Hox Genes pp 111-122 | Cite as

Are the Deuterostome Posterior Hox Genes a Fast-Evolving Class?

  • Robert Lanfear
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 689)


There has been a great deal of interest in analysing the molecular evolution of the Hox cluster using both bioinformatic and experimental approaches. The posterior Hox genes have been of particular interest to both groups of biologists for a number of reasons: they appear to be associated with the evolution of a number of morphological novelties; the protostomes appear to be have lost a highly-conserved and functionally important amino acid motif (the hexapeptide motif ) from their posterior Hox genes; and deuterostome posterior Hox genes seem to be evolving more quickly than all other Hox genes. In this chapter I will discuss the last of these points.

The idea that Deuterostome posterior Hox genes were evolving more quickly than other Hox genes was first suggested by David Ferrier and colleagues.1 In this chapter, I start by introducing the posterior Hox genes—their distribution among the animal phyla and the likely sequence of duplications that led to this distribution. I then introduce the idea of ‘deuterostome posterior flexibility’1 and examine this hypothesis in light of more recent phylogenetic and genomic work on the Hox cluster. Finally, I discuss some new approaches that could be used to test directly for differential rates of evolution among Hox genes and to assess what might underlie these differences.


Gene Duplication Phylogenetic Resolution ParaHox Gene Nematostella Vectensis Phylogenetic Support 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ferrier DEK, Minguillon C, Holland PWH et al. The amphioxus hox cluster: deuterostome posterior flexibility and hox14. Evol Dev 2000; 2(5):284–293.PubMedCrossRefGoogle Scholar
  2. 2.
    Peterson KJ, Butterfield NJ. Origin of the eumetazoa: testing ecological predictions of molecular clocks against the proterozoic fossil record. Proc Natl Acad Sci USA 2005; 102(27):9547–9552.PubMedCrossRefGoogle Scholar
  3. 3.
    Aguinaldo AM, Turbeville JM, Linford LS et al. Evidence for a clade of nematodes, arthropods and other moulting animals. Nature 1997; 387(6632):489–493.PubMedCrossRefGoogle Scholar
  4. 4.
    Balavoine G, de Rosa R, Adoutte A. Hox clusters and bilaterian phylogeny. Mol Phylogenet Evol 2002; 24(3):366–373.PubMedCrossRefGoogle Scholar
  5. 5.
    Cook CE, Jimenez E, Akam M et al. The hox gene complement of acoel flatworms, a basal bilaterian clade. Evol Dev 2004; 6(3):154–163.PubMedCrossRefGoogle Scholar
  6. 6.
    Ryan JF, Mazza ME, Pang K et al. Pre-bilaterian origins of the hox cluster and the hox code: evidence from the sea anemone, nematostella vectensis. PLoS One 2007; 2:e153.CrossRefGoogle Scholar
  7. 7.
    Kamm K, Schierwater B, Jakob W et al. Axial patterning and diversification in the cnidaria predate the hox system. Curr Biol 2006; 16(9):920–926.PubMedCrossRefGoogle Scholar
  8. 8.
    Finnerty JR, Martindale MQ. Ancient origins of axial patterning genes: hox genes and ParaHox genes in the cnidaria. Evol Dev 1999; 1(1):16–23.PubMedCrossRefGoogle Scholar
  9. 9.
    Finnerty JR, Martindale MQ. Homeoboxes in sea anemones (cnidaria; anthozoa): a PCR-based survey of nematostella vectensis and metridium senile. Biol Bull 1997; 193(1):62–76.PubMedCrossRefGoogle Scholar
  10. 10.
    Ferrier DEK, Holland PWH. Ancient origin of the hox gene cluster. Nat Rev Gen 2001; 2(1):33–38.CrossRefGoogle Scholar
  11. 11.
    Cameron RA, Rowen L, Nesbitt R et al. Unusual gene order and organization of the sea urchin hox cluster. J Exp Zoolog B Mol Dev Evol 2006; 306(1):45–58.CrossRefGoogle Scholar
  12. 12.
    de Rosa R, Grenier JK, Andreeva T et al. Hox genes in brachiopods and priapulids and protostome evolution. Nature 1999; 399(6738):772–776.PubMedCrossRefGoogle Scholar
  13. 13.
    Matus D, Halanych KM, Martindale MQ. The hox gene complement of a pelagic chaetognath, flaccisagitta enflata. Integ Comp Biol 2007; 47:854–864.CrossRefGoogle Scholar
  14. 14.
    Peterson KJ. Isolation of hox and parahox genes in the hemichordate ptychodera flava and the evolution of deuterostome hox genes. Mol Phylogenet Evol 2004; 31(3):1208–1215.PubMedCrossRefGoogle Scholar
  15. 15.
    Aronowicz J, Lowe CJ. Hox gene expression in the hemichordate saccoglossus kowalevskii and the evolution of deuterostome nervous systems. Integ Comp Biol 2006; 46:890–901.CrossRefGoogle Scholar
  16. 16.
    Kmita-Cunisse M, Loosli F, Bierne J et al. Homeobox genes in the ribbonworm lineus sanguineus: evolutionary implications. Proc Natl Acad Sci USA 1998; 95(6):3030–3035.PubMedCrossRefGoogle Scholar
  17. 17.
    Nogi T, Watanabe K. Position-specific and noncolinear expression of the planarian posterior (abdominal-B-like) gene. Dev Growth Differ 2001; 43(2):177–184.PubMedCrossRefGoogle Scholar
  18. 18.
    Callaerts P, Lee PN, Hartmann B et al. HOX genes in the sepiolid squid euprymna scolopes: implications for the evolution of complex body plans. Proc Natl Acad Sci USA 2002; 99(4):2088–2093.PubMedCrossRefGoogle Scholar
  19. 19.
    Akam M. Hox and HOM: homologous gene clusters in insects and vertebrates. Cell 1989; 57(3):347–349.PubMedCrossRefGoogle Scholar
  20. 20.
    Grenier JK, Garber TL, Warren R et al. Evolution of the entire arthropod hox gene set predated the origin and radiation of the onychophoran/arthropod clade. Curr Biol 1997; 7(8):547–553.PubMedCrossRefGoogle Scholar
  21. 21.
    Van Auken K, Weaver DC, Edgar LG et al. Caenorhabditis elegans embryonic axial patterning requires two recently discovered posterior-group hox genes. Proc Natl Acad Sci USA 2000; 97(9):4499–4503.PubMedCrossRefGoogle Scholar
  22. 22.
    Holland LZ, Albalat R, Azumi K et al. The amphioxus genome illuminates vertebrate origins and cephalochordate biology. Genome Res 2008; 18(7):1100–1111.PubMedCrossRefGoogle Scholar
  23. 23.
    Seo HC, Edvardsen RB, Maeland AD et al. Hox cluster disintegration with persistent anteroposterior order of expression in oikopleura dioica. Nature 2004; 431(7004):67–71.PubMedCrossRefGoogle Scholar
  24. 24.
    Duboule D, Boncinelli E, DeRobertis E et al. An update of mouse and human HOX gene nomenclature. Genomics 1990; 7(3):458–459.PubMedCrossRefGoogle Scholar
  25. 25.
    Fritzsch G, Bohme MU, Thorndyke M et al. PCR survey of xenoturbella bocki hox genes. J Exp Zoolog B Mol Dev Evol 2008; 310(3):278–284.CrossRefGoogle Scholar
  26. 26.
    Papillon D, Perez Y, Fasano L et al. Hox gene survey in the chaetognath spadella cephaloptera: evolutionary implications. Dev Genes Evol 2003; 213(3):142–148.PubMedGoogle Scholar
  27. 27.
    Aboobaker A. Hox gene evolution in nematodes: novelty conserved. Curr Opin Genet Dev 2003; 13(6):593–598.PubMedCrossRefGoogle Scholar
  28. 28.
    Aboobaker AA, Blaxter ML. Hox gene loss during dynamic evolution of the nematode cluster. Curr Biol 2003; 13(1):37–40.PubMedCrossRefGoogle Scholar
  29. 29.
    Wang BB, Muller-Immergluck MM, Austin J et al. A homeotic gene cluster patterns the anteroposterior body axis of C. elegans. Cell 1993; 74(1):29–42.PubMedCrossRefGoogle Scholar
  30. 30.
    Ferrier DEK. Evolution of hox gene clusters. In: Papageorgiou S, ed. Hox Gene Expression. New York: Springer, 2007:53–67.CrossRefGoogle Scholar
  31. 31.
    Amemiya CT, Prohaska SJ, Hill-Force A et al. The amphioxus hox cluster: characterization, comparative genomics and evolution. J Exp Zoolog B Mol Dev Evol 2008; 310(5):465–477.CrossRefGoogle Scholar
  32. 32.
    Minguillon C, Gardenyes J, Serra E et al. No more than 14: the end of the amphioxus hox cluster. Int J Biol Sci 2005; 1(1):19–23.PubMedGoogle Scholar
  33. 33.
    Swalla BJ, Smith AB. Deciphering deuterostome phylogeny: molecular, morphological and palaeontological perspectives. Philos Trans R Soc Lond B Biol Sci 2008; 363(1496):1557–1568.PubMedCrossRefGoogle Scholar
  34. 34.
    Lemons D, McGinnis W. Genomic evolution of hox gene clusters. Science 2006; 313(5795):1918–1922.PubMedCrossRefGoogle Scholar
  35. 35.
    Amores A, Force A, Yan YL et al. Zebrafish hox clusters and vertebrate genome evolution. Science 1998; 282(5394):1711–1714.PubMedCrossRefGoogle Scholar
  36. 36.
    Chourrout D, Delsuc F, Chourrout P et al. Minimal ProtoHox cluster inferred from bilaterian and cnidarian hox complements. Nature 2006; 442(7103):684–687.PubMedCrossRefGoogle Scholar
  37. 37.
    Ferrier DE. Hox genes: did the vertebrate ancestor have a Hox14? Curr Biol 2004; 14(5):R210–211.PubMedCrossRefGoogle Scholar
  38. 38.
    Finnerty JR, Martindale MQ. The evolution of the hox cluster: insights from outgroups. Curr Opin Genet Dev 1998; 8(6):681–687.PubMedCrossRefGoogle Scholar
  39. 39.
    Garcia-Fernandez J. Hox, ParaHox, ProtoHox: facts and guesses. Heredity 2005; 94(2):145–152.PubMedCrossRefGoogle Scholar
  40. 40.
    Kourakis MJ, Martindale MQ. Combined-method phylogenetic analysis of hox and paraHox genes of the metazoa. J Exp Zool 2000; 288(2):175–191.PubMedCrossRefGoogle Scholar
  41. 41.
    Ogishima S, Tanaka H. Missing link in the evolution of hox clusters. Gene 2007; 387(1–2):21–30.PubMedCrossRefGoogle Scholar
  42. 42.
    Powers TP, Amemiya CT. Evidence for a hox14 paralog group in vertebrates. Curr Biol 2004; 14(5):R183–184.PubMedCrossRefGoogle Scholar
  43. 43.
    Kuraku S, Takio Y, Tamura K et al. Noncanonical role of hox14 revealed by its expression patterns in lamprey and shark. Proc Natl Acad Sci USA 2008; 105(18):6679–6683.PubMedCrossRefGoogle Scholar
  44. 44.
    Lanfear R, Bromham L. Statistical tests between competing hypotheses of hox cluster evolution. Syst Biol 2008; 57(5):1–11.CrossRefGoogle Scholar
  45. 45.
    Schubert M, Escriva H, Xavier-Neto J et al. Amphioxus and tunicates as evolutionary model systems. Trends Ecol Evol 2006; 21(5):269–277.PubMedCrossRefGoogle Scholar
  46. 46.
    Peterson KJ, McPeek MA, Evans DAD. Tempo and mode of early animal evolution: inferences from rocks, hox and molecular clocks. Paleobiology 2005; 31(2):36–55.CrossRefGoogle Scholar
  47. 47.
    Pascual-Anaya J, D’Aniello S, Garcia-Fernandez J. Unexpectedly large number of conserved noncoding regions within the ancestral chordate hox cluster. Dev Genes Evol 2008; 218(11–12):591–7. Epub 2008 Sep 13.PubMedCrossRefGoogle Scholar
  48. 48.
    Santini S, Boore JL, Meyer A. Evolutionary conservation of regulatory elements in vertebrate hox gene clusters. Genome Res 2003; 13(6A):1111–1122.PubMedCrossRefGoogle Scholar
  49. 49.
    Prince VE, Pickett FB. Splitting pairs: the diverging fates of duplicated genes. Nat Rev Genet 2002; 3(11):827–837.PubMedCrossRefGoogle Scholar
  50. 50.
    Mazet F, Shimeld SM. Gene duplication and divergence in the early evolution of vertebrates. Curr Opin Genet Dev 2002; 12(4):393–396.PubMedCrossRefGoogle Scholar
  51. 51.
    Lynch M, Conery JS. The evolutionary fate and consequences of duplicate genes. Science 2000; 290(5494):1151–1155.PubMedCrossRefGoogle Scholar
  52. 52.
    Force A, Lynch M, Pickett FB et al. Preservation of duplicate genes by complementary, degenerative mutations. Genetics 1999; 151(4):1531–1545.PubMedGoogle Scholar
  53. 53.
    Kondrashov FA, Rogozin IB, Wolf YI et al. Selection in the evolution of gene duplications. Genome Biol 2002; 3(2):RESEARCH0008.Google Scholar
  54. 54.
    Kondrashov FA, Kondrashov AS. Role of selection in fixation of gene duplications. J Theor Biol 2006; 239(2):141–151.PubMedCrossRefGoogle Scholar
  55. 55.
    Van de Peer Y, Taylor JS, Braasch I et al. The ghost of selection past: rates of evolution and functional divergence of anciently duplicated genes. J Mol Evol 2001; 53(4–5):436–446.PubMedCrossRefGoogle Scholar
  56. 56.
    Taylor JS, Raes J. Duplication and divergence: the evolution of new genes and old ideas. Annu Rev Genet 2004; 38:615–643.PubMedCrossRefGoogle Scholar
  57. 57.
    Lynch VJ, Roth JJ, Wagner GP. Adaptive evolution of hox-gene homeodomains after cluster duplications. BMC Evol Biol 2006; 6:86.PubMedCrossRefGoogle Scholar
  58. 58.
    McClintock JM, Carlson R, Mann DM et al. Consequences of hox gene duplication in the vertebrates: an investigation of the zebrafish hox paralogue group 1 genes. Development 2001; 128(13):2471–2484.PubMedGoogle Scholar
  59. 59.
    Holland PWH, GarciaFernandez J. Hox genes and chordate evolution. Dev Biol 1996; 173(2):382–395.PubMedCrossRefGoogle Scholar
  60. 60.
    Wagner GP, Amemiya C, Ruddle F. Hox cluster duplications and the opportunity for evolutionary novelties. Proc Natl Acad Sci USA 2003; 100(25):14603–14606.PubMedCrossRefGoogle Scholar
  61. 61.
    Budd GE. Does evolution in body patterning genes drive morphological change—or vice versa? Bioessays 1999; 21(4):326–332.CrossRefGoogle Scholar
  62. 62.
    Hughes CL, Kaufman TC. Hox genes and the evolution of the arthropod body plan. Evol Dev 2002; 4(6):459–499.PubMedCrossRefGoogle Scholar
  63. 63.
    Gellon G, McGinnis W. Shaping animal body plans in development and evolution by modulation of hox expression patterns. Bioessays 1998; 20(2):116–125.PubMedCrossRefGoogle Scholar
  64. 64.
    Burke AC, Nelson CE, Morgan BA et al. Hox genes and the evolution of vertebrate axial morphology. Development 1995; 121(2):333–346.PubMedGoogle Scholar
  65. 65.
    Zakany J, Duboule D. The role of hox genes during vertebrate limb development. Curr Opin Genet Dev 2007; 17(4):359–366.PubMedCrossRefGoogle Scholar
  66. 66.
    Zakany J, Kmita M, Duboule D. A dual role for hox genes in limb anterior-posterior asymmetry. Science 2004; 304(5677):1669–1672.PubMedCrossRefGoogle Scholar
  67. 67.
    Davis AP, Witte DP, Hsieh-Li HM et al. Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11. Nature 1995; 375(6534):791–795.PubMedCrossRefGoogle Scholar
  68. 68.
    Deschamps J. Developmental biology. Hox genes in the limb: a play in two acts. Science 2004; 304(5677):1610–1611.PubMedCrossRefGoogle Scholar
  69. 69.
    Galis F, Kundrat M, Metz JA. Hox genes, digit identities and the theropod/bird transition. J Exp Zoolog B Mol Dev Evol 2005; 304(3):198–205.CrossRefGoogle Scholar
  70. 70.
    Gerhart J, Lowe C, Kirschner M. Hemichordates and the origin of chordates. Curr Opin Genet Dev 2005; 15(4):461–467.PubMedCrossRefGoogle Scholar
  71. 71.
    Smith AB. Deuterostomes in a twist: the origins of a radical new body plan. Evol Dev 2008; 10(4):493–503.PubMedCrossRefGoogle Scholar
  72. 72.
    Shen WF, Montgomery JC, Rozenfeld S et al. AbdB-like hox proteins stabilize DNA binding by the Meis1 homeodomain proteins. Mol Cell Biol 1997; 17(11):6448–6458.PubMedGoogle Scholar
  73. 73.
    Campos PR, de Oliveira VM, Wagner GP et al. Gene phylogenies and protein-protein interactions: possible artifacts resulting from shared protein interaction partners. J Theor Biol 2004; 231(2):197–202.PubMedCrossRefGoogle Scholar
  74. 74.
    Welch JJ, Waxman D. Calculating independent contrasts for the comparative study of substitution rates. J Theor Biol 2008; 251(4):667–678.PubMedCrossRefGoogle Scholar
  75. 75.
    Pagel M, Venditti C, Meade A. Large punctuational contribution of speciation to evolutionary divergence at the molecular level. Science 2006; 314(5796):119–121.PubMedCrossRefGoogle Scholar
  76. 76.
    Xiang QY, Zhang WH, Ricklefs RE et al. Regional differences in rates of plant speciation and molecular evolution: a comparison between eastern Asia and eastern North America. Evolution 2004; 58(10):2175–2184.PubMedGoogle Scholar
  77. 77.
    Bromham L, Woolfit M, Lee MS et al. Testing the relationship between morphological and molecular rates of change along phylogenies. Evolution Int J Org Evolution 2002; 56(10):1921–1930.Google Scholar
  78. 78.
    Davies TJ, Savolainen V. Neutral theory, phylogenies and the relationship between phenotypic change and evolutionary rates. Evolution Int J Org Evolution 2006; 60(3):476–483.Google Scholar
  79. 79.
    Goh CS, Bogan AA, Joachimiak M et al. Co-evolution of proteins with their interaction partners. J Mol Biol 2000; 299(2):283–293.PubMedCrossRefGoogle Scholar
  80. 80.
    Chiu CH, Amemiya C, Dewar K et al. Molecular evolution of the HoxA cluster in the three major gnathostome lineages. Proc Natl Acad Sci USA 2002; 99(8):5492–5497.PubMedCrossRefGoogle Scholar
  81. 81.
    Chiu CH, Dewar K, Wagner GP et al. Bichir HoxA cluster sequence reveals surprising trends in ray-finned fish genomic evolution. Genome Res 2004; 14(1):11–17.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  • Robert Lanfear
    • 1
  1. 1.Centre for Macroevolution and Macroecology, School of Botany and ZoologyAustralian National UniversityCanberraAustralia

Personalised recommendations