Thrifty genes for obesity, an attractive but flawed idea, and an alternative perspective: the ‘drifty gene’ hypothesis

Abstract

Almost 50 years ago Neel proposed a hypothesis to explain the prevalence of obesity and diabetes in modern societyFthe 'thrifty gene' hypothesis. The fundamental basis of the hypothesis was that, in our early evolutionary history, genes, that promoted efficient fat deposition would have been advantageous because they allowed their holders to survive at periods of famine. In modern society, such genes are disadvantageous because they promote fat deposition in preparation for a famine that never comes, and the result is widespread obesity and diabetes. In recent years I, and others, have questioned some of the fundamental assumptions of this hypothesisFparticularly focusing on whether differential survival of lean against obese in famines provides sufficient selective pressure for the spread of so-called 'thrifty genes'. These arguments have been criticized because famines not only affect survival but also fecundity, and obese people would be expected to sustain fecundity longer in the face of food shortages. In this paper, I show that the reduced fecundity argument is flawed because famines are almost universally followed by periods of enhanced fecundity, which offsets the decline observed during the famine itself. The net effect of famines on fecundity is consequently insufficient to rescue the thrifty gene idea. Elsewhere, I have suggested an alternative scenario that subsections of the population have a genetic predisposition to obesity due to an absence of selection, combined with genetic drift. The scenario presented earlier was based on evidence from prehistory concerning the release of our ancestors from heavy predation pressure around 2 million years ago. I suggest here that this is one of a number of potential scenarios based on random genetic drift that may explain the specific aetiology of the obesity epidemic. Together, these alternatives, based on central notion that genetic drift rather than positive selection was a dominant factor, may be called the 'drifty gene' hypothesis.

Worldwide spatial genetic structure of angiotensin-converting enzyme gene: a new evolutionary ecological evidence for the thrifty genotype hypothesis

“…However, in contemporary societies, as food is usually available in unlimited amounts, the 'thrifty genotype' no longer provides a survival advantage, but renders its owners more susceptible to obesity and diabetes. 5 Although variants of this hypothesis have formed the topic of vigorous debate, [6][7][8][9][10] there are many researches that tend to support this hypothesis, not only in epidemiology [11][12][13] but also in population genetics or evolutionary ecology. 4,14,15 One of the problems of using the 'thrifty gene' concept is that most individuals associate it with a metabolic trait related to a frugal utilization of fuel, which indeed was Neel's (1962) first intention.…”

Thrift: a guide to thrifty genes, thrifty phenotypes and thrifty norms

“…Frequent reference is made to 'thrifty genes' or 'thrifty phenotypes', illustrated, for example, by the recent debate between Speakman and Prentice and colleagues regarding utility of the concept of thrifty genes. [1][2][3][4] However, recent progress in our understanding of human evolution, both in terms of genetic evolution and components of plasticity, prompts a reappraisal of how thrift is generated and transferred within and between generations. The aim of this article is to clarify the concept of thrift and the ways in which, and time scales over which, this metabolic strategy can manifest in organisms.…”

Energy balance and obesity: a UK perspective on the gluttonyv.sloth debate

“…Although genetic studies should reveal new insights into the biological pathways that underlie weight gain and body fat accumulation, and may eventually explain why humans are better able to defend against weight loss than against weight gain, to date progress in this direction appears to be slow. This has allowed a range of views and interpretations to develop, not only in relation to the more esoteric questions, such as the evolutionary origins of human susceptibility to obesogenic environments and diets (15,16) , but also over questions relating to basic issues such as the relative importance of increasing EI or decreasing EE as the primary driver of weight gain. One approach to the debate is to recognise that such debates are over-simplistic.…”