Frontiers in Molecular Evolutionary Medicine

  • Stephen C. StearnsEmail author


This paper surveys some of the important insights that molecular evolution has contributed to evolutionary medicine; they include phage therapy, cancer biology, helminth manipulation of the host immune system, quality control of gametes, and pathogen outbreaks. Molecular evolution has helped to revolutionize our understanding of cancer, of autoimmune disease, and of the origin, spread, and pathogenesis of emerging diseases, where it has suggested new therapies, illuminated mechanisms, and revealed historical processes: all have practical therapeutic implications. While much has been accomplished, much remains to be done.


Evolutionary medicine Phage therapy Cancer Autoimmune disease Emerging diseases 



I thank Kevin Hu for insights into synthetic lethals, Ben Chan and Paul Turner for conversations about phage therapy, and Alaric D’Souza and Gunter Wagner for conversations about placental invasiveness and metastatic cancer.


  1. Al-Mekhlafi HM (2018) Yemen in a time of cholera: current situation and challenges. Am J Trop Med Hyg 98:1558CrossRefGoogle Scholar
  2. Ashworth A (2008) A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol Off J Am Soc Clin Oncol 26:3785CrossRefGoogle Scholar
  3. Ashworth A, Lord CJ (2018) Synthetic lethal therapies for cancer: what’s next after PARP inhibitors? Nat Rev Clin Oncol 15:564CrossRefGoogle Scholar
  4. Bos KI, Harkins KM, Herbig A, Coscolla M, Weber N, Comas I, Forrest SA, Bryant JM, Harris SR, Schuenemann VJ, Campbell TJ, Majander K, Wilbur AK, Guichon RA, Wolfe Steadman DL, Cook DC, Niemann S, Behr MA, Zumarraga M, Bastida R, Huson D, Nieselt K, Young D, Parkhill J, Buikstra JE, Gagneux S, Stone AC, Krause J (2014) Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis. Nature 514:494CrossRefGoogle Scholar
  5. Brook CE, Dobson AP (2015) Bats as ‘special’ reservoirs for emerging zoonotic pathogens. Trends Microbiol 23:172CrossRefGoogle Scholar
  6. Chan BK, Turner PE, Kim S, Mojibian HR, Elefteriades JA, Narayan D (2018) Phage treatment of an aortic graft infected with Pseudomonas aeruginosa. Evol Med Public Health 2018:60CrossRefGoogle Scholar
  7. Coakley G, Buck AH, Maizels RM (2016) Host parasite communications—messages from helminths for the immune system Parasite communication and cell–cell interactions. Mol Biochem Parasitol 208:33CrossRefGoogle Scholar
  8. Corbett S, Courtiol A, Lummaa V, Moorad J, Stearns S (2018) The transition to modernity and chronic disease: mismatch and natural selection. Nat Rev Genet 391:1Google Scholar
  9. Crow JF (2000a) A new study challenges the current belief of a high human male:female mutation ratio. Trends Genet 16:525CrossRefGoogle Scholar
  10. Crow JF (2000b) The origins, patterns and implications of human spontaneous mutation. Nat Rev Genet 1:40CrossRefGoogle Scholar
  11. Crow JF (2012) Upsetting the dogma: germline selection in human males. PLoS Genet 8:e1002535CrossRefGoogle Scholar
  12. Cui J, Li F, Shi Z-L (2019) Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 17:181CrossRefGoogle Scholar
  13. Cunningham JJ, Brown JS, Gatenby RA, Staňková K (2018) Optimal control to develop therapeutic strategies for metastatic castrate resistant prostate cancer. J Theor Biol 459:67CrossRefGoogle Scholar
  14. D’Souza AW, Wagner GP (2014) Malignant Cancer and Invasive Placentation: a case for positive pleiotropy between endometrial and malignancy phenotypes. Evol Med Public Health 2014:136CrossRefGoogle Scholar
  15. Dudas G, Carvalho LM, Bedford T, Tatem AJ, Baele G, Faria NR, Park DJ, Ladner JT, Arias A, Asogun D, Bielejec F, Caddy SL, Cotten M, D’Ambrozio J, Dellicour S, Di Caro A, Diclaro JW, Duraffour S, Elmore MJ, Fakoli LS, Faye O, Gilbert ML, Gevao SM, Gire S, Gladden-Young A, Gnirke A, Goba A, Grant DS, Haagmans BL, Hiscox JA, Jah U, Kugelman JR, Liu D, Lu J, Malboeuf CM, Mate S, Matthews DA, Matranga CB, Meredith LW, Qu J, Quick J, Pas SD, Phan MVT, Pollakis G, Reusken CB, Sanchez-Lockhart M, Schaffner SF, Schieffelin JS, Sealfon RS, Simon-Loriere E, Smits SL, Stoecker K, Thorne L, Tobin EA, Vandi MA, Watson SJ, West K, Whitmer S, Wiley MR, Winnicki SM, Wohl S, Wölfel R, Yozwiak NL, Andersen KG, Blyden SO, Bolay F, Carroll MW, Dahn B, Diallo B, Formenty P, Fraser C, Gao GF, Garry RF, Goodfellow I, Günther S, Happi CT, Holmes EC, Kargbo B, Keita S, Kellam P, Koopmans MPG, Kuhn JH, Loman NJ, Magassouba N, Naidoo D, Nichol ST, Nyenswah T, Palacios G, Pybus OG, Sabeti PC, Sall A, Ströher U, Wurie I, Suchard MA, Lemey P, Rambaut A (2017) Virus genomes reveal factors that spread and sustained the Ebola epidemic. Nature 544:309CrossRefGoogle Scholar
  16. Ellison PT, Ottinger MA (2014) In: Weinstein M, Lane MA (eds) Sociality, hierarchy, health: comparative biodemography: papers from a workshop, pp. 315–338Google Scholar
  17. Ferretti C, Bruni L, Dangles-Marie V, Pecking AP, Bellet D (2007) Molecular circuits shared by placental and cancer cells, and their implications in the proliferative, invasive and migratory capacities of trophoblasts. Hum Reprod Update 13:121CrossRefGoogle Scholar
  18. Gagneux S (2018) Ecology and evolution of Mycobacterium tuberculosis. Nat Rev Microbiol 16:202CrossRefGoogle Scholar
  19. Gatenby R, Brown J (2018) The evolution and ecology of resistance in cancer therapy. Cold Spring Harb Perspect Med 8:a033415CrossRefGoogle Scholar
  20. Gatenby RA, Silva AS, Gillies RJ, Frieden BR (2009) Adaptive therapy. Can Res 69:4894CrossRefGoogle Scholar
  21. Gupta K, Afzal J, Maziarz JD, Hamidzadeh A, Liang C, Erkenbrack EM, Nam H, Haeger J-D, Pfarrer C, Hoang T, Ott T, Spencer T, Pavlicev M, Antczak D, Levchenko A, Wagner GP (2019) The evolution of placental invasion and cancer metastasis are causally linked. bioRxiv:1Google Scholar
  22. Hawkes K, O’Connell JF, Jones N, Alvarez H, Charnov EL (1998) Grandmothering, menopause, and the evolution of human life histories. Proc Natl Acad Sci USA 95:1336CrossRefGoogle Scholar
  23. Holmes EC, Dudas G, Rambaut A, Andersen KG (2016) The evolution of Ebola virus: insights from the 2013–2016 epidemic. Nature 538:193CrossRefGoogle Scholar
  24. Hong WS, Shpak M, Townsend JP (2015) Inferring the origin of metastases from cancer phylogenies. Can Res 75:4021CrossRefGoogle Scholar
  25. Jault P, Leclerc T, Jennes S, Pirnay JP, Que Y-A, Resch G, Rousseau AF, Ravat F, Carsin H, Le Floch R, Schaal JV, Soler C, Fevre C, Arnaud I, Bretaudeau L, Gabard J (2019) Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): a randomised, controlled, double-blind phase 1/2 trial. Lancet Infect Dis 19:35CrossRefGoogle Scholar
  26. Jennes S, Merabishvili M, Soentjens P, Pang KW, Rose T, Keersebilck E, Soete O, François P-M, Teodorescu S, Verween G, Verbeken G, De Vos D, Pirnay JP (2017) Use of bacteriophages in the treatment of colistin-only-sensitive Pseudomonas aeruginosa septicaemia in a patient with acute kidney injury—a case report. Crit Care (Lond Engl) 21:129CrossRefGoogle Scholar
  27. Kahl J, Brattig N, Liebau E (2018) The untapped pharmacopeic potential of helminths. Trends Parasitol 34:828CrossRefGoogle Scholar
  28. Kakasis A, Panitsa G (2019) Bacteriophage therapy as an alternative treatment for human infections. A comprehensive review. Int J Antimicrob Agents 53:16CrossRefGoogle Scholar
  29. Kang H-J, Feng Z, Sun Y, Atwal G, Murphy ME, Rebbeck TR, Rosenwaks Z, Levine AJ, Hu W (2009) Single-nucleotide polymorphisms in the p53 pathway regulate fertility in humans. Proc Natl Acad Sci USA 106:9761CrossRefGoogle Scholar
  30. Kerr JB, Myers M, Anderson RA (2013) The dynamics of the primordial follicle reserve. Reproduction 146:R205CrossRefGoogle Scholar
  31. Kozlowski J, Stearns SC (1989) Hypotheses for the production of excess zygotes: models of bet-hedging and selective abortion. Evolution 43:1369CrossRefGoogle Scholar
  32. Liu Z-Y, Shi W-F, Qin C-F (2019) The evolution of Zika virus from Asia to the Americas. Nat Rev Microbiol 17:131CrossRefGoogle Scholar
  33. Naxerova K, Jain RK (2015) Using tumour phylogenetics to identify the roots of metastasis in humans. Nat Rev Clin Oncol 12:258CrossRefGoogle Scholar
  34. Qiao H, Rao HBDP, Yun Y, Sandhu S, Fong JH, Sapre M, Nguyen M, Tham A, Van BW, Chng TYH, Lee A, Hunter N (2018) Impeding DNA break repair enables oocyte quality control. Mol Cell 72:211CrossRefGoogle Scholar
  35. Rook GAW (2012) Hygiene hypothesis and autoimmune diseases. Clin Rev Allergy Immunol 42:5CrossRefGoogle Scholar
  36. Sharp PM, Hahn BH (2010) The evolution of HIV-1 and the origin of AIDS. Philos Trans R Soc B 365:2487CrossRefGoogle Scholar
  37. Silva AS, Kam Y, Khin ZP, Minton SE, Gillies RJ, Gatenby RA (2012) Evolutionary approaches to prolong progression-free survival in breast cancer. Can Res 72:6362CrossRefGoogle Scholar
  38. Smith KR, Hanson HA, Buys SS (2011) Effects of BRCA1 and BRCA2 mutations on female fertility. Proc Biol Sci R Soc 279:1389CrossRefGoogle Scholar
  39. Stearns SC, Ebert D (2001) Evolution in health and disease: work in progress. Q Rev Biol 76:417CrossRefGoogle Scholar
  40. Stearns SC, Medzhitov R (2015) Evolutionary medicine. Sinauer, SunderlandGoogle Scholar
  41. Stearns SC, Govindaraju DR, Ewbank D, Byars SG (2012) Constraints on the coevolution of contemporary human males and females. Proc R Soc B 279:4836CrossRefGoogle Scholar
  42. Strassmann BI, Garrard WM (2011) Alternatives to the grandmother hypothesis. Hum Nat 22:201CrossRefGoogle Scholar
  43. Taubenberger JK, Morens DM (2006) 1918 Influenza: the mother of all pandemics. Emerg Infect Dis 12:15CrossRefGoogle Scholar
  44. Tuppi M, Kehrloesser S, Coutandin DW, Rossi V, Luh LM, Strubel A, Hoette K, Hoffmeister M, Schaefer B, De Oliveira T, Greten F, Stelzer EHK, Knapp S, De Felici M, Behrends C, Klinger FG, Doetsch V (2018) Oocyte DNA damage quality control requires consecutive interplay of CHK2 and CK1 to activate p63. Nat Struct Mol Biol 25:261CrossRefGoogle Scholar
  45. Varyani F, Fleming JO, Maizels RM (2017) Helminths in the gastrointestinal tract as modulators of immunity and pathology. Am J Physiol Gastrointest Liver Physiol 312:G537CrossRefGoogle Scholar
  46. Voskarides K (2018) Combination of 247 genome-wide association studies reveals high cancer risk as a result of evolutionary adaptation. Mol Biol Evol 35:473CrossRefGoogle Scholar
  47. Weill F-X, Domman D, Njamkepo E, Almesbahi AA, Naji M, Nasher SS, Rakesh A, Assiri AM, Sharma NC, Kariuki S, Pourshafie MR, Rauzier J, Abubakar A, Carter JY, Wamala JF, Seguin C, Bouchier C, Malliavin T, Bakhshi B, Abulmaali HHN, Kumar D, Njoroge SM, Malik MR, Kiiru J, Luquero FJ, Azman AS, Ramamurthy T, Thomson NR, Quilici M-L (2019) Genomic insights into the 2016–2017 cholera epidemic in Yemen. Nature 565:230CrossRefGoogle Scholar
  48. Worobey M, Han G-Z, Rambaut A (2014) Genesis and pathogenesis of the 1918 pandemic H1N1 influenza A virus. Proc Natl Acad Sci USA 111:201324197CrossRefGoogle Scholar
  49. Worobey M, Watts TD, McKay RA, Suchard MA, Granade T, Teuwen DE, Koblin BA, Heneine W, Lemey P, Jaffe HW (2016) 1970s and ‘Patient 0’; HIV-1 genomes illuminate early HIV/AIDS history in North America. Nature 539:98CrossRefGoogle Scholar
  50. Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, Kamiyama M, Hruban RH, Eshleman JR, Nowak MA, Velculescu VE, Kinzler KW, Vogelstein B, Iacobuzio-Donahue CA (2010) Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467:1114CrossRefGoogle Scholar
  51. Zhao Z-M, Zhao B, Bai Y, Iamarino A, Gaffney SG, Schlessinger J, Lifton RP, Rimm DL, Townsend JP (2016) Early and multiple origins of metastatic lineages within primary tumors. Proc Natl Acad Sci USA 113:2140CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Ecology and Evolutionary BiologyYale UniversityNew HavenUSA

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