AUTHOR=Huntly Nancy , Freischel Audrey R. , Miller Anna K. , Lloyd Mark C. , Basanta David , Brown Joel S. TITLE=Coexistence of “Cream Skimmer” and “Crumb Picker” Phenotypes in Nature and in Cancer JOURNAL=Frontiers in Ecology and Evolution VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/ecology-and-evolution/articles/10.3389/fevo.2021.697618 DOI=10.3389/fevo.2021.697618 ISSN=2296-701X ABSTRACT=

Over 40 years ago, seminal papers by Armstrong and McGehee and by Levins showed that temporal fluctuations in resource availability could permit coexistence of two species on a single resource. Such coexistence results from non-linearities or non-additivities in the way resource supply translates into fitness. These reflect trade-offs where one species benefits more than the other during good periods and suffers more (or does less well) than the other during less good periods, be the periods stochastic, unstable population dynamics, or seasonal. Since, coexistence based on fluctuating conditions has been explored under the guises of “grazers” and “diggers,” variance partitioning, relative non-linearity, “opportunists” and “gleaners,” and as the storage effect. Here we focus on two phenotypes, “cream skimmers” and “crumb pickers,” the former having the advantage in richer times and the latter in less rich times. In nature, richer and poorer times, with regular or stochastic appearances, are the norm and occur on many time scales. Fluctuations among richer and poorer times also appear to be the norm in cancer ecosystems. Within tumors, nutrient availability, oxygen, and pH can fluctuate stochastically or periodically, with swings occurring over seconds to minutes to hours. Despite interest in tumor heterogeneity and how it promotes the coexistence of different cancer cell types, the effects of fluctuating resource availability have not been explored for cancer. Here, in the context of pulsed resources, we (1) develop models of foraging consumers who experience pulsed resources to examine four types of trade-offs that can promote coexistence of phenotypes that do relatively better in richer versus in poorer times, (2) establish that conditions in tumors are conducive for this mechanism, (3) propose and empirically explore biomarkers indicative of the two phenotypes (HIF-1, GLUT-1, CA IX, CA XII), and (4) and compare cream skimmer and crumb picker biology and ecology in nature and cancer to provide cross-disciplinary insights into this interesting, and, we argue, likely very common, mechanism of coexistence.