Development Genes and Evolution

, Volume 217, Issue 11–12, pp 801–806 | Cite as

Early diversification and complex evolutionary history of the p53 tumor suppressor gene family

Sequence Corner

Abstract

The p53 tumor suppressor plays the leading role in malignancy and in maintaining the genome’s integrity and stability. p53 belongs to a gene family that in vertebrates includes two additional members, p63 and p73. Although similar in sequence, gene structure, and expression potential, the three p53 members differ in domain organization (in addition to the transactivation, DNA-binding, and tetramerization domains, p63 and p73 encode a sterile alpha motif, SAM, domain) and functional roles (with p63 and p73 assuming additional key roles in development). It is interesting to note that outside vertebrates, p53-like sequences have only been found as single genes, of either the p53 or the p63/p73 type (i.e., without or with a SAM domain, respectively). In this paper, we report that the diversification of this family is not restricted to the vertebrate lineage, as both a p53- and a p63/p73-type sequence are present in the unicellular choanoflagellate, Monosiga brevicollis. Furthermore, multiple independent duplication events involving p53-type sequences took place in several other animal lineages (cnidarians, flat worms, insects). These findings argue that selective factors other than those associated with the evolution of vertebrates are also relevant to the diversification of this family. Understanding the selective pressures associated with the multiple independent duplication events that took place in the p53 family and the roles of p53-like proteins outside vertebrates will provide further insight into the evolution of this very important family. In addition, the presence of both a p53 and a p63/73 copy in the unicellular M. brevicollis argues for its suitability as a model system for elucidating the functions of the p53 members and the mechanisms associated with their functional diversification.

Keywords

Tumor suppressor p53 gene family Monosiga brevicollis Evolution Gene duplication 

Notes

Acknowledgments

This research was supported by a Discovery Grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to A.M.N. Many of the sequences analyzed in this study were produced by the Joint Genome Institute (http://www.jgi.doe.gov/; Lottia, Capitella, Monosiga, Nematostella, Ciona, Branchiostoma, Xenopus), the Human Genome Sequencing Center at Baylor College of Medicine (http://www.hgsc.bcm.tmc.edu/projects/; Tribolium), and The Wellcome Trust Sanger Institute (http://www.sanger.ac.uk/; Schistosoma).

Supplementary material

427_2007_185_MOESM1_ESM.doc (850 kb)
ESM 1 (DOC 870 kb)

References

  1. Cox RL, Stephens RE, Reinisch CL (2003) p63/73 homologues in surf clam: novel signaling motifs and implications for control of expression. Gene 320:49–58PubMedCrossRefGoogle Scholar
  2. D’Erchia AM, Tullo A, Pesole G, Saccone C, Sbisa E (2003) p53 gene family: Structural, Functional and Evolutionary Features. Current Genomics 4:13–26CrossRefGoogle Scholar
  3. De Laurenzi V, Melino G (2000) Evolution of functions within the p53/p63/p73 family. Ann NY Acad Sci 926:90–100PubMedCrossRefGoogle Scholar
  4. Hayat M, Howlader N, Reichman ME, Edwards BK (2007) Cancer statistics, trends, and multiple primary cancer analyses from the surveillance, epidemiology, and end results (SEER) program. Oncologist 12:20–37PubMedCrossRefGoogle Scholar
  5. Helton ES, Chen XB (2007) p53 modulation of the DNA damage response. J Cell Biochem 100:883–896PubMedCrossRefGoogle Scholar
  6. Hollstein M, Shomer B, Greenblatt M, Soussi T, Hovig E, Montesano R, Harris CC (1996) Somatic point mutations in the p53 gene of human tumors and cell lines: updated compilation. Nucleic Acids Res 24:141–146PubMedCrossRefGoogle Scholar
  7. Huelsenbeck JP, Ronquist F (2001) MRBAYES: Bayesian inference of phylogenetic trees. Bioinformatics 17:754–755PubMedCrossRefGoogle Scholar
  8. Jost CA, Marin MC, Kaelin WG Jr (1997) p73 is a human p53-related protein that can induce apoptosis. Nature 389:191–194PubMedCrossRefGoogle Scholar
  9. King N (2004) The unicellular ancestry of animal development. Dev Cell 7:313–325PubMedCrossRefGoogle Scholar
  10. Kelley ML, Winge P, Heaney JD, Stephens RE, Farell JH, Van Beneden RJ, Reinisch CL, Lesser MP, Walker CW (2001) Expression of homologues for p53 and p73 in the softshell clam (Mya arenaria), a naturally occurring model for human cancer. Oncogene 20:748–758PubMedCrossRefGoogle Scholar
  11. Levrero M, De Laurenzi V, Costanzo A, Sabatini S, Gong J, Wang JYJ, Melino G (2000) The p53/p63/p73 family of transcription factors: overlapping and distinct functions. J Cell Sci 113:1661–1670PubMedGoogle Scholar
  12. Locascio A, Vega S, de Frutos CA et al (2002) Biological potential of a functional human SNAIL retrogene. J Biol Chem 277:38803–38809PubMedCrossRefGoogle Scholar
  13. Manzanares M, Blanco MJ, Nieto MA (2004) Snail3 orthologues in vertebrates: divergent members of the Snail zinc-finger gene family. Dev Genes Evol 214:47053CrossRefGoogle Scholar
  14. Mendoza L, Orozco E, Rodriguez MA, Garcia-Rivera G, Sanchez T, Garcia E, Gariglio P (2003) Ehp53, an Entamoeba histolytica protein, ancestor of the mammalian tumour suppressor p53. Microbiology 149:885–893PubMedCrossRefGoogle Scholar
  15. Moll UM, Slade N (2004) p63 and p73: Roles in development and tumor formation. Mol Cancer Res 2:371–386PubMedGoogle Scholar
  16. Murray-Zmijewski F, Lane DP, Bourdon J-C (2006) p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress. Cell Death Diff 13:962–72CrossRefGoogle Scholar
  17. Muttray AF, Cox RL, St-Jean S, van Poppelen P, Reinisch CL, Baldwin SA (2005) Identification and phylogenetic comparison of p53 in two distinct mussel species (Mytilus). Comp Biochem Physiol C Toxicol Pharmacol 140:237–250PubMedCrossRefGoogle Scholar
  18. Ollmann M, Young YM, Di Como CJ, Karim F, Belvin M, Robertson S, Whittaker K, Demsky M, Fisher WW, Buchman A, Duyk G, Friedman L, Prives C, Kopczynski C (2000) Drosophila p53 is a structural and functional homolog of the tumor suppressor p53. Cell 101:91–101PubMedCrossRefGoogle Scholar
  19. Rennert J, Coffman JA, Mushegian AR et al (2003) The evolution of Runx genes I. A comparative study of sequences from phylogenetically diverse model organisms. BMC Evol Biol 3:4PubMedCrossRefGoogle Scholar
  20. Schumacher B, Hofmann K, Boulton S, Gartner A (2001) The C. elegans homolog of the p53 tumor suppressor is required for DNA damage-induced apoptosis. Curr Biol 11:1722–1727PubMedCrossRefGoogle Scholar
  21. Yang A, Kaghad M, Wang Y, Gillet E, Fleming MD, Dotsch V, Andrews NC, Caput D, McKeon F (1998) p63, a p53 homolog at 3q27–29, encodes multiple products with transactivating, death-inducing, and domain-negative activities. Mol Cell 2:305–316PubMedCrossRefGoogle Scholar
  22. Yang A, Kaghad M, Caput D, McKeon F (2002) On the shoulders of giants: p63, p73, and the rise of p53. Trends Genet 18:90–95PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of BiologyUniversity of New BrunswickFrederictonCanada

Personalised recommendations