Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

The ParaHox gene cluster is an evolutionary sister of the Hox gene cluster

Nature volume 392, pages 920–922 (1998)Cite this article

Abstract

Genes of the Hox cluster are restricted to the animal kingdom and play a central role in axial patterning in divergent animal phyla1. Despite its evolutionary and developmental significance, the origin of the Hox gene cluster is obscure. The consensus is that a primordial Hox cluster arose by tandem gene duplication close to animal origins2,3,4,5. Several homeobox genes with high sequence identity to Hox genes are found outside the Hox cluster and are known as ‘dispersed’ Hox-like genes; these genes may have been transposed away from an expanding cluster6. Here we show that three of these dispersed homeobox genes form a novel gene cluster in the cephalochordate amphioxus. We argue that this ‘ParaHox’ gene cluster is an ancient paralogue (evolutionary sister) of the Hox gene cluster; the two gene clusters arose by duplication of a ProtoHox gene cluster. Furthermore, we show that amphioxus ParaHox genes have co-linear developmental expression patterns in anterior, middle and posterior tissues. We propose that the origin of distinct Hox and ParaHox genes by gene-cluster duplication facilitated an increase in body complexity during the Cambrian explosion.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Homeodomains of amphioxus Cdx, Xlox and Gsx genes aligned to mouse (m), Drosophila (D), nematode (Ce), Xenopus (XI) and leech (Htr) homologues.
Figure 2: Genomic organization of amphioxus Gsx, Xlox and Cdx genes, showing genomic clones used in walking.
Figure 3: Evolutionary relationships of Cdx, Xlox and Gsx genes to Hox genes, as deduced by neighbour-joining analysis of homeodomains.
Figure 4: Origin of Hox and ParaHox gene clusters inferred from combining gene linkage and phylogenetic analyses.
Figure 5: Whole-mount in situ hybridization to 20-h amphioxus embryos.

Similar content being viewed by others

References

  1. Slack, J. M. W., Holland, P. W. H. & Graham, C. F. The zootype and the phylotypic stage. Nature 361, 490–492 (1993).

    Article  ADS  CAS  Google Scholar 

  2. Kappen, C., Schughart, K. & Ruddle, F. H. Two steps in the evolution of Antennapedia-class vertebrate homeobox genes. Proc. Natl Acad. Sci. USA 86, 5458–5463 (1989).

    Article  ADS  Google Scholar 

  3. Schubert, F. R., 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 90, 143–147 (1993).

    Article  ADS  CAS  Google Scholar 

  4. Gehring, W. J., Affolter, M. & Bürglin, T. Homeodomain proteins. Annu. Rev. Biochem. 63, 487–526 (1994).

    Article  CAS  Google Scholar 

  5. Zhang, J. & Nei, M. Evolution of Antennapedia-class homeobox genes. Genetics 142, 295–303 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Bürglin, T. in A Guidebook for Homeobox Genes (ed. Duboule, D.) 25–71 (Oxford University Press, Oxford, 1994).

    Google Scholar 

  7. Miller, D. J. & Miles, A. Homeobox genes and the zootype. Nature 365, 215–216 (1993).

    Article  ADS  CAS  Google Scholar 

  8. Candia, A. F. et al. Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. Development 116, 1123–1136 (1992).

    CAS  PubMed  Google Scholar 

  9. Garcia-Fernàndez, J. & Holland, P. W. H. Archetypal organization of the amphioxus Hox gene cluster. Nature 370, 563–566 (1994).

    Article  ADS  Google Scholar 

  10. Averof, M., Dawes, R. & Ferrier, D. Diversification of arthropod Hox genes as a paradigm for the evolution of gene functions. Sem. Cell. Dev. Biol. 7, 539–551 (1996).

    Article  CAS  Google Scholar 

  11. Williams, N. A. & Holland, P. W. H. Old head on young shoulders. Nature 383, 490 (1996).

    Article  ADS  CAS  Google Scholar 

  12. Duprey, P. et al. Amouse gene homologous to the Drosophila gene caudal is expressed in epithelial cells from the embryonic intestine. Genes Dev. 2, 1647–1654 (1988).

    Article  CAS  Google Scholar 

  13. Calleja, M., Moreno, E., Pelaz, S. & Morata, G. Visualization of gene expression in living adult Drosophila. Science 274, 252–255 (1996).

    Article  ADS  CAS  Google Scholar 

  14. Wright, C. V. E., Schnegelsberg, P. & DeRobertis, E. M. XIHbox 8—a novel Xenopus homeoprotein restricted to a narrow-band of endoderm. Development 104, 787–794 (1988).

    Google Scholar 

  15. Offield, M. F. et al. Pdx-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development 122, 983–995 (1996).

    CAS  PubMed  Google Scholar 

  16. Wysocka-Diller, J., Aisemberg, G. O. & Macagmo, E. R. Anovel homeobox cluster expressed in repeated structures of the midgut. Dev. Biol. 171, 439–447 (1995).

    Article  CAS  Google Scholar 

  17. Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. Insulin-promoter-factor-1 is required for pancreas development in mice. Nature 371, 606–609 (1994).

    Article  ADS  CAS  Google Scholar 

  18. Szucsik, J. C. et al. Altered forebrain and hindbrain development in mice mutant for the Gsh-2 homeobox gene. Dev. Biol. 191, 230–242 (1997).

    Article  CAS  Google Scholar 

  19. Li, H., Zeitler, P. S., Valerius, M. T., Small, K. & Potter, S. S. Gsh-1, an orphan Hox gene, is required for normal pituitary development. EMBO J. 15, 714–724 (1996).

    Article  CAS  Google Scholar 

  20. Gorbman, A. Early development of the hagfish pituitary gland: evidence for the endodermal origin of the adenohypophysis. Am. Zool. 23, 639–654 (1983).

    Article  Google Scholar 

  21. Gaunt, S. J., Sharpe, P. T. & Duboule, D. Spatially restricted domains of homeogene transcripts in mouse embryos: relation to a segmented body plan. Development (suppl.) 104, 169–180 (1988).

    Google Scholar 

  22. Popodi, E., Kissinger, J. C., Andrews, M. E. & Raff, R. A. Sea urchin Hox genes: insights into the ancestral Hox cluster. Mol. Biol. Evol. 13, 1078–1086 (1996).

    Article  CAS  Google Scholar 

  23. Irvine, S. Q., Warinner, S. A., Hunter, J. D. & Martindale, M. Q. Asurvey of homeobox genes in Chaetopterus variopedatus and analysis of polychaete homeodomains. Mol. Phylo. Evol. 7, 331–345 (1997).

    Article  CAS  Google Scholar 

  24. Stoffel, M. et al. Localization of human homeodomain transcription factor insulin promoter factor-1 (Ipf1) to chromosome band 13q12.1. Genomics 28, 125–126 (1995).

    Article  CAS  Google Scholar 

  25. Kozak, C. A., Goffinet, A. & Stephenson, D. A. Mouse chromosome-5. Mamm. Genome 5, s65–s78 (1994).

    CAS  PubMed  Google Scholar 

  26. Fiedorek, F. T. & Kay, E. S. Mapping of the insulin promoter factor-1 gene (Ipf1) to distal mouse chromosome-5. Genomics 28, 581–584 (1995).

    Article  CAS  Google Scholar 

  27. Conway Morris S. Why molecular biology needs palaeontology. Development (suppl.) 1–13 (1994).

  28. Lehrach, H. et al. in Genome Analysis 1: Genetic and Physical Mapping (eds Davies, K. E. & Tilghman, S.M.) 38–81 (Cold Spring Harbor Laboratory Press, New York, 1990).

    Google Scholar 

  29. Felsenstein, J. PHYLIP version 3.5c(Department of Genetics, Univ. Washington, Seattle, 1993).

  30. Holland, P. W. H., Holland, L. Z., Williams, N. A. & Holland, N. D. An amphioxus homeobox gene: sequence conservation, spatial expression during development and insights into vertebrate evolution. Development 116, 653–661 (1992).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank G. Balavoine and C. V. E. Wright for discussion, S. J. Patton and C. Burgtorf for access to the cosmid library and help with screening, and N. A. Williams and S. A. J. Thompson for advice and assistance. This research was funded by a BBSRC Earmarked Studentship (to N.M.B.) and by the DGICYT (J.G.F.), and facilitated by a grant from the Acciones Integradas of the British Council/Ministerio de Educación y Ciencia.

Author information

Authors and Affiliations

  1. School of Animal and Microbial Sciences, University of Reading, PO Box 228, Reading, Whiteknights, RG6 6AJ, UK

    Nina M. Brooke & Peter W. H. Holland

  2. Departament de Gentica, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal 645, 08028, Barcelona, Spain

    Jordi Garcia-Fernàndez

Authors
  1. Nina M. Brooke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jordi Garcia-Fernàndez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter W. H. Holland
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter W. H. Holland.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brooke, N., Garcia-Fernàndez, J. & Holland, P. The ParaHox gene cluster is an evolutionary sister of the Hox gene cluster. Nature 392, 920–922 (1998). https://doi.org/10.1038/31933

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/31933

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing