Oh happy day, the Sea Urchin Genome Project has reached fruition with the publication of the full sequence in last week’s issue of Science. This news has been all over the web, I know, so I’m late in getting my two cents in, but hey, I had a busy weekend, and and I had to spend a fair amount of time actually reading the papers. They didn’t just publish one mega-paper, but they had a whole section on Strongylocentrotus purpuratus, with a genomics mega-paper and articles on ecology and paleogenomics and the immune system and the transcriptome, and even a big poster of highlights of sea urchin research (but strangely, very little on echinoderm development). It was a good soaking in echinodermiana.
I also browsed the web to see what was being reported about this landmark event. It was decidedly mixed. There were lots of decent summaries, but there were also two themes running through many of the headlines that I found annoying. First is exemplified by this: Decoded sea urchin genome shows surprising relationship to humans. That’s just wrong. One of the major rationales for sequencing the urchin genome was precisely because it is a non-chordate deuterostome—that is, it’s not a member of our phylum, but it is a member of a phylum that is one of the most closely related to ours. Perhaps “surprising” should be replaced with “expected”. Additionally, I don’t think the main interest here should be the animal’s similarity to us; what we have here is an example of a major lineage in metazoan evolution that stands on its own as a subject of great value.
Another trend that compounds the humancentric problem is the taint of biomedical speculation: Sea urchin genome could shed light on human disease, which you can also see in the print media. Here, the emphasis is on odd little factlets: they can live for over a century! They never get cancer! You, too, can someday hope to acquire the virtues of sessile or slow moving aquatic grazers and filter feeders! Again, these reports miss the real excitement of understanding a little more about a different organism.
So why should we care about the echinoderm genome? One reason is that we have well over a century of research on this organism, and it represents one of the key model systems in developmental biology. Every developmental biology instructor, when it comes time to explain the concept of regulation, probably starts with Driesch’s experiments, in which 4-cell echinoderm embryos were dissociated and subsequently developed into perfect, tiny, and complete larvae. Nowadays, they are still key players in understanding the molecular circuitry of developmental regulation.
Another reason is their position in metazoan phylogeny. Two major groups separated over half a billion years ago, the protostomes and deuterostomes. To understand the properties of the last common ancestor of the deuterostome line, we need to sample widely across the extant phyla in that clade, and limiting ourselves to just the vertebrates would give us a biased view. Would studying just mice, for instance, be sufficient to understand vertebrate diversity? Information about chordates, hemichordates, and echinoderms is necessary to get a clearer picture of the evolution of these groups, just as we need to know about both arthropods and molluscs to understand the protostomes, and we need all of them together to figure out the evolution of the Bilateria. And, of course, we need to widen our view to the fungi and plants and bacteria and protists to understand the evolution of life.
The echinoderms are a diverse and successful group, with a rich evolutionary history and many different extant forms. They’ve generally followed a very different ecological strategy than their cousins, the chordates, and so they represent an illustration of the degree of variation possible within the deuterostome plan. We want to learn how they achieve those differences.
And look at them! They’re beautiful! They have ancestral similarities to chordates (check out the gill slits on the stylophorans), but they also have their own unique innovations, like the stereom and other aspects of their skeletons, and pentameral symmetry. What are the molecular correlates of those cool echinoderm specializations? Having the genome in hand is a tool to figure out the mechanisms behind those echinoderm specialties.
That’s why I think these organisms are interesting ones, well worth the expense of a genome project, and much more. What have we learned so far? One important lesson I emphasize strongly is that having a genome sequence is only the very beginning: it is a collection of hard-earned raw data that is a tool for analysis and experiment and isn’t entirely an end in itself. With that in mind there are a few general results that I found fascinating, not entirely unexpected, and that complement our understanding of metazoan evolution.
The raw size of the genome is about 814 million bases (about a quarter the size of ours) and contains about 23,000 genes (about the same as ours, but because the count is the product of some automated procedures, expect that number to go down somewhat—still, it’s of the same order of complexity as ours). Keep in mind, too, that Strongylocentrotus purpuratus is a model organism, selected for properties that make it compatible with laboratory work, and probably has a stripped-down genome compared to other echinoderms. There’s nothing magically, amazingly sophisticated about the human genome—we are comparable in complexity to a purple algae-eater.
If you want to see into the machinery and puzzle out where the truly significant changes have been going on, what aspects of life had been most strongly affected by natural selection, you have to look into something we take for granted: the immune system. Echinoderms lack the adaptive immune system we have—that is, a set of genes that are rapidly modified somatically to generate a specific immune response—but have a greatly expanded, effective innate immune system. There is a separate paper on just the immune system of sea urchins; I think there are plans afoot to summarize that paper on the Panda’s Thumb.
Another significant difference is in the assembly of the skeleton. Vertebrates use calcium hydroxyapatite, while echinoderms use calcium carbonate (calcite), and there are suites of genes present in echinoderms and not us, and vice versa, all associated with these structures.
Sea urchins look to be deaf and blind with no discrete eyes or hearing organs, but they do have an unexpectedly rich repertoire of genes associated with sensory functions. These include a set of photoreceptor genes. They don’t have eyes, so they don’t have an image forming apparatus, but they do express opsins in their tube feet, which means they can at least have a general sensation of light levels and perhaps even wavelengths in their environment. The authors also report the presence of transcription factors involved in retinal development in vertebrates—what they’re doing in the retina-less echinoderm is unknown.
As you might guess, I’m most interested in the genes involved in development. Analysis of the RNA present in the mid- to late-gastrula stage showed transcripts of 12-13,000 genes…which would suggest that over half the genome is involved in the early events of development. It’s a provocative figure, but I have my doubts, given both the uncertainty of the actual total number of genes and the fact that assaying expression doesn’t necessarily mean that these genes are actually doing anything significant. I’ll believe a more robust developmental genetic analysis when it’s done.
Almost all of the known bilaterian transcription factors are represented in the urchin—no surprise there, and it just reinforces the idea of a general metazoan genetic toolkit. They report that 80% of the transcription factors are expressed in the gastrula, but again, I’ll refer you to the caveats in the previous point. That’s not at all impossible, though; we know that genes are pleiotropic and are reused over and over again at different stages of development.
One class of developmentally significant genes, the Wnt signalling factors, were singled out for study. The urchin has 11 of the 13 known Wnt subfamilies (vertebrates have 12 of 13), but with fewer representatives in each family. That means there is less redundancy in the signaling pathways, but the pathways are effectively all present, and the patterns of interactions are again probably roughly equivalent in complexity between the two phyla.
I was unkind to those websites that played up the human disease connection in this research, but to be fair, the authors also emphasize it, in what I thought was a very unconvincing way.
The refinement of the inventory of vertebrate-specific or protostome-specific genes likewise benefits from the sea urchin genome. Many more human genes have shared ancestry across the deuterostomes, and in fact, bilaterian genes are more broadly shared than had been inferred from comparison of the previously limited genome sequences. The new biological niche sampled by the sea urchin genome provides not only a clearer view of the deuterostome and bilaterian ancestor, but has also provided a number of surprises. The finding of sea urchin homologs for sensory proteins related to vision and hearing in humans may lead to interesting new concepts of perception, and the extraordinary organization of the sea urchin immune system is different from any animal yet studied. From a practical standpoint, the sea urchin may be a treasure trove. Because of the many pathways shared by sea urchin and human, the sea urchin genome includes a large number of human disease gene orthologs. Many of the genes described in the preceding sections fall into this category and cover a surprising diversity of systems such as nervous, endocrine, and blood systems, as well as muscle and skeleton, as exemplified by the Huntington and muscular dystrophy genes. Continued exploration of the sea urchin immune system is expected to uncover additional variations for protection against pathogens. The immense diversity of pathogen-binding motifs encoded in the sea urchin genome provides an invaluable resource for antimicrobial applications and the identification of new deuterostome immune functions with direct relevance to human health. These exciting possibilities show that much biodiversity is yet to be uncovered by sampling additional evolutionary branches of the tree of life.
OK. Orthologs to genes involved in human disease leaves me cold; in most cases, we don’t understand how damage to these genes is generating the disease in humans, so I’m unclear on how identifying an ortholog to a human muscular dystrophy gene is going to add much to medicine just yet, even though it can be very useful in basic biology. The argument that the urchin immune system is obviously effective, yet with very different molecular components, and that can lead to new antimicrobial agents…that I find more promising.
But I still have to say that I’m disappointed that the paper ends on such an anthropocentric note. Echinoderms are extremely nifty in their own right, and we shouldn’t have to justify the work by going on and on about their utility to one species of ape.
Bottjer DJ, Davidson EH, Peterson KJ, Cameron RA (2006) Paleogenomics of Echinoderms. Science 314(5801):956-960.
Samanta MP, Tongprasit W, Istrail S, Cameron RA, Tu Q, Davidson EH, Stolc V. Sodergren E, Weinstock GM, Davidson EH, Cameron RA, Gibbs RA, Angerer RC, Angerer LM, Arnone MI, Burgess DR, Burke RD, Coffman JA, Dean M, Elphick MR, Ettensohn CA, Foltz KR, Hamdoun A, Hynes RO, Klein WH, Marzluff W, McClay DR, Morris RL, Mushegian A, Rast JP, Smith LC, Thorndyke MC, Vacquier VD, Wessel GM, Wray G, Zhang L, Elsik CG, Ermolaeva O, Hlavina W, Hofmann G, Kitts P, Landrum MJ, Mackey AJ, Maglott D, Panopoulou G, Poustka AJ, Pruitt K, Sapojnikov V, Song X, Souvorov A, Solovyev V, Wei Z, Whittaker CA, Worley K, Durbin KJ, Shen Y, Fedrigo O, Garfield D, Haygood R, Primus A, Satija R, Severson T, Gonzalez-Garay ML, Jackson AR, Milosavljevic A, Tong M, Killian CE, Livingston BT, Wilt FH, Adams N, Belle R, Carbonneau S, Cheung R, Cormier P, Cosson B, Croce J, Fernandez-Guerra A, Geneviere AM, Goel M, Kelkar H, Morales J, Mulner-Lorillon O, Robertson AJ, Goldstone JV, Cole B, Epel D, Gold B, Hahn ME, Howard-Ashby M, Scally M, Stegeman JJ, Allgood EL, Cool J, Judkins KM, McCafferty SS, Musante AM, Obar RA, Rawson AP, Rossetti BJ, Gibbons IR, Hoffman MP, Leone A, Istrail S, Materna SC, Samanta MP, Stolc V, Tongprasit W, Tu Q, Bergeron KF, Brandhorst BP, Whittle J, Berney K, Bottjer DJ, Calestani C, Peterson K, Chow E, Yuan QA, Elhaik E, Graur D, Reese JT, Bosdet I, Heesun S, Marra MA, Schein J, Anderson MK, Brockton V, Buckley KM, Cohen AH, Fugmann SD, Hibino T, Loza-Coll M, Majeske AJ, Messier C, Nair SV, Pancer Z, Terwilliger DP, Agca C, Arboleda E, Chen N, Churcher AM, Hallbook F, Humphrey GW, Idris MM, Kiyama T, Liang S, Mellott D, Mu X, Murray G, Olinski RP, Raible F, Rowe M, Taylor JS, Tessmar-Raible K, Wang D, Wilson KH, Yaguchi S, Gaasterland T, Galindo BE, Gunaratne HJ, Juliano C, Kinukawa M, Moy GW, Neill AT, Nomura M, Raisch M, Reade A, Roux MM, Song JL, Su YH, Townley IK, Voronina E, Wong JL, Amore G, Branno M, Brown ER, Cavalieri V, Duboc V, Duloquin L, Flytzanis C, Gache C, Lapraz F, Lepage T, Locascio A, Martinez P, Matassi G, Matranga V, Range R, Rizzo F, Rottinger E, Beane W, Bradham C, Byrum C, Glenn T, Hussain S, Manning FG, Miranda E, Thomason R, Walton K, Wikramanayke A, Wu SY, Xu R, Brown CT, Chen L, Gray RF, Lee PY, Nam J, Oliveri P, Smith J, Muzny D, Bell S, Chacko J, Cree A, Curry S, Davis C, Dinh H, Dugan-Rocha S, Fowler J, Gill R, Hamilton C, Hernandez J, Hines S, Hume J, Jackson L, Jolivet A, Kovar C, Lee S, Lewis L, Miner G, Morgan M, Nazareth LV, Okwuonu G, Parker D, Pu LL, Thorn R, Wright R. (2006) The Genome of the Sea Urchin Strongylocentrotus purpuratus. Science 314(5801):941-952.