The Role of "Thrifty Genes" in the Evolution of American Indian Health Issues

February 2009

by James T. Watson, assistant curator of bioarchaeology, Arizona State Museum and Daniel C. Benyshek, associate professor of anthropology, University of Nevada Las Vegas

The modern "Metabolic Syndrome" (cardiovascular disease, hypertension, obesity and type-2 diabetes) has disproportionately affected indigenous communities globally compared to their industrialized counterparts. This is especially salient in the Sonoran Desert where American Indians suffer from the highest rates of type-2 diabetes in the world. Genetic research since 1960 proposes that indigenous groups are genetically predisposed to these conditions because they possess a "thrifty genotype," genes that have been selected in response to periods of feast or famine in the past.

In an article published in the American Journal of Physical Anthropology (AJPA 131:120-126 (2006)) we chose to test the basic assumptions of the thrifty genotype model by analyzing ethnographic nutritional data from 94 foraging and preindustrial agricultural groups from around the world and tested the hypothesis that foragers are more likely to suffer from 'feast or famine' cycles than agriculturalists. We hypothesized that significant differences between foragers and agriculturalists with respect to one or more nutritional variables (quantity of available food, frequency of food  shortages, and extent of food shortages) would provide supportive evidence for the central tenet of the thrifty genotype hypothesis, i.e. that foragers are less food-secure than agriculturalists.

Our results revealed no significant differences between foragers and agriculturalists with respect to any of the three variables. While these findings are tentative, given the nature of the data used in cross-cultural ethnographic research, they are at odds with the thrifty-genotype proposition that past foraging populations suffer disproportionately from severe and frequent ''feast or famine'' cycles of nutrition, thereby providing a selective advantage for thrifty genotypes. The data presented here add to a growing body of research that calls into question assumptions about forager food insecurity (recently and in the prehistoric past), and the nutritional environment that might have selected for a thrifty genotype in past foraging populations.

Our findings suggest that food insecurity varies considerably within food-economy types, and that generalizations about food security based on food economy alone may be unwarranted. Future research would benefit from an evidence-based, population-specific approach to food security in the prehistoric/historic past, which would allow more direct hypothesis-testing of the thrifty genotype and other evolutionary models.

Finally, our results may have implications for 'fetal origin' etiological models of diabetes. It is becoming increasingly clear that our species is remarkably flexible in our ability to adapt physiologically (via phenotypic and developmental plasticity) to highly variable nutritional environments, beginning in fetal life and continuing throughout the life cycle. This may mean that thrifty genetic adaptations to these environments play significantly less of a role, and physiological adaptations a much greater one, than once believed.

In our current work, we have identified and are examining three events in the history of the native peoples of the Sonoran Desert that could have produced selective forces sufficient enough to telescope "thrifty" genes in these populations. First, the earliest human migrations into the Americas provide abundant evidence for genetic drift American Indians, but these genetic markers are independent of metabolic controls. Second, the transition to agriculture in the Sonora Desert could create selections for metabolic responses to periods of food insecurity, but archaeological and skeletal evidence indicates that nutrition and health was excellent. Third, the European entrance into the New World, and later the Sonoran Desert, caused massive die-offs that could have created episodes of selection and/or drift, but these forces were created by epidemic and not metabolic diseases. There is evidence however, for periods of severe nutritional stress associated with reservation policies, a loss of traditional lifeway, and the possibility that plastic physiological responses to these stresses formed a positive feedback cycle that created a metabolic epidemic among subsequent generations.