Hox Genes pp 91-100 | Cite as

Evolution of Hox Complexes

  • David E. K. Ferrier
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 689)


Recent years have seen a plethora of ideas and hypotheses, and lots of debate, about the origin and evolution of the Hox gene cluster. Here I will attempt to summarize these hypotheses, identify their strengths and weaknesses and highlight the types of new data that may lead to further resolution of the competing ideas. The major theme is that Hox genes originated very early in animal evolution and extensive independent duplications occurred in major lineages. Duplications however have not been the only route to change in the composition and structure of the Hox cluster, as extensive gene losses have occurred as well. Indeed it is gene loss that is one of the main obstacles in our understanding of the origin and evolution of Hox clusters. Matters should be improved with wider taxon sampling along with a clearer understanding of how duplicated genes evolve.


Homeobox Gene Precursor Cluster ParaHox Gene Nematostella Vectensis Amphimedon Queenslandica 
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.
    Lewis EB. Pseudoallelism and gene evolution. Cold Spring Harb Symp Quant Biol 1951; 16:159–174.PubMedGoogle Scholar
  2. 2.
    Lewis EB. Genes and developmental pathways. American Zoologist 1963; 3:33–56.Google Scholar
  3. 3.
    Lewis EB. A gene complex controlling segmentation in Drosophila. Nature 1978; 276(5688):565–570.PubMedCrossRefGoogle Scholar
  4. 4.
    McGinnis W, Garber RL, Wirz J et al. A homologous protein-coding sequence in Drosophila homeotic genes and its conservation in other metazoans. Cell 1984; 37(2):403–408.PubMedCrossRefGoogle Scholar
  5. 5.
    McGinnis W, Levine MS, Hafen E et al. A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes. Nature 1984; 308(5958):428–433.PubMedCrossRefGoogle Scholar
  6. 6.
    Takatori N, Butts T, Candiani S et al. Comprehensive survey and classification of homeobox genes in the genome of amphioxus, Branchiostoma floridae. Dev Genes Evol 2008; 218(11–12):579–590.PubMedCrossRefGoogle Scholar
  7. 7.
    Holland PWH, Booth HA, Bruford EA. Classification and nomenclature of all human homeobox genes. BMC Biol 2007; 5:47.PubMedCrossRefGoogle Scholar
  8. 8.
    Garcia-Fernàndez J. The genesis and evolution of homeobox gene clusters. Nat Rev Genet 2005; 6(12):881–892.PubMedCrossRefGoogle Scholar
  9. 9.
    Ferrier DEK. Evolution of Hox gene clusters. In: Papageorgiou S, ed. HOX gene expression. First ed. Austin, Texas, and New York: Landes Bioscience/ and Springer Science 2007; 53–67.CrossRefGoogle Scholar
  10. 10.
    Gauchat D, Mazet F, Berney C et al. Evolution of Antp-class genes and differential expression of Hydra Hox/paraHox genes in anterior patterning. Proc Natl Acad Sci USA 2000; 97(9):4493–4498.PubMedCrossRefGoogle Scholar
  11. 11.
    Larroux C, Fahey B, Degnan SM et al. The NK homeobox gene cluster predates the origin of Hox genes. Curr Biol 2007; 17(8):706–710.PubMedCrossRefGoogle Scholar
  12. 12.
    Dellaporta SL, Xu A, Sagasser S et al. Mitochondrial genome of Trichoplax adhaerens supports Placozoa as the basal lower metazoan phylum. Proc Natl Acad Sci USA 2006; 103(23):8751–8756.PubMedCrossRefGoogle Scholar
  13. 13.
    Srivastava M, Begovic E, Chapman J et al. The Trichoplax genome and the nature of placozoans. Nature 2008; 454(7207):955–960.PubMedCrossRefGoogle Scholar
  14. 14.
    Jakob W, Sagasser S, Dellaporta S et al. The Trox-2 Hox/ParaHox gene of Trichoplax (Placozoa) marks an epithelial boundary. Dev Genes Evol 2004; 214(4):170–175.PubMedCrossRefGoogle Scholar
  15. 15.
    Schierwater B, Kamm K, Srivastava M et al. The early ANTP gene repertoire: insights from the placozoan genome. PLoS ONE 2008; 3(8):e2457.PubMedCrossRefGoogle Scholar
  16. 16.
    Peterson KJ, Sperling EA. Poriferan ANTP genes: primitively simple or secondarily reduced? Evol Dev 2007; 9(5):405–408.PubMedCrossRefGoogle Scholar
  17. 17.
    Clément Y, Tavares R, Marais GA. Does lack of recombination enhance asymmetric evolution among duplicate genes? Insights from the Drosophila melanogaster genome. Gene 2006; 385:89–95.Google Scholar
  18. 18.
    Brooke NM, Garcia-Fernàndez J, Holland PWH. The ParaHox gene cluster is an evolutionary sister of the Hox gene cluster. Nature 1998; 392(6679):920–922.PubMedCrossRefGoogle Scholar
  19. 19.
    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
  20. 20.
    Ferrier DEK, Holland PWH. Ancient origin of the Hox gene cluster. Nat Rev Genet 2001; 2(1):33–38.CrossRefGoogle Scholar
  21. 21.
    . Baguña J, Riutort M. The dawn of bilaterian animals: the case of acoelomorph flatworms. Bioessays 2004; 26(10):1046–1057.PubMedCrossRefGoogle Scholar
  22. 22.
    Garcia-Fernàndez J. Hox, ParaHox, ProtoHox: facts and guesses. Heredity 2005; 94(2):145–152.PubMedCrossRefGoogle Scholar
  23. 23.
    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
  24. 24.
    Putnam NH, Srivastava M, Hellsten U et al. Sea anemone genome reveals ancestral eumetazoan gene repertoire and genomic organization. Science 2007; 317(5834):86–94.PubMedCrossRefGoogle Scholar
  25. 25.
    Larroux C, Luke GN, Koopman P et al. Genesis and expansion of metazoan transcription factor gene classes. Mol Biol Evol 2008; 25(5):980–996.PubMedCrossRefGoogle Scholar
  26. 26.
    Lanfear R, Bromham L. Statistical tests between competing hypotheses of Hox cluster evolution. Systematic Biology 2008; 57(5):708–718.PubMedCrossRefGoogle Scholar
  27. 27.
    Quiquand M, Yanze N, Schmich J et al. More constraint on ParaHox than Hox gene families in early metazoan evolution. Developmental Biology 2009; 328:173–187.PubMedCrossRefGoogle Scholar
  28. 28.
    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(1):e153.PubMedCrossRefGoogle Scholar
  29. 29.
    Kuhn K, Streit B, Schierwater B. Homeobox genes in the cnidarian Eleutheria dichotoma: evolutionary implications for the origin of Antennapedia-class (HOM/Hox) genes. Mol Phylogenet Evol 1996; 6(1):30–38.PubMedCrossRefGoogle Scholar
  30. 30.
    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
  31. 31.
    Finnerty JR, Paulson D, Burton P et al. Early evolution of a homeobox gene: the parahox gene Gsx in the Cnidaria and the Bilateria. Evol Dev 2003; 5(4):331–345.PubMedCrossRefGoogle Scholar
  32. 32.
    Hui JHL, Holland PWH, Ferrier DEK. Do cnidarians have a ParaHox cluster? Analysis of synteny around a Nematostella homeobox gene cluster. Evol Dev 2008; 10(6):725–730.PubMedCrossRefGoogle Scholar
  33. 33.
    Minguillón C, Garcia-Fernàndez J. Genesis and evolution of the Evx and Mox genes and the extended Hox and ParaHox gene clusters. Genome Biol 2003; 4(2):R12.PubMedCrossRefGoogle Scholar
  34. 34.
    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
  35. 35.
    Amemiya CT, Wagner GP. Animal evolution: when did the ‘Hox system’ arise? Curr Biol 2006; 16(14):R546–548.PubMedCrossRefGoogle Scholar
  36. 36.
    Meinhardt H. The radial-symmetric hydra and the evolution of the bilateral body plan: an old body became a young brain. Bioessays 2002; 24(2):185–191.PubMedCrossRefGoogle Scholar
  37. 37.
    Baguña J, Martinez P, Paps J et al. Back in time: a new systematic proposal for the Bilateria. Philos Trans R Soc Lond B Biol Sci 2008; 363(1496):1481–1491.PubMedCrossRefGoogle Scholar
  38. 38.
    Hejnol A, Martindale MQ. Acoel development supports a simple planula-like urbilaterian. Philos Trans R Soc Lond B Biol Sci 2008; 363(1496):1493–1501.PubMedCrossRefGoogle Scholar
  39. 39.
    Monteiro AS, Ferrier DEK. Hox genes are not always Colinear. Int J Biol Sci 2006; 2(3):95–103.PubMedGoogle Scholar
  40. 40.
    Finnerty JR, Pang K, Burton P et al. Origins of bilateral symmetry: Hox and dpp expression in a sea anemone. Science 2004; 304(5675):1335–1337.PubMedCrossRefGoogle Scholar
  41. 41.
    Jakob W, Schierwater B. Changing hydrozoan bauplans by silencing Hox-like genes. PLoS ONE 2007; 2(1):e694.PubMedCrossRefGoogle Scholar
  42. 42.
    Zhang J, Nei M. Evolution of Antennapedia-class homeobox genes. Genetics 1996; 142(1):295–303.Google Scholar
  43. 43.
    Gehring WJ, Affolter M, Bürglin T. Homeodomain proteins. Annu Rev Biochem 1994; 63:487–526.PubMedCrossRefGoogle Scholar
  44. 44.
    Schubert FR, Nieselt-Struwe K, Gruss P. The Antennapedia-type homeobox genes have evolved from three precursors separated early in metazoan evolution. Proc Natl Acad Sci USA 1993; 90(1):143–147.PubMedCrossRefGoogle Scholar
  45. 45.
    Deutsch JS, Lopez P. Are transposition events at the origin of the bilaterian Hox complexes? In: Minelli A, Fusco G, eds. Evolving Pathways: Key themes in evolutionary developmental biology. First ed. Cambridge: Cambridge University Press, 2008.Google Scholar
  46. 46.
    Akam ME, Averof M, Castelli-Gair J et al. The evolving role of Hox genes in arthropods. Dev Suppl 1994;209–215.Google Scholar
  47. 47.
    Jiménez-Guri E, Paps J, Garcia-Fernàndez J et al. Hox and ParaHox genes in Nemertodermatida, a basal bilaterian clade. Int J Dev Biol 2006; 50(8):675–679.PubMedCrossRefGoogle Scholar
  48. 48.
    Ferrier DEK, Minguillón C, Holland PWH et al. The amphioxus Hox cluster: deuterostome posterior flexibility and Hox14. Evol Dev 2000; 2(5):284–293.PubMedCrossRefGoogle Scholar
  49. 49.
    Powers TP, Amemiya CT. Evidence for a Hox14 paralog group in vertebrates. Curr Biol 2004; 14(5):R183–184.PubMedCrossRefGoogle Scholar
  50. 50.
    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
  51. 51.
    Ferrier DEK. Hox genes: Did the vertebrate ancestor have a Hox14? Curr Biol 2004; 14(5):R210–211.PubMedCrossRefGoogle Scholar
  52. 52.
    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
  53. 53.
    Meyer A, Malaga-Trillo E. Vertebrate genomics: More fishy tales about Hox genes. Curr Biol 1999; 9(6):R210–213.PubMedCrossRefGoogle Scholar
  54. 54.
    Long S, Martinez P, Chen WC et al. Evolution of echinoderms may not have required modification of the ancestral deuterostome HOX gene cluster: first report of PG4 and PG5 Hox orthologues in echinoderms. Dev Genes Evol 2003; 213(11):573–576.PubMedCrossRefGoogle Scholar
  55. 55.
    Ikuta T, Yoshida N, Satoh N et al. Ciona intestinalis Hox gene cluster: Its dispersed structure and residual colinear expression in development. Proc Natl Acad Sci USA 2004; 101(42):15118–15123.PubMedCrossRefGoogle Scholar
  56. 56.
    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
  57. 57.
    Pierce RJ, Wu W, Hirai H et al. Evidence for a dispersed Hox gene cluster in the platyhelminth parasite Schistosoma mansoni. Mol Biol Evol 2005; 22(12):2491–2503.PubMedCrossRefGoogle Scholar
  58. 58.
    Balavoine G, de Rosa R, Adoutte A. Hox clusters and bilaterian phylogeny. Mol Phylogenet Evol 2002; 24(3):366–373.PubMedCrossRefGoogle Scholar
  59. 59.
    Aboobaker AA, Blaxter ML. Hox gene loss during dynamic evolution of the nematode cluster. Curr Biol 2003; 13(1):37–40.PubMedCrossRefGoogle Scholar
  60. 60.
    Slack JM, Holland PWH, Graham CF. The zootype and the phylotypic stage. Nature 1993; 361(6412):490–492.PubMedCrossRefGoogle Scholar
  61. 61.
    King N, Westbrook MJ, Young SL et al. The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. Nature 2008; 451(7180):783–788.PubMedCrossRefGoogle Scholar
  62. 62.
    Ryan JF, Burton PM, Mazza ME et al. The cnidarian-bilaterian ancestor possessed at least 56 homeoboxes: evidence from the starlet sea anemone, Nematostella vectensis. Genome Biol 2006; 7(7):R64.PubMedCrossRefGoogle Scholar
  63. 63.
    Richards S, Gibbs RA, Weinstock GM et al. The genome of the model beetle and pest Tribolium castaneum. Nature 2008; 452(7190):949–955.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  • David E. K. Ferrier
    • 1
  1. 1.The Scottish Oceans InstituteUniversity of St AndrewsSt Andrews, FifeUK

Personalised recommendations