Biology & Philosophy

, Volume 25, Issue 4, pp 711–736 | Cite as

On the need for integrative phylogenomics, and some steps toward its creation

  • Eric BaptesteEmail author
  • Richard M. Burian


Recently improved understanding of evolutionary processes suggests that tree-based phylogenetic analyses of evolutionary change cannot adequately explain the divergent evolutionary histories of a great many genes and gene complexes. In particular, genetic diversity in the genomes of prokaryotes, phages, and plasmids cannot be fit into classic tree-like models of evolution. These findings entail the need for fundamental reform of our understanding of molecular evolution and the need to devise alternative apparatus for integrated analysis of these genomes. We advocate the development of integrative phylogenomics for analyzing these genomes and their histories, with tools suited to analyzing the importance of lateral gene transfer (LGT) and of DNA evolution in extra-cellular mobile genetic elements (e.g., viruses, plasmids). These phenomena greatly increase the complexity of relationships among interacting genetic partners, as they exchange functional genetic units. We examine the ontology of functional genetic units, interacting genetic partners, and emergent genetic associations, argue that these three categories of entities are required for a successful integrated phylogenomics. We conclude with arguments to suggest that the proposed new perspective and associated tools are suitable, and perhaps required, as a replacement for the bifurcating trees that have dominated evolutionary thinking for the last 150 years.


Lateral gene transfer Molecular evolution Tree of life Mobile genetic elements Network 



We thank the “Questioning the Tree of Life” project, sponsored by the Leverhulme Trust, for encouraging this contribution. EB thanks J. Leigh, P. Lopez, S. Halary, F.J. ‘Quick’ Lapointe and Y. Boucher for stimulating discussions; RB thanks J. Jelesko, R. Jensen, B. Mukhopadhyay, and J. Sebutal for stimulating discussions.


  1. Andersson JO, Sjogren AM, Horner DS, Murphy CA, Dyal PL, Svard SG et al (2007) A genomic survey of the fish parasite Spironucleus salmonicida indicates genomic plasticity among diplomonads and significant lateral gene transfer in eukaryote genome evolution. BMC Genomics 8:51CrossRefGoogle Scholar
  2. Bannert N, Kurth R (2004) Retroelements and the human genome: new perspectives on an old relation. Proc Natl Acad Sci USA 101(Suppl 2):14572–14579CrossRefGoogle Scholar
  3. Bapteste E, Susko E, Leigh J, MacLeod D, Charlebois RL, Doolittle WF (2005) Do orthologous gene phylogenies really support tree-thinking? BMC Evol Biol 5(1):33CrossRefGoogle Scholar
  4. Bapteste E, Susko E, Leigh J, Ruiz-Trillo I, Bucknam J, Doolittle WF (2008) Alternative methods for concatenation of core genes indicate a lack of resolution in deep nodes of the prokaryotic phylogeny. Mol Biol Evol 25(1):83–91CrossRefGoogle Scholar
  5. Bapteste E, O’Malley M, Beiko RG, Ereshefsky M, Gogarten JP et al (2009) Prokaryotic evolution and the tree of life are two different things. Biol Direct 4:34CrossRefGoogle Scholar
  6. Beatty J (1985) Speaking of Species: Darwin’s Strategy In: Kohn D (ed) Darwinian Heritage. Princeton. NJ, Princeton University Press, pp 265–282Google Scholar
  7. Beiko RG, Ragan MA (2009) Untangling hybrid phylogenetic signals: horizontal gene transfer and artifacts of phylogenetic reconstruction. Methods Mol Biol 532:241–256CrossRefGoogle Scholar
  8. Beiko RG, Doolittle WF, Charlebois RL (2008) The impact of reticulate evolution on genome phylogeny. Syst Biol 57(6):844–856CrossRefGoogle Scholar
  9. Blaiotta G, Ercolini D, Simeoli E, Moschetti G, Villani F (2000) Conditions for conjugative transposon transfer in Lactococcus lactis. Lett Appl Microbiol 31(5):343–348CrossRefGoogle Scholar
  10. Boucher Y, Bapteste E (2009) Revisiting the concept of lineage in prokaryotes: a phylogenetic perspective. BioEssays 31(5):526–536CrossRefGoogle Scholar
  11. Boucher Y, Douady CJ, Papke RT, Walsh DA, Boudreau ME et al (2003) Lateral gene transfer and the origins of prokaryotic groups. Annu Rev Genet 37:283–328CrossRefGoogle Scholar
  12. Boucher Y, Labbate M, Koenig JE, Stokes HW (2007) Integrons: mobilizable platforms that promote genetic diversity in bacteria. Trends Microbiol 15(7):301–309CrossRefGoogle Scholar
  13. Bouvier M, Demarre G, Mazel D (2005) Integron cassette insertion: a recombination process involving a folded single strand substrate. EMBO J 24(24):4356–4367CrossRefGoogle Scholar
  14. Brazelton WJ, Baross JA (2009) Abundant transposases encoded by the metagenome of a hydrothermal chimney biofilm. ISME J (Epub ahead of print)Google Scholar
  15. Brilli M, Mengoni A, Fondi M, Bazzicalupo M, Lio P, Fani R (2008) Analysis of plasmid genes by phylogenetic profiling and visualization of homology relationships using Blast2Network. BMC Bioinformatics 9:551CrossRefGoogle Scholar
  16. Brussow H (2009) The not so universal tree of life or the place of viruses in the living world. Philos Trans R Soc Lond B Biol Sci 364(1527):2263–2274CrossRefGoogle Scholar
  17. Buss LW (1987) The Evolution of individuality. Princeton University Press, PrincetonGoogle Scholar
  18. Ciccarelli F, Doerks T, von Mering C, Creevey CJ, Snel B, Bork P (2006) Toward automatic reconstruction of a highly resolved tree of life’. Science 311(5765):1283–1287CrossRefGoogle Scholar
  19. Cvitkovitch DG, Li YH, Ellen RP (2003) Quorum sensing and biofilm formation in Streptococcal infections. J Clin Invest 112(11):1626–1632Google Scholar
  20. Dagan T, Martin W (2006) The tree of one percent. Genome Biol 7:118CrossRefGoogle Scholar
  21. Dagan T, Martin W (2007) Ancestral genome sizes specify the minimum rate of lateral gene transfer during prokaryote evolution. Proc Natl Acad Sci USA 104(3):870–875CrossRefGoogle Scholar
  22. Dagan T, Martin W (2009) Getting a better picture of microbial evolution en route to a network of genomes. Philos Trans R Soc Lond B Biol Sci 364(1527):2187–2196CrossRefGoogle Scholar
  23. Dagan T, Artzy-Randrup Y, Martin W (2008) Modular networks and cumulative impact of lateral transfer in prokaryote genome evolution. Proc Natl Acad Sci USA 105(29):10039–10044CrossRefGoogle Scholar
  24. Darwin CR (1964 [1859]) On the origin of species by means of natural selection or the preservation of favoured races in the struggle for life. In: E. Mayr (ed) A facsimile of the first edition, with an introduction. Harvard University Press, CambridgeGoogle Scholar
  25. Degnan JH, Rosenberg NA (2009) Gene tree discordance, phylogenetic inference and the multispecies coalescent. Trends Ecol Evol 24(6):332–340CrossRefGoogle Scholar
  26. DeLong EF (2007) Microbiology. Life on the thermodynamic edge. Science 317(5836):327–328CrossRefGoogle Scholar
  27. Denker E, Bapteste E, Le Guyader H, Manuel M, Rabet N (2008) Horizontal gene transfer and the evolution of cnidarian stinging cells. Curr Biol 18(18):R858–R859CrossRefGoogle Scholar
  28. Doolittle WF (2009a) Eradicating typological thinking in prokaryotic systematics and evolution. In: Cold Spring Harbor symposium on quantitative biology. (Epub ahead of print)Google Scholar
  29. Doolittle WF (2009b) The practice of classification and the theory of evolution, and what the demise of Charles Darwin’s tree of life hypothesis means for both of them. Philos Trans R Soc Lond B Biol Sci 364(1527):2221–2228CrossRefGoogle Scholar
  30. Doolittle WF, Nesbo CL, Bapteste E, Zhaxybayeva O (2007) Lateral gene transfer. Evolutionary genomics and proteomics. Sinauer, SunderlandGoogle Scholar
  31. Feil EJ, Li BC, Aanensen DM, Hanage WP, Spratt BG (2004) eBURST: inferring patterns of evolutionary descent among clusters of related bacterial genotypes from multilocus sequence typing data. J Bacteriol 186(5):1518–1530CrossRefGoogle Scholar
  32. Felsenstein J (2004) Inferring phylogenies. Sinauer, SunderlandGoogle Scholar
  33. Filee J, Forterre P, Laurent J (2003) The role played by viruses in the evolution of their hosts: a view based on informational protein phylogenies. Res Microbiol 154(4):237–243CrossRefGoogle Scholar
  34. Filee J, Tetart F, Suttle CA, Krisch HM (2005) Marine T4-type bacteriophages, a ubiquitous component of the dark matter of the biosphere. Proc Natl Acad Sci USA 102(35):12471–12476CrossRefGoogle Scholar
  35. Forterre P (2010) Defining life: the virus viewpoint. Orig Life Evol Biosph 40(2):151–160CrossRefGoogle Scholar
  36. Fraser C, Hanage WP, Spratt BG (2007) Recombination and the nature of bacterial speciation. Science 315(5811):476–480CrossRefGoogle Scholar
  37. Frost LS, Leplae R, Summers AO, Toussaint A (2005) Mobile genetic elements: the agents of open source evolution. Nat Rev Microbiol 3(9):722–732CrossRefGoogle Scholar
  38. Galtier N, Daubin V (2008) Dealing with incongruence in phylogenomic analyses. Philos Trans R Soc Lond B Biol Sci 363(1512):4023–4029CrossRefGoogle Scholar
  39. Ghigo JM (2001) Natural conjugative plasmids induce bacterial biofilm development. Nature 412(6845):442–445CrossRefGoogle Scholar
  40. Halary S, Leigh JW, Cheaib B, Lopez P, Bapteste E (2010) Network analyses structure genetic diversity in independent genetic worlds. Proc Natl Acad Sci USA 107(1):127–132CrossRefGoogle Scholar
  41. Hanage WP, Fraser C, Spratt BG (2006) The impact of homologous recombination on the generation of diversity in bacteria. J Theor Biol 239(2):210–219CrossRefGoogle Scholar
  42. Hatfull GF, Cresawn SG, Hendrix RW (2008) Comparative genomics of the mycobacteriophages: insights into bacteriophage evolution. Res Microbiol 159(5):332–339CrossRefGoogle Scholar
  43. Hendrix RW, Smith MC, Burns RN, Ford ME, Hatfull GF (1999) Evolutionary relationships among diverse bacteriophages and prophages all the world’s a phage. Proc Natl Acad Sci USA 96(5):2192–2197CrossRefGoogle Scholar
  44. Hennig W (1966) Phylogenetic systematics. University of Illinois Press, UrbanaGoogle Scholar
  45. Horike T, Hamada K, Shinozawa T (2002) Origin of eukaryotic cell nuclei by symbiosis of Archaea in bacteria supported by the newly clarified origin of functional genes. Genes Genet Syst 77(5):369–376CrossRefGoogle Scholar
  46. Jefferson KK (2004) What drives bacteria to produce a biofilm? FEMS Microbiol Lett 236(2):163–173Google Scholar
  47. Junker BH, Koschutzki D, Schreiber F (2006) Exploration of biological network centralities with CentiBiN. BMC Bioinformatics 7:219CrossRefGoogle Scholar
  48. Killcoyne S, Carter GW, Smith J, Boyle J (2009) Cytoscape: a community-based framework for network modeling. Methods Mol Biol 563:219–239CrossRefGoogle Scholar
  49. Klieve AV, Yokoyama MT, Forster RJ, Ouwerkerk D, Bain PA, Mawhinney EL (2005) Naturally occurring DNA transfer system associated with membrane vesicles in cellulolytic Ruminococcus spp. of ruminal origin. Appl Environ Microbiol 71(8):4248–4253CrossRefGoogle Scholar
  50. Koonin EV (2009) Darwinian evolution in the light of genomics. Nucleic Acids Res 37(4):1011–1034CrossRefGoogle Scholar
  51. Koonin EV, Wolf YI, Puigbo P (2009) The phylogenetic forest and the quest for the elusive tree of life. Cold Spring Harbor symposium on quantitative biology. (Epub ahead of print)Google Scholar
  52. Lakatos I (1970) Falsification and the methodology of scientific research programmes. In: Lakatos I, Musgrave A (eds) Criticism and the growth of knowledge. Cambridge University Press, Cambridge, pp 91–230Google Scholar
  53. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921CrossRefGoogle Scholar
  54. Lane CE, Archibald JM (2008) The eukaryotic tree of life: endosymbiosis takes its TOL Trends. Ecol Evol 23(5):268–275CrossRefGoogle Scholar
  55. Lapointe FJ, Lopez P, Boucher Y, Koenig J, Bapteste E (2010) Clanistics: a multi-level perspective for harvesting unrooted gene trees. Trends Micro (in press)Google Scholar
  56. Li N, Cannon MC (1998) Gas vesicle genes identified in Bacillus megaterium and functional expression in Escherichia coli. J Bacteriol 180(9):2450–2458Google Scholar
  57. Lima-Mendez G, Van Helden J, Toussaint A, Leplae R (2008) Reticulate representation of evolutionary and functional relationships between phage genomes. Mol Biol Evol 25(4):762–777CrossRefGoogle Scholar
  58. Lindell D, Jaffe JD, Johnson ZI, Church GM, Chisholm SW (2005) Photosynthesis genes in marine viruses yield proteins during host infection. Nature 438(7064):86–89CrossRefGoogle Scholar
  59. Loftus B, Anderson I, Davies R, Alsmark UC, Samuelson J, Amedeo P et al (2005) The genome of the protist parasite Entamoeba histolytica. Nature 433(7028):865–868CrossRefGoogle Scholar
  60. Loo CY, Corliss DA, Ganeshkumar N (2000) Streptococcus gordonii biofilm formation: identification of genes that code for biofilm phenotypes. J Bacteriol 182(5):1374–1382CrossRefGoogle Scholar
  61. Lopez P, Bapteste E (2009) Molecular phylogeny: reconstructing the forest. C R Biol 332(2–3):171–182CrossRefGoogle Scholar
  62. Mallet J (2010) Why was Darwin’s view of species rejected by 20th century biologists? Biol Phil (this issue)Google Scholar
  63. Marri PR, Hao W, Golding GB (2007) The role of laterally transferred genes in adaptive evolution. BMC Evol Biol 7(Suppl 1):S8CrossRefGoogle Scholar
  64. Martin W, Embley TM (2004) Evolutionary biology: early evolution comes full circle. Nature 431(7005):134–137CrossRefGoogle Scholar
  65. Mayr E (1964) From molecules to organic diversity. Fed Proc 23:1231–1235Google Scholar
  66. Mayr E (1968) The role of systematics in biology. Science 159(815):595–599CrossRefGoogle Scholar
  67. Mitreva M, Blaxter ML, Bird DM, McCarter JP (2005) Comparative genomics of nematodes. Trends Genet 21(10):573–581CrossRefGoogle Scholar
  68. Norman A, Hansen LH, Sorensen SJ (2009) Conjugative plasmids: vessels of the communal gene pool. Philos Trans R Soc Lond B Biol Sci 364(1527):2275–2289CrossRefGoogle Scholar
  69. Nystedt B, Frank AC, Thollesson M, Andersson SG (2008) Diversifying selection and concerted evolution of a type IV secretion system in Bartonella. Mol Biol Evol 25(2):287–300CrossRefGoogle Scholar
  70. O’Hara RJ (1997) Population thinking and tree thinking in systematics. Zool Scr 26(4):323–329CrossRefGoogle Scholar
  71. Pedulla ML, Ford ME, Houtz JM, Karthikeyan T, Wadsworth C, Lewis JA et al (2003) Origins of highly mosaic mycobacteriophage genomes. Cell 113(2):171–182CrossRefGoogle Scholar
  72. Perez-Losada M, Browne EB, Madsen A, Wirth T, Viscidi RP, Crandall KA (2006) Population genetics of microbial pathogens estimated from multilocus sequence typing (MLST) dat. Infect Genet Evol 6(2):97–112CrossRefGoogle Scholar
  73. Ragan MA, McInerney JO, Lake JA (2009) The network of life: genome beginnings and evolution. Introduction. Philos Trans R Soc Lond B Biol Sci 364(1527):2169–2175CrossRefGoogle Scholar
  74. Roberts AP, Cheah G, Ready D, Pratten J, Wilson M, Mullany P (2001) Transfer of TN916-like elements in microcosm dental plaques. Antimicrob Agents Chemother 45(10):2943–2946CrossRefGoogle Scholar
  75. Rohwer F, Thurber RV (2009) Viruses manipulate the marine environment. Nature 459(7244):207–212CrossRefGoogle Scholar
  76. Rosenberg NA, Nordborg M (2002) Genealogical trees, coalescent theory and the analysis of genetic polymorphisms. Nat Rev Genet 3(5):380–390CrossRefGoogle Scholar
  77. Sharma AK, Walsh DA, Bapteste E, Rodriguez-Valera F, Doolittle WF, Papke RT (2007) Evolution of rhodopsin ion pumps in haloarchaea. BMC Evol Biol 18(7):79CrossRefGoogle Scholar
  78. Shi T, Falkowski PG (2008) Genome evolution in cyanobacteria: the stable core and the variable shell. Proc Natl Acad Sci USA 105(7):2510–2515CrossRefGoogle Scholar
  79. Sneath RR, Sokal PHA (1973) Numerical Taxonomy. W.H. Freeman, San FranciscoGoogle Scholar
  80. Susko E, Leigh J, Doolittle WF, Bapteste E (2006) Visualizing and assessing phylogenetic congruence of core gene sets: a case study of the gamma-proteobacteria. Mol Biol Evol 23(5):1019–1030CrossRefGoogle Scholar
  81. Touchon M, Hoede C, Tenaillon O, Barbe V, Baeriswyl S, Bidet P et al (2009) Organised genome dynamics in the Escherichia coli species results in highly diverse adaptive paths. PLoS Genet 5(1):e1000344CrossRefGoogle Scholar
  82. Van Melderen L, Saavedra De Bast M (2009) Bacterial toxin-antitoxin systems: more than selfish entities? PLoS Genet 5(3):e1000437CrossRefGoogle Scholar
  83. Villarreal LP, Witzany G (2009) Viruses are essential agents within the roots and stem of the tree of life. J TheorBiol (Epub ahead of print)Google Scholar
  84. Wagner GP, Altenberg L (1996) Complex adaptations and the evolution of evolvability. Evolution 50(3):967–976CrossRefGoogle Scholar
  85. Welch RA, Burland V, Plunkett G 3rd, Redford P, Roesch P, Rasko D et al (2002) Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc Natl Acad Sci USA 99(26):17020–17024CrossRefGoogle Scholar
  86. Wilkinson M, McInerney JO, Hirt RP, Foster PG, Embley TM (2007) Of clades and clans: terms for phylogenetic relationships in unrooted trees. Trends Ecol Evol 22(3):114–115CrossRefGoogle Scholar
  87. Woese CR, Kandler O, Wheelis ML (1990) ‘Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya. Proc Natl Acad Sci USA 87(12):4576–4579CrossRefGoogle Scholar
  88. Xiang X, Chen L, Huang X, Luo Y, She Q, Huang L (2005) Sulfolobus tengchongensis spindle-shaped virus STSV1: virus-host interactions and genomic features. J Virol 79(14):8677–8686CrossRefGoogle Scholar
  89. Zhao Y, Wang K, Budinoff C, Buchan A, Lang A, Jiao N, Chen F (2009) Gene transfer agent (GTA) genes reveal diverse and dynamic Roseobacter and Rhodobacter populations in the Chesapeake Bay. ISME J 3(3):364–373CrossRefGoogle Scholar
  90. Zhaxybayeva O, Gogarten JP, Charlebois RL, Doolittle WF, Papke RT (2006) Phylogenetic analyses of cyanobacterial genomes: quantification of horizontal gene transfer events. Genome Res 16(9):1099–1108CrossRefGoogle Scholar
  91. Zuckerkandl E, Pauling L (1965) Molecules as documents of evolutionary history. J Theor Biol 8(2):357–366CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.UMR CNRS 7138UPMCParisFrance
  2. 2.Department of Philosophy – 0126Virginia TechBlacksburgUSA

Personalised recommendations