and recovered in small

quantities. * Exome All or nearly all protein-coding gene regions of the nuclear genome; in humans, representing approximately 1% of the genome. * Single-nucleotide polymorphism (SNP). A

single position in the reference genome at which the specific nucleotide present (thymine, guanine, cytosine, or adenine) varies among individuals in a population or species. * Archaic

hominins Now-extinct populations or species that are distinct from anatomically modern humans but that share a more recent common ancestor with modern humans than with chimpanzees — for

example, Neandertals and Denisovans. * Anatomically modern humans Hominins recognizable phenotypically as early members of our own species, _Homo sapiens_, first appearing >200,000 years

BP in Africa. * Adaptive introgression The process of a genetic variant that was originally introduced into a population via admixture increasing in frequency by positive natural selection

because it confers a fitness advantage. * Genetic drift Changes in genetic variation over time that are due to random (chance) processes, apart from natural selection. * Gene flow Movement

of genetic variation between populations, for example, through migration or admixture. * Neolithic A cultural period in human prehistory characterized by early technological and demographic

shifts associated with the transition to farming and pastoralism, occurring at different times across regions. * Domestication A process of plant and animal evolution mediated by human

selection for particular phenotypes (artificial selection), sometimes combined with commensal adaptation to human-constructed niches. * Biocultural adaptation The process of interaction

between human cultural and adaptive biological change (for example, dairying and the ability of adults to digest milk sugars). * Zoonotic The ability of a pathogen to be directly or

indirectly transmitted to humans from animals sharing the same habitat. * Admixture Interbreeding between previously isolated populations. RIGHTS AND PERMISSIONS Reprints and permissions

ABOUT THIS ARTICLE CITE THIS ARTICLE Marciniak, S., Perry, G. Harnessing ancient genomes to study the history of human adaptation. _Nat Rev Genet_ 18, 659–674 (2017).

https://doi.org/10.1038/nrg.2017.65 Download citation * Published: 11 September 2017 * Issue Date: November 2017 * DOI: https://doi.org/10.1038/nrg.2017.65 SHARE THIS ARTICLE Anyone you

share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the

Springer Nature SharedIt content-sharing initiative