theory and multiscale modelling in this andother areas. ■

G. S. Cargill III is in the Department of MaterialsScience and Engineering, Lehigh University,Bethlehem, Pennsylvania 18015, USA.e-mail: gsc3@lehigh.edu1. Röntgen, W. C. Nature 53, 274–276 (1896).

2. Compton, A. H. & Allison, S. K. X-rays in Theory and

Experiment 2nd edn (Van Nostrand, New York, 1935).3. Friedrich, W., Knipping, P. & von Laue, M. Sber. Bayer. Akad.

Wiss. 303 (1912).4. Larson, B. C., Yang, W., Ice, G. E., Budal, J. D. & Tischler, J. Z.

Nature 415, 887–890 (2002).5. Tamura, N. et al. Mater. Res. Soc. Proc. 563, 175–180 (1999).6. Chang, C.-H., MacDowell, A. A., Padmore, H. A. & Patel, J. R.

Mater. Res. Soc. Proc. 524, 55–58 (1998).7. Spolenak, R. et al. Mater. Res. Soc. Proc. 621, D10.3.1–D10.3.7

(2000).

sequence to reveal new features of S. pombebiology, and to uncover further evidence ofhow different the fission and budding yeastsare. For example, S. pombe has hundreds ofgenes that are apparently absent in S. cere-visiae, and vice versa. The genetic differencesare not as great in some areas as S. pomberesearchers may have hoped; for example,there are only three disease-linked humangenes that have counterparts in S. pombe butnot in S. cerevisiae. But overall the differencesare quite significant, and show why S. cere-visiae may not always be the preferred modeleukaryote.

For instance, Wood et al. find that, com-pared with S. cerevisiae, S. pombe has signifi-cantly more ‘intron’ sequences (roughly4,700 compared with 275), which interruptthe coding regions of genes, and very fewtransposable — mobile — genetic elements.S. pombe also has more proteins that appearto be involved in transporting sugars or othermolecules; larger centromeres (chromo-some regions needed for the accurate parti-tioning of chromosomes after cell division);and an apparent lack of recent whole-genome duplication. These differences couldmake S. pombe a better model than S. cere-visiae for understanding some eukaryoticprocesses.

It does not particularly surprise me thatbudding and fission yeast differ so much atthe genomic level, as they are not very closelyrelated12, and many genetic and physical differences had been known before thegenomes were sequenced (see, for example,ref. 13). But the fact that many further differ-ences have been uncovered by genomic comparisons4 suggests that it could provevaluable to sequence the genomes of otherbiologically diverse yeast species, and, morebroadly, other fungi.

Wood et al. also attempt to identify genesthat might be specific to eukaryotes (and soprobably evolved on the branch of the evo-lutionary tree that separates these speciesfrom prokaryotes; Fig. 1). The authors use avery conservative approach, identifyingonly those genes that are highly conserved in eukaryotes and have no apparent matchesin any prokaryote, so they may have missedmany eukaryotic-specific genes. Neverthe-less, many of those identified are predictedto function in processes specific to, or highlydeveloped in, eukaryotes, such as the cellcycle, RNA ‘splicing’, construction of thecytoskeleton, protein degradation and sig-nal transduction. So these genes may be fundamental to understanding the originand evolution of eukaryotes. In a separateanalysis, Wood et al. identified protein‘domains’ — structurally defined portionsof proteins — that are more abundant ineukaryotes than in prokaryotes; these mayalso be important in understanding eukary-otic biology.

The S. pombe genome is the second of a

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NATURE | VOL 415 | 21 FEBRUARY 2002 | www.nature.com 845

Having a famous relative can be a mixedblessing. This is certainly the case forthe yeast Schizosaccharomyces pombe,

commonly referred to as ‘fission yeast’ bothbecause it divides by binary fission and todistinguish it from its distantly relatedcousin, Saccharomyces cerevisiae or ‘buddingyeast’. Saccharomyces cerevisiae is consideredby many to be the single-celled model forresearch into eukaryotes1 (those organisms,including humans, whose cells have adefined nucleus) and is also of major indus-trial importance. So, although those study-ing S. pombe have benefited from discoveriesabout S. cerevisiae, the fission yeast is oftenviewed as ‘the other yeast’, taking a back seatin research and funding.

Well, get ready everyone, because a fightfor glory is brewing in the yeast family. First, a few months ago, Paul Nurse wasannounced as co-winner of the 2001 NobelPrize in Physiology or Medicine, being

recognized largely for his work on the cellcycle in S. pombe2,3. Now, on page 871 of thisissue, Nurse and colleagues4 report on thesequencing and analysis of the complete S. pombe genome, officially bringing theother yeast into the post-genomics era.

Schizosaccharomyces pombe is the sixthfree-living eukaryotic species whose genomehas been reported as completely sequenced5–10.(Some, such as the human genome, havebeen announced as ‘completed’ even thoughthey are not; the S. pombe sequence is actually nearer to completion than many of the others.) The analyses presented in thenew paper, the sequence itself and the manybits of extra information available on web-sites devoted to S. pombe (see, for example,ref. 11) together represent a landmarkachievement. The analyses should also satisfy those who have asked: “Why anotheryeast genome?”.

Wood et al.4 use the S. pombe genome

Genome sequencing

Brouhaha over the other yeastJonathan A. Eisen

The sequencing of the fission-yeast genome allows researchers to compareit with that of its cousin, budding yeast, and to identify genes that maydistinguish eukaryotes (such as yeast) from prokaryotes (such as bacteria).

Figure 1 The tree of life, with the branches labelledaccording to Wood et al.’s analysis4 of genes that might

be specific to eukaryotes versus prokaryotes, and tomulticellular versus single-celled organisms. Bacteria and archaea are prokaryotes (they do not havenuclei). The eukaryotic part of the tree is based on ref. 18. Only representative lineages are shown.

Branches duringwhich eukaryoticgenes may haveevolved

Branches withoutcomplete genomesavailable

Branches leadingup to completegenomes analysed

Complete genomenot analysed here

Plants/algae

Giardia

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Diplomonads

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Bacteria ArchaeaEukaryotes

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© 2002 Macmillan Magazines Ltd

free-living, single-celled eukaryote to becompletely sequenced (the first being that of S. cerevisiae). Wood et al. take advantage ofthis to try to identify genomic properties thatare related to multicellularity. They usedanother conservative approach to comparethe genomes of the two yeast species with theavailable genome sequences of multicellulareukaryotes (a plant and three animals), andfound only three genes that were specific toall the multicellular species.

This may seem surprising, but it proba-bly should not. First, the comparison didnot take into account that multicellularity probably evolved separately in plants andanimals14 (Fig. 1), so different multicellu-larity-related genes may have evolved inthese two evolutionary lineages. Second, thetime interval during which these genescould have evolved is much shorter than for

the eukaryotic versus prokaryotic compari-son — in other words, there has been lesstime to ‘invent’ new genes. Perhaps moreusefully here, the authors found that, evenafter correcting for differences in genomesize, some protein domains are more com-mon in the multicellular than in the uni-cellular organisms, probably reflecting theexpansion of certain protein families. Thisimplies that such expansions may haveoccurred in parallel during the evolution of multicellular animals and plants, but thesame genes were rarely if ever invented byboth groups.

So what next? Clearly, a better compari-son of eukaryotes and prokaryotes requirescomplete genome sequences from a morediverse sampling, not just those eukaryotesfrom the ‘top’ of the tree (Fig. 1). Lumpedtogether as ‘protists’, these other eukaryotes

show remarkable diversity and include manyparasitic species, such as the malaria-causingPlasmodium; species such as Giardia thatlack the cellular powerhouses, mitochon-dria; and organisms with several nuclei andunusual genome-rearrangement processes,such as Tetrahymena. It will also be interest-ing to use the S. pombe and other fungalgenomes to do a more thorough comparisonwith genomes from the Microsporidia, suchas the parasitic Encephalitozoon15. Theseorganisms were once classified with the protists but are now thought to be related to fungi16.

In all these comparisons, it will be import-ant to go beyond simply identifying the similarities and differences between species,and to analyse the origin of the differences,for example the gain, loss and possible trans-fer of genes over time17. But today we should

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NATURE | VOL 415 | 21 FEBRUARY 2002 | www.nature.com 847

Marine archaeology

Acid attackIf you were planning to visitthe impressive restoration of the Vasa, now is a goodtime. The Vasa was a 61-metre,1,210-tonnewarship, which sank inStockholm harbour on itsmaiden voyage in 1628, butwas raised in 1961 andrestored for display in amuseum in Stockholm (see

pictures). A multidisciplinarygroup of researchers,however, has discovered that the ship’s timbers are in danger of disintegrating.As Magnus Sandström andcolleagues report in this issue (Nature 415, 893–897;2002), and describe in anexhibition that opens thisweek in the Vasa Museum,sulphuric acid is beingproduced within the beams of the ship. The acid attacksthe wood both chemically, byacid hydrolysis of cellulose,and physically, as thesulphate minerals expandduring crystallization.

So where is the sulphuricacid coming from? Alerted by sulphate crystals formingon the surface of the Vasa’stimbers, Sandström et al.went on to find largequantities of elementalsulphur inside the wood. They believe that hydrogensulphide — a commonproduct of bacterialdecomposition in anoxicwaters — permeated theship’s timbers and wasgradually transformed toelemental sulphur during the333 years that the ship lay at the bottom of Stockholmharbour. This created areservoir of sulphur, which, iffully oxidized, could produce

as much as five tonnes ofsulphuric acid.

A complicating factorcomes from the legacy of theship’s 9,000 original iron boltsthat have largely rusted away.Iron (III) ions are effectively acatalyst here, graduallyoxidizing elemental sulphur to sulphuric acid. Thereduced iron is then itself re-oxidized by oxygen fromthe air, ready to go throughthe cycle once more.

Museum curators arewell aware of the threat ofoxidation to waterloggedwooden artefacts aftersalvage. As well as stabilizingthe fragile lattice ofremaining wood by replacingthe water with non-volatilepreservatives, conservationmethods routinely involvelimiting further biological and chemical oxidation withsterilizing solutions, andcarefully controlling humidityand temperature. But thenewly observed sulphurthreat calls for differentmeasures. Neutralizing fivetonnes of sulphuric acid isnot really feasible, and themost promising solution liesin tackling the iron catalyst.One proposal of Sandström et al. is to identify an agentthat will form a complex withthe iron solutes, making them

inert, and possibly evenextractable by rinsing theship with alkali.

What about other wrecks?Fortunately, the Vasa seems to be an extreme case. Thedecision in the sixteenthcentury to close off two inletsinto Stockholm harbour, tohinder attack from theRussians, along with centuriesof sewage disposal in theharbour, helped to create an especially stagnant andsulphurous resting place.Moreover, the threat ofsulphur acidification in wrecksthat were completely buried in sediments, such as theMary Rose, now on display in Portsmouth, UK, should besmaller. Indeed, Sandström et al. found that sulphuraccumulation was greatest in

the exposed timbers of theVasa. But in ships that werenot buried — the Batavia ofthe Dutch East India Company,for instance, which waswrecked off Western Australiain 1629 — initial analysesconfirm that the sulphurproblem is more common, ifnot as severe as in the Vasa.

These new investigationssupport recent moves to letsunken ships lie, andpreserve and study themwhere they sank (Nature 415,460; 2002) — virtualtechnology would still allowthe public to view the wrecksand their sites. After all, why not capitalize on thepreserving features of marinesediments, rather than letthem express their acidic sidelater on? Jim Gillon

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From the standpoint of diversity in formand sheer number, the arthropods arethe most successful animals on Earth.

They embrace four remarkable groups: trilo-bites (sadly extinct), insects, crustaceans(shrimp, lobsters, crabs and so on), and chelicerates (horseshoe crabs, spiders and

scorpions). The success of the arthropodsstems, in part, from their modular archi-tecture. They are composed of a series ofrepeating body segments that can be modi-fied in seemingly limitless ways. Some segments carry wings, whereas others haveantennae, legs, feeding organs or specializedmating devices.

Another item can be added to the list ofthings that are special about the arthropods:we know more about the evolutionaryprocesses responsible for their diversifica-tion than for any other group of animals.These insights have been made possible bydetailed study of the genetic mechanismsunderlying the development of that mostthoroughly characterized of animals — aninsect, the fruitfly Drosophila melanogaster.After nearly a century of genetic analysis,many of the genes responsible for segmen-tation and limb development have beenidentified. Foremost among these is a class of regulatory genes, the Hox genes, whichencode DNA-binding proteins and controlearly development. During the past ten yearsthis information has been used in the bur-geoning field of ‘evo–devo’, which lies at thecusp of evolutionary biology and embryolo-gy, to determine how limbs have diversifiedamong different arthropods.

Children are taught that insects have sixlegs, two on each of the three thoracic (mid-dle) segments, and this applies to every oneof the more than a million species of insect.By contrast, other arthropods, such as crus-taceans, have a variable number of swim-ming limbs. Some crustaceans have limbs on every segment in both the thorax andabdomen. Papers on pages 910 and 914 ofthis issue, by Galant and Carroll1, and byRonshaugen et al.2, provide new insights into

how insects have lost abdominal limbs, andso contain only six legs.

The two groups1,2 provide evidence thatsuppression of abdominal limbs in insectsdepends on functional changes in a proteincalled Ultrabithorax (Ubx), which is encodedby a Hox gene. Ubx represses the expressionof another gene, Distalless (Dll ), which isrequired for limb formation, in the anteriorabdomen of the Drosophila embryo. How-ever, in crustaceans, such as the brine shrimpArtemia, all of the developing limbs havehigh levels of Ubx.

The other comparison to be made here is with velvet worms. These are members ofthe Onychophora — close relatives of thearthropods — which have limbs on all seg-ments. In velvet worms, Ubx is expressed in at least a subset of these limbs. So Ubxexpression is compatible with limb develop-ment in crustaceans and onychophorans,but is incompatible with limb developmentin Drosophila (and other insects).

The new work involved misexpression ofthe Drosophila Ubx protein in the presump-tive thorax of transgenic fruitfly embryos.Limb development was suppressed becauseof repression of Dll. By contrast, the mis-expression of onychophoran and crustaceanUbx proteins did not interfere with Dllexpression and the formation of thoraciclimbs. These results raised the possibilitythat the Drosophila Ubx protein is function-ally distinct from Ubx in onychophoransand crustaceans. One study suggests thatDrosophila Ubx has acquired an alanine-rich peptide that mediates the repression ofgene transcription; this peptide is lacking in

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848 NATURE | VOL 415 | 21 FEBRUARY 2002 | www.nature.com

Evolutionary biology

How insects lose their limbsMike Levine

Evolution has produced marvellous variety in the arthropods, and in their various appendages. The evolutionary processes are themselvesproving highly diverse.

Figure 1 Evolution through changes in Hoxprotein function. An interpretation of the newresults1,2 runs like this. Onychophorans, such as velvet worms, are close relatives of thearthropods, and have limbs on every segment.Here Ubx protein may function as an activator,but when onychophorans and arthropodsdiverged it acquired one or more repressiondomains, which suppressed limb development.In insects these domains mediate constitutiverepression of target genes, such as Antp and Dll. During the subsequent crustacean–insectdivergence, Ubx in crustaceans acquired aregulatory peptide containing potential CKIIphosphorylation sites, making Ubx act as aconditional repressor. In the brineshrimpArtemia, for instance, Ubx represses Antpwithout influencing the expression of Dll. An alternative view is that the onychophoranprotein contains both a repression domain and a regulatory peptide, the peptide being lostin insects but retained in crustaceans.

Figure 2 Evolution through changes in Hox gene expression. In crustaceans known asbranchiopods (top), the head contains feedingappendages, whereas thoracic segment T1,nearest the head, contains swimmingappendages that are like those further back onthe thorax (segments T2–T5). In these animals,expression of one Hox gene (Scr) is restricted to head segments, and Ubx is expressed in allthoracic segments. In other crustaceans, such asisopods (bottom), the first thoracic appendageshave been modified into feeding structurescalled maxillipeds. This change correlates with altered patterns of Hox gene expression:Ubx is replaced by Scr expression in the firstthoracic segment.

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do a little dance for the other yeast, and hopethat in the future, when someone says ‘yeast’,scientists will give equal thought to thespecies that was first isolated from a tradi-tional African beer known as Pombe. ■

Jonathan A. Eisen is at The Institute for GenomicResearch, 9712 Medical Center Drive, Rockville,Maryland 20850, USA.e-mail: jeisen@tigr.org1. Botstein, D., Chervitz, S. A. & Cherry, J. M. Science 277,

1259–1260 (1997).

2. Nasmyth, K. Cell 107, 689–701 (2001).

3. Nurse, P., Thuriaux, P. & Nasmyth, K. Mol. Gen. Genet. 146,

167–178 (1976).

4. Wood, V. et al. Nature 415, 871–880 (2002).

5. International Human Genome Sequencing Consortium Nature

409, 860–921 (2001).

6. Venter, J. C. et al. Science 291, 1304–1351 (2001).

7. The C. elegans Sequencing Consortium Science 282, 2012–2018

(1998).

8. Adams, M. D. et al. Science 287, 2185–2195 (2000).

9. Goffeau, A. et al. Science 274, 546–567 (1996).

10.The Arabidopsis Genome Initiative Nature 408, 796–815

(2000).

11.http://www.sanger.ac.uk/Projects/S_pombe

12.Sipiczki, M. Genome Biol. 1, 1011.1–1011.4 (2000).

13.Bowman, K. K. et al. Nucleic Acids Res. 22, 3026–3032 (1994).

14.Kaiser, D. Annu. Rev. Genet. 35, 103–123 (2001).

15.Katinka, M. D. et al. Nature 414, 450–453 (2001).

16.Hirt, R. P. et al. Proc. Natl Acad. Sci. USA 96, 580–585 (1999).

17.Eisen, J. A. & Hanawalt, P. C. Mutat. Res. 435, 171–213 (1999).

18.Baldauf, S. L., Roger, A. J., Wenk-Siefert, I. & Doolittle, W. F.

Science 290, 972–977 (2000).

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