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MAPK activation cascade. Furthermore, theCdc2 and MAPK pathways activate eachother. Except for the synthesis of a few keyproteins such as Mos and cyclin, most of thesignalling and feedback events in this systemconsist of phosphorylation6.

Despite this wealth of molecular infor-mation about egg maturation, and theappreciation of positive feedback in the mol-ecular circuitry, until now no one couldexplain how eggs persist in the mature state— with high Cdc2 and MAPK activity —long after progesterone has been removed.Ferrell and Xiong previously carried out theoretical studies of the problem8, andfound that positive feedback such as thatseen in the Cdc2 and MAPK cascades couldcreate a biochemical ‘memory’. This pre-diction was certainly not intuitive, as thesefeedback events operate largely by phospho-rylation — known to be rapid and readilyreversible. Was it not more likely that a long-term response to a transient signal would bemaintained by an irreversible event, such asthe destruction of a key regulatory protein,maybe an inhibitor of Cdc2 or MAPK?

It appears not.Proof of Ferrell and Xiong’stheoretical prediction required careful exp-erimentation. In particular, the predictiondemands that inhibiting the positive feed-back will cause a mature egg to ‘de-mature’, atleast with respect to key biochemical events.The authors now have compelling evidenceto support this idea1. They find that three different treatments that block the positivefeedback between MAPK and Mos result intransient, rather than sustained, activation ofboth MAPK and Cdc2. So, positive feedbackis necessary to maintain the biochemicalmemory of a mature egg (Fig. 1). Xiong andFerrell also provide an additional, theoreticalexplanation for their data, with compu-tational simulations that show how an essentially reversible switch can be renderedirreversible depending on the strength of thepositive feedback in the system.

Beyond its particular contributionsregarding the maturation of eggs,the work ofXiong and Ferrell1 should have much broaderimpact owing to the approach they presentfor addressing questions of cellular function.As in work regarding the cellular switch thatcontrols entry into, and exit from, nucleardivision9,10, Xiong and Ferrell’s experimentswere driven by theoretical predictions aboutthe fundamental mechanisms that controlsuch switches.These predictions derive froma systems-level view, but require quantita-tive, reductionist-style experimentation totest their validity. The ability to think andwork on such a broad scale, from systemthrough to molecule, is the most impressiveaspect of Xiong and Ferrell’s work. Thenotion of pairing theoretical and computa-tional biology with experimental cell biologyshould catch on, and the positive feedbackinherent in this interdisciplinary brand of

Planetary science

Conveyed to the Kuiper beltRodney Gomes

The small icy bodies that make up the Kuiper belt are the most distantobjects known in the Solar System. A consistent picture is now emergingwhich suggests that these objects formed much closer to the Sun.

Since the first member of the Kuiperbelt was discovered1 in 1992, manyunexpected features of their orbits

and physical properties have been uncov-ered. One surprise was the very low totalmass observed in the belt — about one-tenthof the mass of the Earth, when it was predict-ed to be a hundred times larger than that. Toexplain the missing mass, it has been pro-posed that collisions between Kuiper-beltobjects over the lifetime of the Solar Systemhave gradually transformed most of theirmass into dust; bombarded by solar radia-tion,these dust grains are eventually expelledfrom the Solar System. But such theorieshave never been able to satisfactorily explainthe extent of the depletion of the original

Kuiper-belt mass. On page 419 of this issue,Levison and Morbidelli2 propose an alterna-tive. They show that some objects that nowexist in the Kuiper belt might have beenpushed there from original positions nearNeptune’s present orbit: the original Kuiper-belt region could, in fact, have been virtuallyempty, and only a small amount of mass wassubsequently deposited there.

According to current theory,the planets ofthe Solar System formed from a primordialdisk of gas and dust, as the dust accumulatedinto gradually larger objects. Of course, ingoing from dust to planets there must havebeen intermediate stages, such as a disk offledgling planets,or planetesimals,of roughlyasteroid size. In regions where the total mass

Figure 1 Expansion plan. The primordial, compact Solar System (left) was surrounded by a disk ofasteroid-size planetesimals, which extended roughly as far as Neptune’s present orbit. Thegravitational pull of this disk eventually induced a planetary migration, during which the orbits of allthe major planets (except Jupiter) expanded. As a consequence, most planetesimals experienced closeencounters with the planets and were ejected from the Solar System. A few remnants were pushed outinto stable orbits, forming the present-day Kuiper belt (right). Two distinct, yet complementary,mechanisms of gravitational interaction explain how these remnants became divided between high-inclination orbits3 and low-inclination orbits2, with respect to the plane of the Solar System.

Highinclination

Lowinclination

Neptune

Kuiper belt

Neptune

Disk

Neptune

Plane of theSolar System

Planetesimal disk

Primordial Solar System

Present Solar System

Expansion

Sun Sun

science is likely to drive many breakthroughsin our understanding of cellular controls. ■

Jill C. Sible is in the Biology Department, VirginiaPolytechnic Institute and State University, DerringHall, Blacksburg, Virginia 24061-0406, USA.e-mail: siblej@v.edu

1. Xiong, W. & Ferrell, J. E. Jr Nature 426, 460–465 (2003).

2. Masui, Y. & Markert, C. L. J. Exp. Zool. 177, 129–145

(1971).

3. Gautier, J., Norbury, C. H., Lohka, M., Nurse, P. & Maller, J. L.

Cell 54, 433–439 (1988).

4. Gautier, J. et al. Cell 60, 487–494 (1990).

5. Kosako, H., Gotoh, Y. & Nisheda, E. EMBO J. 13, 2131–2138

(1994).

6. Schmitt, A. & Nebreda, A. R. J. Cell Sci. 115, 2457–2459 (2002).

7. Abrieu, A., Doree, M. & Fisher, D. J. Cell Sci. 114, 257–267 (2001).

8. Ferrell, J. E. Jr & Xiong, W. Chaos 11, 227–236 (2001).

9. Pomerening, J. R., Sontag, E. D. & Ferrell, J. E. Jr Nature Cell

Biol. 5, 346–351 (2003).

10.Sha, W. et al. Proc. Natl Acad. Sci. USA 100, 975–980 (2003).

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NATURE | VOL 426 | 27 NOVEMBER 2003 | www.nature.com/nature 395

in the disk was not large enough for the accu-mulation process to produce planets, thisplanetesimal disk would have been preservedto the present day.This would certainly be thecase for the Kuiper belt: because of its lessdense mass distribution and large distancefrom the Sun,the accretion process in the beltwould have ended when object sizes were nobigger than Pluto.However, in contrast to thepresent estimate for the Kuiper-belt mass,this accretion theory would require there tobe around 10 Earth masses in the Kuiper-beltregion, to allow the formation of objects asbig as those presently seen in the belt.

The paucity of mass in the Kuiper belt isnot the only enigma. Lying at such great dis-tances from the rest of the Solar System, andexperiencing no great perturbations fromother large bodies, Kuiper-belt objects wereexpected to have orbits that were nearly circu-lar and located close to the average plane ofthe Solar System. In fact, the orbits are quiteeccentric, and are inclined out of the SolarSystem plane (Fig. 1). Planetary scientistshave wondered how these orbits could havebeen so dynamically excited. My own idea3 isthat these objects formed much closer to theSun and were then propelled outwards by a mechanism involving close gravitationalencounters with the outward-migrating, pri-mordial Neptune. Other work4 shows that, ifthere had originally been a large mass beyondNeptune’s present position,this planet wouldhave moved much further out than it is today(effectively, into the Kuiper-belt region).

Thus, the puzzle seemed to be nearlysolved.On the one hand,the original planetes-imal disk would be truncated near Neptune’spresent position (Fig. 1), and was massiveenough to form the large bodies nowobserved in the Kuiper belt; on the otherhand, some objects would have been trans-ported to the belt from this dense inner planetesimal disk by a mechanism thatinduced high-inclination orbits throughclose encounters with Neptune3. However,there was one piece that didn’t fit. In additionto the Kuiper-belt objects in high-inclinationorbits, there is a roughly equal number ofobjects at low inclination. These could nothave been pushed out by the same mechanism.

Levison and Morbidelli2 propose a solu-tion. Their premise is based on anotherenigma — the fact that the Kuiper belt isconsidered to have an outer edge at about7�109 km from the Sun (equivalent to 48 AU, or astronomical units). This distanceis significant: at this point, the orbital periods of Kuiper-belt objects are twice that of Neptune, a feature known as the ‘1:2 mean motion resonance’. As Neptunemigrated outwards through the primordialSolar System, it pushed out some of theobjects in this resonance trap5,6. This mech-anism would naturally create orbit eccen-tricities, causing the resonant objects toapproach close to Neptune and the other

Comparative genomics

Two worms are better than oneMark Blaxter

The genome of the microscopic worm Caenorhabditis briggsae hasbeen sequenced, and shows some remarkable differences from thegenome of the better known — and physically similar — C. elegans.

In the early 1960s, when biologist SydneyBrenner was searching for a new modelorganism with which to study animal

development and neurobiology, he screeneda wide range of invertebrate species andchose the nematode Caenorhabditis elegansbecause it is easy to culture and transparentat all stages of its life cycle1. This small wormis now famous, not least for being the firstanimal to have its whole genome sequenced2.A close relative of C. elegans also passed byBrenner’s microscope, and narrowly missedthis accolade. This creature, C. briggsae, isphysically very similar to C. elegans (it takesan expert to distinguish them), and the twohave near-identical biology, even down tothe minutiae of developmental processes.Surprisingly, however, their genomes are notso similar, as the sequencing of the C. brig-gsae genome to around 98% completion,reported in Public Library of Science Biology,now reveals3. Comparing the two speciesoffers a new view of the patterns and process-es that have shaped genomes, and raisesmany questions for the future.

From the first draft of the C. elegansgenome2, it was predicted that this micro-scopic worm has more than 19,000 protein-coding genes and 1,000 RNA-encodinggenes. With the completion of the sequenceto the last base pair (all 100,258,171 of

them4) in late 2002, these numbers havegrown respectively to around 21,000 and3,000.There is still vigorous debate as to howmany of these genes are actually functional5,but what is clear is that the complexity of theC. elegans gene set contrasts markedly withthe organism’s morphological simplicity.For comparison, the more physically com-plicated fruitfly Drosophila melanogaster hasonly around 15,000 protein-coding genes6,and humans have some 40,000 (refs 7,8).

The C. briggsae sequence reported byStein et al.3, with its 19,500 protein-codinggenes, provides comparative confirmation ofmost of the C. elegans gene set and, surpris-ingly, suggests that there may be another1,300 C. elegans genes to add to the list. Steinet al. also propose more than 4,800 changes tocurrent C. elegans gene predictions, such asthe existence of new exons (the coding partsof genes, as opposed to their intervening,non-coding regions). These refinements willbe crucial in exploiting this nematode as amodel system. There are also some fascinat-ing differences between the two species (why,for instance, does C. elegans have more than700 chemoreceptor genes when C. briggsaegets by on just 430?), and many genes uniqueto each (about 800 per species).

Two other pairs of related genomes havebeen sequenced: humans7,8 and mice9 last

major planets, such that they would eventu-ally be ejected from the Solar System after afinal gravitational encounter with Jupiter.

Levison and Morbidelli argue, however,that the influence of other, so-called secularresonances, inside the 1:2 resonance, wouldhave kept the eccentricities and inclinationsof some resonant objects low.A secular reso-nance is also based on commensurability ofperiods — not of the periods of the objects’motion around the Sun, but instead of themotion of the orbits themselves around the Sun. Such resonances are powerful,and can induce large variations in orbitaleccentricities and inclinations, either raisingor lowering them. According to Levison and Morbidelli’s simulations, a small frac-tion of the resonance-trapped objects,once released through the rather jumpymigration of Neptune, would eventually beleft in fairly low-inclination orbits in theKuiper belt, owing to the influence of secular resonances. A few other objects remaining in the 1:2 resonance would set up the

outer edge of the Solar System as it is today.Of course, this new set of ideas raises

further questions. The main one is, howcould the primordial Solar System be formedin a truncated disk? The few observationsmade of other planetary systems as they areforming indicate that they have radiallyexpanded disks. Is the Solar System then arare case? Regardless of the answer, whatconditions could cause this truncation of adeveloping planetary system? This, I believe,will be a major topic in planetary science for years to come. ■

Rodney Gomes is at the Observatório do Valongo,Universidade Federal do Rio de Janeiro,and at the Observatório Nacional,Ladeira do Pedro Antonio 43, Rio de Janeiro 20080-090, Brazil.e-mail: rodney@ov.ufrj.br1. Luu, J. & Jewitt, D. Nature 362, 730–732 (1993).

2. Levison, H. F. & Morbidelli, A. Nature 426, 419–421 (2003).

3. Gomes, R. S. Icarus 161, 404–418 (2003).

4. Gomes, R. S., Morbidelli, A. & Levison, H. F. Icarus (in the press).

5. Malhotra, R. Nature 365, 819–821 (1993).

6. Malhotra, R. Astron. J. 110, 420–429 (1995).