What We Can Learn From a Lowly Sponge

Red spongeWhen you hear the word “sponge”, what comes to mind? Perhaps your favorite bath-time cleaning implement? It turns out that the humble sponge can do more than just scrub away dirt; it can provide researchers with a glimpse into the evolution of multicellular organisms. In a recent Nature paper (1), Mansi Srivastava et al. presented the genome sequence of Amphimedon queenslandica, a demosponge from the Great Barrier Reef. What makes this paper interesting isn’t the sequence itself, but rather what we can learn from it.

Sponges are generally recognized as the oldest surviving Metazoan (i.e., multicellular member of the Animal Kingdom). Although sponges lack some of the basic features of the higher Eumetazoans (i.e., “true” animals) such as a gut and nervous system, they share a number of key genes involved in the six hallmarks of multicellular organisms: 1) regulation of cell cycle and growth, 2) programmed cell death, 3) cell-cell and cell-matrix adhesion, 4) developmental signaling and gene regulation, 5) allorecognition and innate immunity and 6) specialization of cell types. Thus, analysis of the sponge genome may provide valuable insight into which genes were required for the evolution of multicelluar organisms and the origin of those genes.

Srivastava et al. determined that the A. queenslandica genome exhibits significant conservation of gene structure and genome organization compared to the genome of other animals and has ~30,000 predicted protein-coding loci, of which 18,693 (63%) have identifiable homologs in other organisms. Many of these genes belong to one of the 1,286 metazoan-specific gene families, which emerged during the ~150- to 200-million-year period before sponges diverged from other animals (i.e., the metazoan stem; see Figure 1 of the Nature paper). During this time period, nearly 75% of these animal-specific gene families arose through gene duplication and divergence, and 235 animal-specific protein domains and 769 combinations of animal-specific domains evolved. Examples include homeodomain proteins and basic helix-loop-helix domains (2,3). Likewise, there was a significant expansion of proteins that contain the immunoglobulin-like domain and are involved in cellular recognition, binding or adhesion. The authors identified 218 predicted immunoglobulin-like domain-containing proteins in Amphimedon but only 5 in Monosiga brevicollis, a closely-related but nonmetazoan organism.

Some of these newly evolved animal-specific genes combined with more ancient gene products to provide novel functionalities or regulatory mechanisms. A good example illustrates the evolution of the p53-mediated apoptotic response to DNA damage: The p53/p63/p73 tumor suppressor family is found in organisms more primitive than metazoans; however, the homeodomain-interacting protein kinase that activates p53 in the presence of DNA breaks is metazoan-specific, and the MDM2 ubiquitin ligase that regulates p53 is eumetazoan-specific.

In addition, the ligands, receptors and transcription factors involved in signaling pathways that determine cellular identity and direct morphogenesis are all metazoan-specific. However, many of the cytosolic signal transducers pre-date metazoans. This suggests that new pathways arose through the interaction of novel ligands and receptors with existing signaling mechanisms.

The Amphimedon genome also revealed interesting clues about how and when certain tissues may have evolved. The presence of post-synaptic and proneural regulatory protein orthologs in Amphimedon implies the existence of an ancestral protoneuron. However, some key synaptic proteins are missing. Thus, although the metazoan ancestor possessed a complex sensory system, a complex nervous system was not possible until evolutionary advancements were made by the eumetazoans. Also, sponges do not have a mesoderm, and appropriately, the Amphimedon genome seems to lack transcription factors involved in mesoderm development. However, despite the lack of a neuromuscular system, sponges do have several transcription factors associated with determination or differentiation of nerves and muscle cells.

Finally, one last point that I found interesting: The Amphimedon genome encodes caspases, which are key cysteine proteases involved in both the intrinsic and extrinsic apoptosis pathways. The intrinsic apoptosis pathway, which involves permeabilization of the outer mitochondrial membrane, is likely the original mechanism for inducing apoptosis because some of the necessary components have more ancient origins and predate metazoans.

Thus, the lowly sponge can teach us a great deal about our own evolution and the evolution of other animals. How much more can we gleen from its DNA? Perhaps a lot, and some of that information could have important implications. Researchers have known for some time that many genes associated with multicellularity are also implicated in cancer and autoimmune disorders, which are nothing more than aberrant regulation of cell growth and immunity, respectively. It makes me wonder: How much more can we learn from the humble sponge?


  1. Srivastava M. et al. (2010). The Amphimedon queenslandica genome and the evolution of animal complexity. Nature, 466, 720–7 PMID: 20686567
  2. Simionato, E. et al. (2007) Origin and diversification of the basic helix-loop-helix gene family in metazoans: Insights from comparative genomics. BMC Evol. Biol. 7, 33.
  3. Larroux, C. et al. (2008) Genesis and expansion of metazoan transcription factor gene classes. Mol. Biol. Evol. 25, 980–96.
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Terri Sundquist

Terri has worked as a Scientific Communications Specialist at Promega Corporation for more than 13 years, and prior to that, spent more than 5 years solving problems and answering questions as a Promega Technical Services Scientist. She graduated with B.S. degrees in Chemistry and Biology at the University of Wisconsin—River Falls, then earned her M.S. in Molecular Biology from the Mayo Graduate School in Rochester Minnesota.


  1. Hi Terri,

    Interesting post.

    I am curious, do you have a citation for following:
    A good example illustrates the evolution of the p53-mediated apoptotic response to DNA damage: The p53/p63/p73 tumor suppressor family is found in organisms more primitive than metazoans;


    1. Hi Emily,
      Srivastava’s paper about Amphimedon queenslandica contains the passage: “Although the core machinery of the animal cell cycle traces back to early eukaryotes, some critical metazoan regulatory mechanisms emerged more recently. For example, whereas the p53/p63/p73 tumour suppressor family is holozoan-specific [King, N. et al. (2008) Nature 451, 783–8.], the HIPK kinase that phosphorylates p53 in the presence of DNA breaks is metazoan-specific, and the MDM2 ubiquitin ligase that regulates p53 appears as a eumetazoan feature. Thus, the p53-mediated response to DNA damage may have emerged before the divergence of eumetazoans.” So, since holozoans are more primitive than metazoans, the King paper is one citation to support that statement.
      If you expand your view to the p53/p63/p73 tumor suppressor superfamily, there are more examples. Rachael Rutkowski, Kay Hofmann and Anton Gartner wrote a detailed review of p53 gene superfamily evolution entitled “Phylogeny and Function of the Invertebrate p53 Superfamily”; see http://cshperspectives.cshlp.org/content/2/7/a001131.full. In this paper, they provide examples of p53 superfamily members that are present in more primitive organisms. For example: “The most ancient of the p53 superfamily proteins can be found in Choanozoans, single celled organisms thought to have preceded animal evolution. Monosiga brevicollis (Mb) encodes two p53 superfamily members whereas Capsaspora owczarzaki contains one (Nedelcu and Tan 2007; King et al. 2008; Broad Institute, ongoing sequencing project).” If you are interested in the evolution of p53 and p53-like proteins, I highly recommend reading this article.

  2. Thanks, now I am confused. I’m not a molecular biologist, just a lowly toxicologist trying to make sense of this all for a chapter on the evolution of cancer I am writing up.

    So I’ve read several recent papers/reviews on p53 which suggest that P53 (as it is) appears in vertebrates, while there is a related p63/p73 hybrid in inverts reaching back to the starlet anemone. (This is from Belyi et al., if I interpreted correctly.) There is also some kind of p53 splice product (not sure what that means) in inverts like clams and possibly mussels – not sure how to interpret that.

    But then there are p53 superfamily members in choanozoans – so does that mean its not p63/p73 hybrid exactly and definitely no p53, but something related to the whole family?

  3. Hi Emily,
    Gene evolution and alternative splicing are complicated topics, so I highly recommend reading some basic Molecular Biology texts (You might start with a search of the “Books” listings on PubMed at: http://www.ncbi.nlm.nih.gov/sites/entrez) and the paper that I mentioned in my earlier comment, along with some of the related papers listed in the right margin. It would be impossible to cover these topics sufficiently here. I’ll try to provide some basics though.
    Many gene superfamilies start out with one founding member, and over time, that original gene mutates and often becomes duplicated to form other members. Those other family members also change and evolve over time. For that reason, the sequences of genes in a family are usually similar but not identical in different phylogenetic classes of organisms. In general, the more closely related the organism, the more closely related the gene sequence. A gene family is defined by some scientists as those genes that have >50% sequence identity, whereas a gene superfamily is more inclusive and contains genes that are obviously related based on shared DNA sequences but the overall sequence identity is <50%.
    From what little I have read, I have learned that most invertebrates appear to have p53-related and p63-related genes; these differ from vertebrate p53 and p63 sequences due to changes during evolution. There is debate about whether invertebrate p53 superfamily members are phylogenetically more related to vertebrate p53 or p63. Rutkowski's phylogenetic analysis supports a conclusion that the p63-like sequence is evolutionarily more ancient.
    When you ask "But then there are p53 superfamily members in choanozoans – so does that mean its not p63/p73 hybrid exactly and definitely no p53, but something related to the whole family?" I assume that the p63/p73 "hybrid" refers to the common genetic ancestor of the p63 and p73 genes (i.e., the gene before p63 and p73 diverged into two separate genes). This hybrid would be distinct from (but related to) p53, which seems to have split off evolutionarily after p63 and p73 diverged. Without doing a more in-depth literature search, I don't know the exact nature of the p53 superfamily members that exist in choanozoans and other primitive organisms (i.e., whether they are considered p63/p73 hybrids ). As per the definition of a superfamily, the p53 superfamily members present in choanozoans must be related to p53, although they appear to be more closely related evolutionarily to p63 and p73.
    I am sure that there are other readers out there who are more knowledgeable about the p53 gene superfamily than I. Does anyone else care to join in the discussion and shed some light?

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