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1. Shannon, C. E. Bell Syst. Tech. J. 27, 379–423, 623–656 (1948).2. Horodecki, M., Oppenheim, J. & Winter, A. Nature 436,

673–676 (2005).3. Slepian, D. & Wolf, J. K. IEEE Trans. Inform. Theory 19,

461–480 (1971).4. Bell, J. S. Physics 1, 195–200 (1964); reprinted in

Bell, J. S. Speakable and Unspeakable in Quantum

Mechanics (Cambridge Univ. Press, 1987).5. Aczel, A. D. Entanglement: The Greatest Mystery in Physics

(Wiley, London, 2002). 6. Bennett, C. H. et al. Phys. Rev. Lett. 70, 1895–1899 (1993).7. Cerf, N. J. & Adami, C. Phys. Rev. Lett. 79, 5194–5197 (1997).8. Yard, J., Devetak, I. & Hayden, P. preprint at

http://arxiv.org/abs/quant-ph/0501045 (2005).

models a community as a finite collection ofindividuals that have identical probabilities ofreproduction, death and dispersal. This yieldspredictions for community properties in termsof parameters that govern the stochasticchanges that the community undergoes — forexample the immigration or dispersal rate, thespeciation rate, and the size of the community.Despite its simplicity, neutral theory’s predic-tions have proven robust. Claims that it hasbeen falsified4 have been followed by persua-sive counter-arguments5.

Graves and Rahbek mount a new line ofattack on neutral theory by testing it at thescale of an entire continent. Armed with animpressive bird-distribution database amassedfrom the collections of over 30 museums in 20countries, as well as a global land-cover mapcreated from satellite data, they quantify thecorrelation between the distribution of habitat

(or land-cover type ) and the distribution ofbirds across South America at the resolution of1� latitude by 1� longitude grid cells.

Put simply, Graves and Rahbek find thatbirds in more widespread habitats tend to be more wide-ranging. In particular, birds present in the lowland regions of the continentto the east of the Andes, where elevationchanges slowly and habitats are widespread,are on average an order of magnitude morewide-ranging than those on the western side of the Andes, where topographic relief is at a maximum and habitat changes quickly inspace (Fig. 1a). Furthermore, as one looks out-wards from various locations on the continent,the change in bird-community composition is asymmetric and mimics the underlyingchanges in habitat (Fig. 1b).

Graves and Rahbek conclude that there is astrong causal influence of birds’ habitat require-ments on their spatial distribution across SouthAmerica. They argue that this influence con-tradicts neutral theory, which ignores speciesdifferences in habitat requirements.

It is worth pointing out that the first ofGraves and Rahbek’s results, a correlationbetween habitat extent and species’ spatialextents, could arise from a source other thanhabitat influence, a source that is instead con-sistent with neutral theory. The Andes act as aphysical barrier to the dispersal of both birdsand the flora that cover the landscape. Thisbarrier, combined with the very different landareas available to dispersing species to the westand east of it, could alone explain the observedcorrelation.

But there are no dispersal barriers to explainthe relationship between community compo-sition and the distribution of riverside habitatevident in Fig. 1b. And further study of the

ECOLOGY

Neutral theory tested by birds Annette Ostling

A continental-scale analysis of habitat and bird distribution in SouthAmerica provides the latest challenge for neutral theory — a controversialidea in ecology about what determines the make-up of communities.

How do different species end up livingtogether in communities? Do they coexist onlywhen each finds a different niche, or simplywhen they happen to disperse to the same habitable region? Debate over these questionsintensified not long ago with the introductionof ‘neutral theory’1, a stochastic theory of community properties whose predictions haveproven stubbornly robust, despite its disregardof the niches that many ecologists hold dear.Writing in Proceedings of the National Acad-emy of Sciences, however, Graves and Rahbek2

point out continental-scale patterns in the birdcommunities of South America that neutraltheory may not be able to explain.

The dominant view in ecology is that specieslive together in communities only when theydiffer from one another. Species competing for the same nutrient or food source cannotcoexist because one species will always bemore efficient than the others and will quicklydrive the rest to extinction3. Species that co-exist must differ from one another in theresource they use most efficiently or in theenvironmental conditions to which they are best adapted — that is, they must have different niches. This view is often called‘niche-assembly’.

The contrary viewpoint is that communitiesare primarily shaped by historical accidentsthat influence where species disperse (a beetlefloating to a distant island on flotsam, forexample, or the uplift of a mountain range thatblocks the flight of seeds between nearbyforests). This view has deeper roots in evolu-tionary biology, where history is at centre stage,than in ecology, which concentrates on short-term interactions between species. The ideabehind it is that, rather than being quickly out-competed, species that are less efficient at usinga resource evolve to be as efficient as their com-petitors. The main criterion for coexistence is dispersal to the same habitable region. Thisview is sometimes called ‘dispersal-assembly’.

The neutral theory tested by Graves andRahbek2 is the modern synthesis of dispersal-assembly into a mathematical framework. It

Figure 1 | Summary of Graves and Rahbek’s results2. a, Bird species in the lowland regions of SouthAmerica, where habitat types are more widespread, are more wide-ranging than those on the westernedge of the continent, where the Andes create quick changes in elevation and habitat type. Coloursindicate median range-size in units of 1� latitude � 1� longitude cells. b, The composition of birdcommunities changes asymmetrically as one looks outwards from a location in the Amazon basin (here 1–2� S, 69–70� W), mimicking the underlying distribution of riverside habitat. Colours indicatethe number of species in common with the focal location whose coordinates are listed. Neutral theorymay be consistent with a but Graves and Rahbek are correct that it cannot predict the ecologicalimportance of habitat evident in b. The theory may still be relevant at smaller scales, however, andspecies differences in habitat requirements can evolve under dispersal-assembly on a heterogeneouslandscape. (Figures reproduced from ref. 2.)

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bird and land-cover databases would surelyyield quantitative evidence of the influence ofhabitat. Practically all ecologists agree thatspecies have habitat requirements that limitwhere they can live — tropical trees cannotsurvive on the Arctic tundra. Graves and Rahbek are correct that neutral theory cannotpredict the resulting influence of habitat oncommunity composition because it ignoresspecies differences entirely.

But does the importance of habitat disagreewith the letter or the intent of neutral theory?In other words, does it contradict the overallprinciple of dispersal-assembly?

Not necessarily. The idea of dispersal-assembly is not that differences betweenspecies do not exist — they are the inevitableresult of disparate evolutionary histories.Rather, the idea is that species similarities, nottheir differences, lead them to find the sameregion habitable and to coexist. Neutral theoryapplies only in that realm of intermingling,where species are similar.

Habitat influence on species’ distributions at any scale does indicate a role for niche-assembly, which has implications for ecologi-cal dynamics. The species that differ in thehabitat they do best in cannot out-competeeach other. Their differences allow them tocoexist stably in the landscape.

However, unless habitat and species changein lock-step, habitat effects do not rule out asimultaneous role for dispersal-assembly. AsGraves and Rahbek acknowledge, their obser-vations limit only the spatial scale and groupsof species within which neutral theory’s unsta-ble ecological dynamics may apply. Further-more, differences between species in habitatrequirements can arise from sources that are consistent with dispersal-assembly in aheterogeneous landscape over evolutionarytimescales, such as from local selection forcapabilities on a par with those of competitors.Selection for the avoidance of competition (orniche-assembly) may not be the evolutionaryorigin of these differences.

More empirical work is needed to distin-guish between niche-assembly and dispersal-assembly on both ecological and evolutionarytimescales. We also need to understand theimplications of this distinction, and morerefined ones, for judging the robustness andresilience of communities in the face ofanthropogenic change. ■

Annette Ostling is in the Department of Ecologyand Evolutionary Biology, Guyot Hall, Princeton University, Princeton, New Jersey 08544-1003, USA.e-mail: aostling@princeton.edu

1. Hubbell, S. P. The Unified Neutral Theory of Biodiversity andBiogeography (Princeton Univ. Press, 2001).

2. Graves, G. R. & Rahbek, C. Proc. Natl Acad. Sci. USA 102,7871–7876 (2005).

3. Hardin, G. Science 131, 1292–1297 (1960).4. Clark, J. S. & MacLachlan, J. S. Nature 423, 625–638

(2003).5. Volkov, I., Banavar, J. R., Maritan, A. & Hubbell, S. P. Nature

427, 696 (2004).

expression in nevi, and experimental deple-tion of p16INK4a failed to increase BRAF-induced senescence in melanocyte cultures.Mutated BRAF in melanocytes also failed toinduce the ARF and p53 tumour suppressors,two proteins integral to the activation of senes-cence in many systems. These results exposeserious gaps in our understanding of the genesand pathways that function to constrain thetransformation of nevi into lethal melanomas.

Exploring the evolution of prostate cancer,Chen et al. (page 725)2 discovered senescencein early-stage prostate abnormalities inhumans and in mice engineered to sustainprostate-specific deletion of the PTENtumour-suppressor gene. However, in contrastto the situation in melanocytes, prostate OIS isdependent on p53, and co-deletion of PTENand p53 cancelled senescence, promoting full-blown prostate cancer. Parallel studies usingmouse models to dissect the role of the Rasoncogene in the lung and pancreas3 and inlymphoid cells4 reinforced similar principles.So, although previous work has establishedthat the role of p53 as a tumour suppressordepends on its ability to mediate apoptosis,these papers emphasize that p53 can alsomediate senescence in primary tumours.

Collado et al. (page 642)3 address a crucialneed for better in vivo markers of OIS. So far,the gold standard has been the detection of anenzymatic activity associated with senescence(that of SA-�-gal)7. Although SA-�-gal hasbeen used successfully to analyse human andmouse samples, this marker is not molecularlywell-defined and demonstrates backgroundactivity in certain organs. Collado et al.employed an ingenious microarray screen toidentify a small set of genes, the expression ofwhich correlates strongly with senescenceinduced by the ERK protein. (ERK mediatesthe effects of certain cancer-causing muta-tions.) The correlations with gene expressionare not seen when ERK is induced in theabsence of senescence. These markers of OISinclude protein-encoding genes and at leastthree RNA-encoding genes that are relevant tomouse tumour models of different tissues.These markers might predict OIS in pre-cancerous abnormalities in humans.

Braig et al. (page 660)4 provide a penetratingbiochemical view of senescence. Their experi-ments were guided by the observation ofunusual foci of tightly packed DNA in senes-cent cells8. These foci possessed features of aform of silenced DNA called heterochromatin,

CANCER

Crime and punishmentNorman E. Sharpless and Ronald A. DePinho

Cellular senescence stops the growth of cells. This process, first glimpsed in cell culture, is now confirmed by in vivo evidence as a vital mechanismthat constrains the malignant progression of many tumours.

Societies have traditionally taken threeapproaches to handling recidivist criminals:exile, execution and lifetime imprisonment. Itseems that human cells use similar strategiesto prevent rogue cells harbouring dangerousmutations from turning into fully fledged can-cers. Epithelial tissue, such as that lining theairways and intestines, continuously renewsand sloughs off, thereby sentencing some pre-cancerous cells to extra-corporeal exile. Thereis also a cellular version of the death penalty —apoptosis, a well-established anticancer mech-anism. And in this issue, four groups1–4 reportstriking in vivo evidence that the body cansubject potential cancer cells to the equivalentof a life-sentence: cellular senescence.

Senescence is a specific form of stablegrowth arrest provoked by diverse stresses,including the enforced expression of cancer-promoting genes in cultured cells. This ‘onco-gene-induced senescence’ (OIS)5 is linked to known cancer pathways in cultured cells,notably the ARF–p53 and p16INK4a–RB path-ways (Fig. 1). But whether OIS is an authen-tic anticancer process in vivo, or simply anartefact of enforced oncogene expression incells experiencing culture shock6, has beencontroversial.

This issue is settled by the new papers1–4,which show that OIS occurs in vivo in severaldiverse precancerous tissues from both humanand mouse. In addition, the work identi-fies much-needed markers of senescence, and further delineates the molecular under-pinnings of this key tumour-suppressingprocess. A compelling feature of these studiesis the consistency of OIS in response to a vari-ety of cancer-causing mutations in differenthuman tumour types and mouse-model systems. At the same time, the reports revealthat the molecular circuitry of OIS may bewired differently among tumour types.

Michaloglou et al. (page 720)1 worked withcultures of human melanocytes (pigmentedskin cells) and nevi (skin moles, the benignprecursors of malignant melanoma). Theyfound that nevi harbouring mutations of theBRAF protein (mutations that are frequentlyfound in melanomas) have robust expressionof senescence markers and do not seem to proliferate. In melanoma cells, however, senescence is extinguished and proliferationaccelerated.

Curiously, the tumour suppressor p16INK4a

— a known activator of senescence that isdeleted in melanoma cells — showed spotty

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