Indigenous Arabs are descendants of the earliest split from ancient Eurasian populations.

An open question in the history of human migration is the identity of the earliest Eurasian populations that have left contemporary descendants. The Arabian Peninsula was the initial site of the out-of-Africa migrations that occurred between 125,000 and 60,000 yr ago, leading to the hypothesis that the first Eurasian populations were established on the Peninsula and that contemporary indigenous Arabs are direct descendants of these ancient peoples. To assess this hypothesis, we sequenced the entire genomes of 104 unrelated natives of the Arabian Peninsula at high coverage, including 56 of indigenous Arab ancestry. The indigenous Arab genomes defined a cluster distinct from other ancestral groups, and these genomes showed clear hallmarks of an ancient out-of-Africa bottleneck. Similar to other Middle Eastern populations, the indigenous Arabs had higher levels of Neanderthal admixture compared to Africans but had lower levels than Europeans and Asians. These levels of Neanderthal admixture are consistent with an early divergence of Arab ancestors after the out-of-Africa bottleneck but before the major Neanderthal admixture events in Europe and other regions of Eurasia. When compared to worldwide populations sampled in the 1000 Genomes Project, although the indigenous Arabs had a signal of admixture with Europeans, they clustered in a basal, outgroup position to all 1000 Genomes non-Africans when considering pairwise similarity across the entire genome. These results place indigenous Arabs as the most distant relatives of all other contemporary non-Africans and identify these people as direct descendants of the first Eurasian populations established by the out-of-Africa migrations.

Unlimited niche packing in a Lotka-Volterra competition game.

A central question in the study of ecology and evolution is: "Why are there so many species?" It has been shown that certain forms of the Lotka-Volterra (L-V) competition equations lead to an unlimited number of species. Furthermore, these authors note how any change in the nature of competition (the competition kernel) leads to a finite or small number of coexisting species. Here we build upon these works by further investigating the L-V model of unlimited niche packing as a reference model and evolutionary game for understanding the environmental factors restricting biodiversity. We also examine the combined eco-evolutionary dynamics leading up to the species diversity and traits of the ESS community in both unlimited and finite niche-packing versions of the model. As an L-V game with symmetric competition, we let the strategies of individuals determine the strength of the competitive interaction (like competes most with like) and also the carrying capacity of the population. We use a mixture of analytic proofs (for one and two species systems) and numerical simulations. For the model of unlimited niche packing, we show that a finite number of species will evolve to specific convergent stable minima of the adaptive landscape (also known as species archetypes). Starting with a single species, faunal buildup can proceed either through species doubling as each diversity-specific set of minima are reached, or through the addition of species one-by-one by randomly assigning a speciation event to one of the species. Either way it is possible for an unlimited number or species to evolve and coexist. We examine two simple and biologically likely ways for breaking the unlimited niche-packing: (1) some minimum level of competition among species, and (2) constrain the fundamental niche of the trait space to a finite interval. When examined under both ecological and evolutionary dynamics, both modifications result in convergent stable ESSs with a finite number of species. When the number of species is held below the number of species in an ESS coalition, we see a diverse array of convergent stable niche archetypes that consist of some species at maxima and some at minima of the adaptive landscape. Our results support those of others and suggest that instead of focusing on why there are so many species we might just as usefully ask, why are there so few species?

Pulmonary Abnormalities in Young, Light-Use Waterpipe (Hookah) Smokers.

RATIONALE: Waterpipes, also called hookahs, are currently used by millions of people worldwide. Despite the increasing use of waterpipe smoking, there is limited data on the health effects of waterpipe smoking and there are no federal regulations regarding its use. OBJECTIVES: To assess the effects of waterpipe smoking on the human lung using clinical and biological parameters in young, light-use waterpipe smokers. METHODS: We assessed young, light-use, waterpipe-only smokers in comparison with lifelong nonsmokers using clinical parameters of cough and sputum scores, lung function, and chest high-resolution computed tomography as well as biological parameters of lung epithelial lining fluid metabolome, small airway epithelial (SAE) cell differential and transcriptome, alveolar macrophage transcriptome, and plasma apoptotic endothelial cell microparticles. MEASUREMENTS AND MAIN RESULTS: Compared with nonsmokers, waterpipe smokers had more cough and sputum as well as a lower lung diffusing capacity, abnormal epithelial lining fluid metabolome profile, increased proportions of SAE secretory and intermediate cells, reduced proportions of SAE ciliated and basal cells, markedly abnormal SAE and alveolar macrophage transcriptomes, and elevated levels of apoptotic endothelial cell microparticles. CONCLUSIONS: Young, light-use, waterpipe-only smokers have a variety of abnormalities in multiple lung-related biological and clinical parameters, suggesting that even limited waterpipe use has broad consequences on human lung biology and health. We suggest that large epidemiological studies should be initiated to investigate the harmful effects of waterpipe smoking.

Risk of COPD with obstruction in active smokers with normal spirometry and reduced diffusion capacity.

Smokers are assessed for chronic obstructive pulmonary disease (COPD) using spirometry, with COPD defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as airflow limitation that is not fully reversible with bronchodilators. There is a subset of smokers with normal spirometry (by GOLD criteria), who have a low diffusing capacity of the lung for carbon monoxide (DLCO), a parameter linked to emphysema and small airway disease. The natural history of these "normal spirometry/low DLCO" smokers is unknown.From a cohort of 1570 smokers in the New York City metropolitian area, all of whom had normal spirometry, two groups were randomly selected for lung function follow-up: smokers with normal spirometry/normal DLCO (n=59) and smokers with normal spirometry/low DLCO (n=46). All had normal history, physical examination, complete blood count, urinalysis, HIV status, α1-antitrypsin level, chest radiography, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio and total lung capacity. Throughout the study, all continued to be active smokers.In the normal spirometry/normal DLCO group assessed over 45±20 months, 3% developed GOLD-defined COPD. In contrast, in the normal spirometry/low DLCO group, followed over 41±31 months, 22% developed GOLD-defined COPD.Despite appearing "normal" according to GOLD, smokers with normal spirometry but low DLCO are at significant risk of developing COPD with obstruction to airflow.

LOGICOIL--multi-state prediction of coiled-coil oligomeric state.

MOTIVATION: The coiled coil is a ubiquitous α-helical protein-structure domain that directs and facilitates protein-protein interactions in a wide variety of biological processes. At the protein-sequence level, the coiled coil is readily recognized via a conspicuous heptad repeat of hydrophobic and polar residues. However, structurally coiled coils are more complicated, existing in a wide range of oligomer states and topologies. As a consequence, predicting these various states from sequence remains an unmet challenge. RESULTS: This work introduces LOGICOIL, the first algorithm to address the problem of predicting multiple coiled-coil oligomeric states from protein-sequence information alone. By covering >90% of the known coiled-coil structures, LOGICOIL is a net improvement compared with other existing methods, which achieve a predictive coverage of ∼31% of this population. This leap in predictive power offers better opportunities for genome-scale analysis, and analyses of coiled-coil containing protein assemblies. AVAILABILITY: LOGICOIL is available via a web-interface at http://coiledcoils.chm.bris.ac.uk/LOGICOIL. Source code, training sets and supporting information can be downloaded from the same site.

Designed coiled coils promote folding of a recombinant bacterial collagen.

Collagen triple helices fold slowly and inefficiently, often requiring adjacent globular domains to assist this process. In the Streptococcus pyogenes collagen-like protein Scl2, a V domain predicted to be largely α-helical, occurs N-terminal to the collagen triple helix (CL). Here, we replace this natural trimerization domain with a de novo designed, hyperstable, parallel, three-stranded, α-helical coiled coil (CC), either at the N terminus (CC-CL) or the C terminus (CL-CC) of the collagen domain. CD spectra of the constructs are consistent with additivity of independently and fully folded CC and CL domains, and the proteins retain their distinctive thermal stabilities, CL at ∼37 °C and CC at >90 °C. Heating the hybrid proteins to 50 °C unfolds CL, leaving CC intact, and upon cooling, the rate of CL refolding is somewhat faster for CL-CC than for CC-CL. A construct with coiled coils on both ends, CC-CL-CC, retains the ∼37 °C thermal stability for CL but shows less triple helix at low temperature and less denaturation at 50 °C. Most strikingly however, in CC-CL-CC, the CL refolds slower than in either CC-CL or CL-CC by almost two orders of magnitude. We propose that a single CC promotes folding of the CL domain via nucleation and in-register growth from one end, whereas initiation and growth from both ends in CC-CL-CC results in mismatched registers that frustrate folding. Bioinformatics analysis of natural collagens lends support to this because, where present, there is generally only one coiled-coil domain close to the triple helix, and it is nearly always N-terminal to the collagen repeat.

SCORER 2.0: an algorithm for distinguishing parallel dimeric and trimeric coiled-coil sequences.

MOTIVATION: The coiled coil is a ubiquitous α-helical protein structure domain that directs and facilitates protein-protein interactions in a wide variety of biological processes. At the protein-sequence level, coiled coils are quite straightforward and readily recognized via the conspicuous heptad repeats of hydrophobic and polar residues. However, structurally they are more complicated, existing in a range of oligomer states and topologies. Here, we address the issue of predicting coiled-coil oligomeric state from protein sequence. RESULTS: The predominant coiled-coil oligomer states in Nature are parallel dimers and trimers. Here, we improve and retrain the first-published algorithm, SCORER, that distinguishes these states, and test it against the current standard, MultiCoil. The SCORER algorithm has been revised in two key respects: first, the statistical basis for SCORER is improved markedly. Second, the training set for SCORER has been expanded and updated to include only structurally validated coiled coils. The result is a much-improved oligomer state predictor that outperforms MultiCoil, particularly in assigning oligomer state to short coiled coils, and those that are diverse from the training set. AVAILABILITY: SCORER 2.0 is available via a web interface at http://coiledcoils.chm.bris.ac.uk/Scorer. Source code, training sets and Supporting Information can be downloaded from the same site.

Evolutionary game theory as a framework for studying biological invasions.

Although biological invasions pose serious threats to biodiversity, they also provide the opportunity to better understand interactions between the ecological and evolutionary processes structuring populations and communities. However, ecoevolutionary frameworks for studying species invasions are lacking. We propose using game theory and the concept of an evolutionarily stable strategy (ESS) as a conceptual framework for integrating the ecological and evolutionary dynamics of invasions. We suggest that the pathways by which a recipient community may have no ESS provide mechanistic hypotheses for how such communities may be vulnerable to invasion and how invaders can exploit these vulnerabilities. We distinguish among these pathways by formalizing the evolutionary contexts of the invader relative to the recipient community. We model both the ecological and the adaptive dynamics of the interacting species. We show how the ESS concept provides new mechanistic hypotheses for when invasions result in long- or short-term increases in biodiversity, species replacement, and subsequent evolutionary changes.

Evolution of cooperation with shared costs and benefits.

The quest to determine how cooperation evolves can be based on evolutionary game theory, in spite of the fact that evolutionarily stable strategies (ESS) for most non-zero-sum games are not cooperative. We analyse the evolution of cooperation for a family of evolutionary games involving shared costs and benefits with a continuum of strategies from non-cooperation to total cooperation. This cost-benefit game allows the cooperator to share in the benefit of a cooperative act, and the recipient to be burdened with a share of the cooperator's cost. The cost-benefit game encompasses the Prisoner's Dilemma, Snowdrift game and Partial Altruism. The models produce ESS solutions of total cooperation, partial cooperation, non-cooperation and coexistence between cooperation and non-cooperation. Cooperation emerges from an interplay between the nonlinearities in the cost and benefit functions. If benefits increase at a decelerating rate and costs increase at an accelerating rate with the degree of cooperation, then the ESS has an intermediate level of cooperation. The game also exhibits non-ESS points such as unstable minima, convergent-stable minima and unstable maxima. The emergence of cooperative behaviour in this game represents enlightened self-interest, whereas non-cooperative solutions illustrate the Tragedy of the Commons. Games having either a stable maximum or a stable minimum have the property that small changes in the incentive structure (model parameter values) or culture (starting frequencies of strategies) result in correspondingly small changes in the degree of cooperation. Conversely, with unstable maxima or unstable minima, small changes in the incentive structure or culture can result in a switch from non-cooperation to total cooperation (and vice versa). These solutions identify when human or animal societies have the potential for cooperation and whether cooperation is robust or fragile.

An evolutionary model of carcinogenesis.

A quantitative model of carcinogenesis based on methods from population biology and game theory demonstrates normal cells in vivo occupy a ridge-shaped maximum in a well-defined tissue fitness landscape, a novel configuration that allows cooperative coexistence of multiple cellular populations. This state, although necessary for development of functioning multicellular organisms, is subject to invasion by fitter, mutant phenotypes permitting somatic evolution of cancer. The model demonstrates carcinogenesis is an emergent phenomenon requiring a sequence of evolutionary steps as cellular proliferation follows successful adaptation to varying environmental constraints. In the initial development of preneoplastic lesions, cellular proliferation is controlled exclusively by interactions with other cells, the extracellular matrix, and soluble or insoluble growth factors so that gain of function mutations in oncogenes, loss of function mutations in tumor suppressor genes, and disruption of normal senescence pathways will permit clonal expansion. This provides explicit selection mechanisms for the mutations depicted in the classical Fearon-Vogelstein model of colorectal carcinogenesis. The model demonstrates neoplastic cellular proliferation can also be promoted by alterations in the somatic landscape that reduce inhibitory signals produced by the normal cells and extracellular matrix. This is consistent with experimental evidence for a strong microenvironmental influence in tumorigenesis independent of genomic changes in the neoplastic populations. However, we find that these changes alone produce only self-limited neoplastic growth because cellular crowding alters system dynamics so that proliferation is dependent on substrate availability. Consequent cellular competition for critical nutrients results in Darwinian selection pressures favoring phenotypes that increase substrate delivery (e.g., angiogenesis) or uptake (e.g., amplify membrane transporters). These previously unknown substrate dynamics in the later stages of carcinogenesis provide a mechanism for evolution of cellular properties typically found in invasive cancers including the angiogenic and glycolytic phenotypes.

Application of quantitative models from population biology and evolutionary game theory to tumor therapeutic strategies.

Quantitative models from population biology and evolutionary game theory frame the tumor-host interface as a dynamical microenvironment of competing tumor and normal populations. Through this approach, critical parameters that control the outcome of this competition are identified and the conditions necessary for formation of an invasive cancer are defined. Perturbations in these key parameters that destabilize the cancer solution of the state equations and produce tumor regression can be predicted. The mathematical models demonstrate significant theoretical limitations in therapies based solely on cytotoxic drugs. Because these approaches do not alter critical parameters controlling system dynamics, the tumor population growth term will remain positive as long as any individual cells are present so that the tumor will invariably recur unless all proliferative cells are killed. The models demonstrate that such total effectiveness is rendered unlikely by the genotypic heterogeneity of tumor populations (and, therefore, the variability of their response to such drugs) and the ability of tumor cells to adapt to these proliferation constraints by evolving resistant phenotypes. The mathematical models support therapeutic strategies that simultaneously alter several of the key parameters in the state equations. Furthermore, the models demonstrate that administration of cytotoxic therapies will, by reducing the tumor population density, create system dynamics more conducive to perturbations by biological modifiers.

Divergent and convergent evolution in metastases suggest treatment strategies based on specific metastatic sites.

BACKGROUND AND OBJECTIVE: Systemic therapy for metastatic cancer is currently determined exclusively by the site of tumor origin. Yet, there is increasing evidence that the molecular characteristics of metastases significantly differ from the primary tumor. We define the evolutionary dynamics of metastases that govern this molecular divergence and examine their potential contribution to variations in response to targeted therapies. METHODOLOGY: Darwinian interactions of transformed cells with the tissue microenvironments at primary and metastatic sites are analyzed using evolutionary game theory. Computational models simulate responses to targeted therapies in different organs within the same patient. RESULTS: Tumor cells, although maximally fit at their primary site, typically have lower fitness on the adaptive landscapes offered by the metastatic sites due to organ-specific variations in mesenchymal properties and signaling pathways. Clinically evident metastases usually exhibit time-dependent divergence from the phenotypic mean of the primary population as the tumor cells evolve and adapt to their new circumstances. In contrast, tumors from different primary sites evolving on identical metastatic adaptive landscapes exhibit phenotypic convergence. Thus, metastases in the liver from different primary tumors and even in different hosts will evolve toward similar adaptive phenotypes. The combination of evolutionary divergence from the primary cancer phenotype and convergence towards similar adaptive strategies in the same tissue cause significant variations in treatment responses particularly for highly targeted therapies. CONCLUSION AND IMPLICATIONS: The results suggest that optimal therapies for disseminated cancer must take into account the site(s) of metastatic growth as well as the primary organ.

Smoking dysregulates the human airway basal cell transcriptome at COPD risk locus 19q13.2.

Genome-wide association studies (GWAS) and candidate gene studies have identified a number of risk loci associated with the smoking-related disease COPD, a disorder that originates in the airway epithelium. Since airway basal cell (BC) stem/progenitor cells exhibit the earliest abnormalities associated with smoking (hyperplasia, squamous metaplasia), we hypothesized that smoker BC have a dysregulated transcriptome, enriched, in part, at known GWAS/candidate gene loci. Massive parallel RNA sequencing was used to compare the transcriptome of BC purified from the airway epithelium of healthy nonsmokers (n = 10) and healthy smokers (n = 7). The chromosomal location of the differentially expressed genes was compared to loci identified by GWAS to confer risk for COPD. Smoker BC have 676 genes differentially expressed compared to nonsmoker BC, dominated by smoking up-regulation. Strikingly, 166 (25%) of these genes are located on chromosome 19, with 13 localized to 19q13.2 (p<10⁻4 compared to chance), including 4 genes (NFKBIB, LTBP4, EGLN2 and TGFB1) associated with risk for COPD. These observations provide the first direct connection between known genetic risks for smoking-related lung disease and airway BC, the population of lung cells that undergo the earliest changes associated with smoking.

Prediction and analysis of higher-order coiled-coils: insights from proteins of the extracellular matrix, tenascins and thrombospondins.

α-Helical coiled-coil domains (CCDs) direct protein oligomerisation in many biological processes and are of great interest as tools in protein engineering. Although CCDs are recognizable from protein sequences, prediction of oligomer state remains challenging especially for trimeric states and above. Here we evaluate LOGICOIL, a new multi-state predictor for CCDs, with regard to families of extracellular matrix proteins. Tenascins, which are known to assemble as trimers, were the first test case. LOGICOIL out-performed other algorithms in predicting trimerisation of these proteins and sequence analyses identified features associated with many other trimerising CCDs. The thrombospondins are a larger and more ancient family that includes sub-groups that assemble as trimers or pentamers. LOGICOIL predicted the pentamerising CCDs accurately. However, prediction of TSP trimerisation was relatively poor, although accuracy was improved by analyzing only the central regions of the CCDs. Sequence clustering and phylogenetic analyses grouped the TSP CCDs into three clades comprising trimers and pentamers from vertebrates, and TSPs from invertebrates. Sequence analyses revealed distinctive, conserved features that distinguish trimerising and pentamerising CCDs. Together, these analyses provide insight into the specification of higher-order CCDs that should direct improved CCD predictions and future experimental investigations of sequence-to-structure functional relationships.

High correlation of the response of upper and lower lobe small airway epithelium to smoking.

The distribution of lung disease induced by inhaled cigarette smoke is complex, depending on many factors. With the knowledge that the small airway epithelium (SAE) is the earliest site of smoking-induced lung disease, and that the SAE gene expression is likely sensitive to inhaled cigarette smoke, we compared upper vs. lower lobe gene expression in the SAE within the same cigarette smokers to determine if the gene expression patterns were similar or different. Active smokers (n = 11) with early evidence of smoking-induced lung disease (normal spirometry but low diffusing capacity) underwent bronchoscopy and brushing of the upper and lower lobe SAE in order to compare upper vs lower lobe genome-wide and smoking-responsive gene expression by microarray. Cluster and principal component analysis demonstrated that, for each individual, the expression of the known SAE smoking-responsive genes were highly correlated in upper and lower lobe pairs, although, as expected, there were differences in the smoking-induced changes in gene expression from individual to individual. These observations support the concept that the heterogeneity observed among smokers in the anatomic distribution of smoking-induced disease are not secondary to the topographic differences in the effects of cigarette smoke on the airway epithelium.

A basis set of de novo coiled-coil peptide oligomers for rational protein design and synthetic biology.

Protein engineering, chemical biology, and synthetic biology would benefit from toolkits of peptide and protein components that could be exchanged reliably between systems while maintaining their structural and functional integrity. Ideally, such components should be highly defined and predictable in all respects of sequence, structure, stability, interactions, and function. To establish one such toolkit, here we present a basis set of de novo designed α-helical coiled-coil peptides that adopt defined and well-characterized parallel dimeric, trimeric, and tetrameric states. The designs are based on sequence-to-structure relationships both from the literature and analysis of a database of known coiled-coil X-ray crystal structures. These give foreground sequences to specify the targeted oligomer state. A key feature of the design process is that sequence positions outside of these sites are considered non-essential for structural specificity; as such, they are referred to as the background, are kept non-descript, and are available for mutation as required later. Synthetic peptides were characterized in solution by circular-dichroism spectroscopy and analytical ultracentrifugation, and their structures were determined by X-ray crystallography. Intriguingly, a hitherto widely used empirical rule-of-thumb for coiled-coil dimer specification does not hold in the designed system. However, the desired oligomeric state is achieved by database-informed redesign of that particular foreground and confirmed experimentally. We envisage that the basis set will be of use in directing and controlling protein assembly, with potential applications in chemical and synthetic biology. To help with such endeavors, we introduce Pcomp, an on-line registry of peptide components for protein-design and synthetic-biology applications.

The evolution and structure prediction of coiled coils across all genomes.

Coiled coils are α-helical interactions found in many natural proteins. Various sequence-based coiled-coil predictors are available, but key issues remain: oligomeric state and protein-protein interface prediction and extension to all genomes. We present SpiriCoil (http://supfam.org/SUPERFAMILY/spiricoil), which is based on a novel approach to the coiled-coil prediction problem for coiled coils that fall into known superfamilies: hundreds of hidden Markov models representing coiled-coil-containing domain families. Using whole domains gives the advantage that sequences flanking the coiled coils help. SpiriCoil performs at least as well as existing methods at detecting coiled coils and significantly advances the state of the art for oligomer state prediction. SpiriCoil has been run on over 16 million sequences, including all completely sequenced genomes (more than 1200), and a resulting Web interface supplies data downloads, alignments, scores, oligomeric state classifications, three-dimensional homology models and visualisation. This has allowed, for the first time, a genomewide analysis of coiled-coil evolution. We found that coiled coils have arisen independently de novo well over a hundred times, and these are observed in 16 different oligomeric states. Coiled coils in almost all oligomeric states were present in the last universal common ancestor of life. The vast majority of occasions that individual coiled coils have arisen de novo were before the last universal common ancestor of life; we do, however, observe scattered instances throughout subsequent evolutionary history, mostly in the formation of the eukaryote superkingdom. Coiled coils do not change their oligomeric state over evolution and did not evolve from the rearrangement of existing helices in proteins; coiled coils were forged in unison with the fold of the whole protein.

COEVOLUTION AS AN EVOLUTIONARY GAME.

Coevolution is modeled as a continuous game where the fitness-maximizing strategy of an individual is assumed to be a function of the strategy of other individuals who are also under selection to maximize fitness. An evolutionary stable strategy (ESS) is sought such that no rare alternative strategies can invade the community. The approach can be used to model coevolution because the ESS may be composed of a coalition of more than one strategy. This work, by modeling frequency-dependent selection, extends the approach of Roughgarden (1976) which only considered density-dependent selection. In particular, we show that the coevolutionary model of Rummel and Roughgarden (1985) does contain frequency-dependent selection, and thus, their application of Roughgarden's criterion for evolutionary stability to a model for which it is not applicable leads to the erroneous conclusion that the ecological and evolutionary processes are in conflict. The utility of the game theoretic approach is illustrated by two examples. The first considers an ESS composed of a single strategy, the second an ESS composed of a coalition of two strategies. Evolution occurs on a frequency-dependent adaptive landscape. For this reason, the approach is appropriate for modeling competitive speciation (Rosenzweig, 1978). Also, the game theoretic approach is designed to combine the interplay between the background environment (including the biotic components) and the evolutionary potential of the populations or organisms. The actual application of this theory will require knowledge of both.

ORGANIZATION OF PREDATOR-PREY COMMUNITIES AS AN EVOLUTIONARY GAME.

We consider a simple predator-prey model of coevolution. By allowing coevolution both within and between trophic levels the model breaks the traditional dichotomy between coevolution among competitors and coevolution between a prey and its predator. By allowing the diversity of prey and predator species to emerge as a property of the evolutionarily stable strategies (ESS), the model breaks another constraint of most approaches to coevolution that consider as fixed the number of coevolving species. The number of species comprising the ESS is influenced by a parameter that determines the predator's niche breadth. Depending upon the parameter's value the ESS may contain: 1) one prey and one predator species, 2) two prey and one predator, 3) two prey and two predators, 4) three prey and two predators, 5) three prey and three predators, etc. Evolutionarily, these different ESSs all emerge from the same model. Ecologically, however, these ESSs result in very different patterns of community organization. In some communities the predator species are ecologically keystone in that their removal results in extinctions among the prey species. In others, the removal of a predator species has no significant impact on the prey community. These varied ecological roles for the predator species contrasts sharply with the essential evolutionary role of the predators in promoting prey species diversity. The ghost of predation past in which a predator's insignificant ecological role obscures its essential evolutionary role may be a frequent property of communities of predator and prey.