1. Ubelaker, D. H. Prehistoric New World population size: historical review and current appraisal of North American estimates. Am. J. Phys. Anthropol. 45, 661–665 (1976).

2. Crosby, A. W. Virgin soil epidemics as a factor in the aboriginal depopulation in America. William Mary Q. 33, 289–299 (1976).

3. Dobyns, H. F. Disease transfer at contact. Annu. Rev. Anthropol. 22, 273–291 (1993).

4. Acuna-Soto, R., Stahle, D. W., Therrell, M. D., Griffin, R. D. & Cleaveland, M. K. When half of the population died: the epidemic of hemorrhagic fevers of 1576 in Mexico. FEMS Microbiol. Lett. 240, 1–5 (2004).

5. Llamas, B. et al. Ancient mitochondrial DNA provides high-resolution time scale of the peopling of the Americas. Sci. Adv. 2, e1501385 (2016).

6. Lindo, J. et al. A time transect of exomes from a Native American population before and after European contact. Nat. Commun. 7, 13175 (2016).

7. Cook, N. D. & Lovell, W. G. Secret Judgments of God: Old World Disease in Colonial Spanish America (Univ. Oklahoma Press, Norman, 2001).

8. Fields, S. L. Pestilence and Headcolds: Encountering Illness in Colonial Mexico (Columbia Univ. Press, New York, 2008).

9. Ortner, D. J. Identification of Pathological Conditions in Human Skeletal Remains 2nd edn (Academic Press, Cambridge, 2003).

10. Walker, R. S., Sattenspiel, L. & Hill, K. R. Mortality from contact-related epidemics among indigenous populations in Greater Amazonia. Sci. Rep. 5, 14032 (2015).

11. Joralemon, D. New World depopulation and the case of disease. J. Anthropol. Res. 38, 108–127 (1982).

12. Larsen, C. S. In the wake of Columbus: native population biology in the postcontact Americas. Am. J. Phys. Anthropol. 37, 109–154 (1994).

13. Bos, K. I. et al. Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis. Nature 514, 494–497 (2014).

14. Schuenemann, V. J. et al. Genome-wide comparison of medieval and modern Mycobacterium leprae. Science 341, 179–183 (2013).

15. Warinner, C. et al. Pathogens and host immunity in the ancient human oral cavity. Nat. Genet. 46, 336–344 (2014).

16. Bos, K. I. et al. A draft genome of Yersinia pestis from victims of the Black Death. Nature 478, 506–510 (2011).

17. Maixner, F. et al. The 5300-year-old Helicobacter pylori genome of the Iceman. Science 351, 162–165 (2016).

18. Devault, A. M. et al. Ancient pathogen DNA in archaeological samples detected with a microbial detection array. Sci. Rep. 4, 4245 (2014).

19. Bos, K. I. et al. Parallel detection of ancient pathogens via array-based DNA capture. Phil. Trans. R. Soc. B 370, 20130375 (2015).

20. Devault, A. M. et al. A molecular portrait of maternal sepsis from Byzantine Troy. eLife 6, e20983 (2017).

21. Warinner, C. et al. A robust framework for microbial archaeology. Annu. Rev. Genomics Hum. Genet. 18, 321–356 (2017).

22. Key, F. M., Posth, C., Krause, J., Herbig, A. & Bos, K. I. Mining metagenomic data sets for ancient DNA: recommended protocols for authentication. Trends Genet. 33, 508–520 (2017).

23. Jonsson, H., Ginolhac, A., Schubert, M., Johnson, P. L. & Orlando, L. mapDamage2.0: fast approximate Bayesian estimates of ancient DNA damage parameters. Bioinformatics 29, 1682–1684 (2013).

24. Prufer, K. et al. Computational challenges in the analysis of ancient DNA. Genome Biol. 11, R47 (2010).

25. Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990).

26. Peabody, M. A., Van Rossum, T., Lo, R. & Brinkman, F. S. Evaluation of shotgun metagenomics sequence classification methods using in silico and in vitro simulated communities. BMC Bioinforma. 16, 363 (2015).

27. Lindgreen, S., Adair, K. L. & Gardner, P. P. An evaluation of the accuracy and speed of metagenome analysis tools. Sci. Rep. 6, 19233 (2016).

28. Huson, D. H. et al. MEGAN community edition—interactive exploration and analysis of large-scale microbiome sequencing data. PLoS. Comput. Biol. 12, e1004957 (2016).

29. Spores, R. & Robles García, N. A prehispanic (postclassic) capital center in colonial transition: excavations at Yucundaa Pueblo Viejo de Teposcolula, Oaxaca, Mexico. Lat. Am. Antiq. 18, 333–353 (2007).

30. Warinner, C., Robles García, N., Spores, R. & Tuross, N. Disease, demography, and diet in early colonial New Spain: investigation of a sixteenth-century Mixtec cemetery at Teposcolula Yucundaa. Lat. Am. Antiq. 23, 467–489 (2012).

31. Tuross, N., Warinner, C. & Robles García, N. in Yucundaa: La Cuidad Mixteca Yucundaa-Pueblo Viejo de Teposcolula y su Transformación Prehispánica-Colonial Vol. 2 (eds Spores, R. & Robles García, N.) 541–546 (Instituto Nacional de Antropología e Historia, Mexico City, 2014).

32. Acuna-Soto, R., Stahle, D. W., Cleaveland, M. K. & Therrell, M. D. Megadrought and megadeath in 16th century Mexico. Emerg. Infect. Dis. 8, 360–362 (2002).

33. Pickard, D. et al. Molecular characterization of the Salmonella enterica serovar Typhi Vi-typing bacteriophage E1. J. Bacteriol. 190, 2580–2587 (2008).

34. Burbano, H. A. et al. Targeted investigation of the Neandertal genome by array-based sequence capture. Science 328, 723–725 (2010).

35. Fu, Q. et al. DNA analysis of an early modern human from Tianyuan Cave, China. Proc. Natl. Acad. Sci. USA 110, 2223–2227 (2013).

36. Campbell, J. W., Morgan-Kiss, R. M. & Cronan, J. E. Jr A new Escherichia coli metabolic competency: growth on fatty acids by a novel anaerobic beta-oxidation pathway. Mol. Microbiol. 47, 793–805 (2003).

37. Rivera-Chavez, F. et al. Salmonella uses energy taxis to benefit from intestinal inflammation. PLoS. Pathog. 9, e1003267 (2013).

38. Liu, W. Q. et al. Salmonella Paratyphi C: genetic divergence from Salmonella choleraesuis and pathogenic convergence with Salmonella typhi. PLoS ONE 4, e4510 (2009).

39. Tam, C. K., Morris, C. & Hackett, J. The Salmonella enterica serovar Typhi type IVB self-association pili are detached from the bacterial cell by the PilV minor pilus proteins. Infect. Immun. 74, 5414–5418 (2006).

40. Tam, C. K., Hackett, J. & Morris, C. Salmonella enterica serovar Paratyphi C carries an inactive shufflon. Infect. Immun. 72, 22–28 (2004).

41. Campana, M. G., Robles Garcia, N., Ruhli, F. J. & Tuross, N. False positives complicate ancient pathogen identifications using high-throughput shotgun sequencing. BMC Res. Notes 7, 111 (2014).

42. Wood, D. E. & Salzberg, S. L. Kraken: ultrafast metagenomic sequence classification using exact alignments. Genome Biol. 15, R46 (2014).

43. Segata, N. et al. Metagenomic microbial community profiling using unique clade-specific marker genes. Nat. Methods 9, 811–814 (2012).

44. Singer, M. & Clair, S. Syndemics and public health: reconceptualizing disease in bio-social context. Med. Anthropol. Q. 17, 423–441 (2003).

45. Herring, D. A. & Sattenspiel, L. Social contexts, syndemics, and infectious disease in northern Aboriginal populations. Am. J. Hum. Biol. 19, 190–202 (2007).

46. Guy, P. L. Prospects for analyzing ancient RNA in preserved materials. Wiley Interdiscip. Rev. RNA 5, 87–94 (2014).

47. Gal-Mor, O., Boyle, E. C. & Grassl, G. A. Same species, different diseases: how and why typhoidal and non-typhoidal Salmonella enterica serovars differ. Front. Microbiol. 5, 391 (2014).

48. Wain, J., Hendriksen, R. S., Mikoleit, M. L., Keddy, K. H. & Ochiai, R. L. Typhoid fever. Lancet 385, 1136–1145 (2015).

49. Monack, D. M., Mueller, A. & Falkow, S. Persistent bacterial infections: the interface of the pathogen and the host immune system. Nat. Rev. Microbiol. 2, 747–765 (2004).

50. de Sahagún, B. General History of the Things of New Spain: Florentine Codex (School of American Research, Santa Fe, 1950–1982).

51. Zhou, Z. et al. Millennia of genomic stability within the invasive Para C lineage of Salmonella enterica. Preprint at https://www.biorxiv.org/content/early/2017/02/14/105759 (2017).

52. Achtman, M. et al. Multilocus sequence typing as a replacement for serotyping in Salmonella enterica. PLoS. Pathog. 8, e1002776 (2012).

53. National Typhoid and Paratyphoid Fever Surveillance Annual Summary, 2014 (CDC, 2016).

54. Acuna-Soto, R., Romero, L. C. & Maguire, J. H. Large epidemics of hemorrhagic fevers in Mexico 1545–1815. Am. J. Trop. Med. Hyg. 62, 733–739 (2000).

55. Smith, D. C. Gerhard’s distinction between typhoid and typhus and its reception in America, 1833–1860. Bull. Hist. Med. 54, 368–385 (1980).

56. Crump, J. A., Luby, S. P. & Mintz, E. D. The global burden of typhoid fever. Bull. World Health Organ. 82, 346–353 (2004).

58. Burkhardt, S. & Kärkkäinen, J. in Combinatorial Pattern Matching: 12th Annual Symposium, CPM 2001 Jerusalem, Israel, July 1–4, 2001 Proceedings (eds Amihood, A. & Landau, G. M.) 73–85 (Springer, Berlin, 2001).

59. Ma, B., Tromp, J. & Li, M. PatternHunter: faster and more sensitive homology search. Bioinformatics 18, 440–445 (2002).

60. Buchfink, B., Xie, C. & Huson, D. H. Fast and sensitive protein alignment using DIAMOND. Nat. Methods 12, 59–60 (2015).

61. Ning, Z., Cox, A. J. & Mullikin, J. C. SSAHA: a fast search method for large DNA databases. Genome Res. 11, 1725–1729 (2001).

62. Chao, K. M., Pearson, W. R. & Miller, W. Aligning two sequences within a specified diagonal band. Comput. Appl. Biosci. 8, 481–487 (1992).

63. Smith, T. F. & Waterman, M. S. Identification of common molecular subsequences. J. Mol. Biol. 147, 195–197 (1981).

64. Needleman, S. B. & Wunsch, C. D. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J. Mol. Biol. 48, 443–453 (1970).

65. Benson, D. A. et al. GenBank. Nucleic Acids Res. 41, D36–D42 (2013).

66. Dabney, J. et al. Complete mitochondrial genome sequence of a Middle Pleistocene cave bear reconstructed from ultrashort DNA fragments. Proc. Natl. Acad. Sci. USA 110, 15758–15763 (2013).

67. Meyer, M. & Kircher, M. Illumina sequencing library preparation for highly multiplexed target capture and sequencing. Cold Spring Harb. Protoc. 2010, prot5448 (2010).

68. Kircher, M., Sawyer, S. & Meyer, M. Double indexing overcomes inaccuracies in multiplex sequencing on the Illumina platform. Nucleic Acids Res. 40, e3 (2012).

69. Briggs, A. W. et al. Removal of deaminated cytosines and detection of in vivo methylation in ancient DNA. Nucleic Acids Res. 38, e87 (2010).

70. Hodges, E. et al. Hybrid selection of discrete genomic intervals on custom-designed microarrays for massively parallel sequencing. Nat. Protoc. 4, 960–974 (2009).

71. Tamura, K., Stecher, G., Peterson, D., Filipski, A. & Kumar, S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol. Biol. Evol. 30, 2725–2729 (2013).

72. Stamatakis, A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 30, 1312–1313 (2014).

73. R Development Core Team R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna, 2013).

74. Connor, T. R. et al. What’s in a name? Species-wide whole-genome sequencing resolves invasive and noninvasive lineages of Salmonella enterica serotype Paratyphi B. mBio 7, e00527-16 (2016).

75. Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).