Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Thrifty vs Drifty Gene Theory of Obesity

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 society—the ‘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 hypothesis—particularly 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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

References

  1. Neel JV . Diabetes mellitus a ‘thrifty’ genotype rendered detrimental by ‘progress’? Am J Hum Genet 1962; 14: 352–353.

    Google Scholar 

  2. Maes HH, Neale MC, Eaves LJ . Genetic and environmental factors in relative body weight and human adiposity. Behav Genet 1997; 27: 325–351.

    Article  CAS  Google Scholar 

  3. Perusse L, Chagnon YC, Rice T, Rao DC, Bouchard C . Genetic epidemiology and molecular genetics of obesity: results from the Quebec Family Study. Med Sci 1998; 14: 914–924.

    Google Scholar 

  4. Barsh GS, Farooqi IS, O'Rahilly S . Genetics of body-weight regulation. Nature 2000; 404: 644–651.

    Article  CAS  Google Scholar 

  5. Eaton SB, Konner M, Shostak M . Stone agers in the fast lane: chronic degenerative diseases in evolutionary perspective. Am J Med 1988; 84: 739–749.

    Article  CAS  Google Scholar 

  6. Lev-Ran A . Thrifty genotype: how applicable is it to obesity and type 2 diabetes? Diabetes Rev 1999; 7: 1–22.

    Google Scholar 

  7. Lev-Ran A . Human obesity: an evolutionary approach to understanding our bulging waistline. Diabetes Metab Res Rev 2001; 17: 347–362.

    Article  CAS  Google Scholar 

  8. Campbell BC, Cajigal A . Diabetes: energetics, development and human evolution. Med Hypotheses 2001; 57: 64–67.

    Article  CAS  Google Scholar 

  9. Prentice AM . Obesity and its potential mechanistic basis. Br Med Bull 2001; 60: 51–67.

    Article  CAS  Google Scholar 

  10. Ravussin E . Cellular sensors of feast and famine. J Clin Invest 2002; 109: 1537–1540.

    Article  CAS  Google Scholar 

  11. Diamond J . The double puzzle of diabetes. Nature 2003; 423: 599–602.

    Article  CAS  Google Scholar 

  12. Chakravarthy MV, Booth FW . Eating, exercise, and ‘thrifty’ genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases. J Appl Physiol 2004; 96: 3–10.

    Article  Google Scholar 

  13. Wilkin TJ, Voss LD . Metabolic syndrome: maladaptation to a modern world. J R Soc Med 2004; 97: 511–520.

    Article  Google Scholar 

  14. Scott EM, Grant PJ . Neel revisited: the adipocyte, seasonality and type 2 diabetes. Diabetologia 2006; 49: 1462–1466.

    Article  CAS  Google Scholar 

  15. Prentice AM, Rayco-Solon P, Moore SE . Insights from the developing world: thrifty genotypes and thrifty phenotypes. Proc Nutr Soc 2005; 64: 153–161.

    Article  CAS  Google Scholar 

  16. Prentice AM . Early influences on human energy regulation: thrifty genotypes and thrifty phenotypes. Physiol Behav 2005a; 86: 640–645.

    Article  CAS  Google Scholar 

  17. Prentice AM . Starvation in humans: evolutionary background and contemporary implications. Mech Ageing Dev 2005b; 126: 976–981.

    Article  Google Scholar 

  18. Wells JCK . The evolution of human fatness and susceptibility to obesity: an ethological approach. Biol Rev Camb Philos Soc 2006; 81: 183–205.

    Article  Google Scholar 

  19. Eknoyan G . A history of obesity, or how what was good became ugly and then bad. Adv Chronic Kidney Dis 2006; 13: 421–427.

    Article  Google Scholar 

  20. Watnick S . Obesity: a problem of Darwinian proportions? Adv Chronic Kidney Dis 2006; 13: 428–432.

    Article  Google Scholar 

  21. Speakman JR . Obesity: the integrated roles of environment and genetics. J Nutr 2004; 134: 2090S–2105S.

    Article  CAS  Google Scholar 

  22. Speakman JR . The genetics of obesity: five fundamental problems with the famine hypothesis. In: Fantuzzi G, Mazzone T (eds). Adipose Tissue and Adipokines in Health and Disease. Humana Press: Totowa, NJ, 2006a. pp 193–208.

    Google Scholar 

  23. Speakman JR . ‘Thrifty genes’ for obesity and the metabolic syndrome: time to call off the search? Diab Vasc Dis Res 2006b; 3: 7–11.

    Article  Google Scholar 

  24. Speakman JR . A novel non-adaptive scenario explaining the genetic pre-disposition to obesity: the ‘predation release’ hypothesis. Cell Metab 2007; 6: 5–12.

    Article  CAS  Google Scholar 

  25. Haldane JBS . The Causes of Evolution. Princeton University Press: Princeton, 1932.

    Google Scholar 

  26. Flegal KM . Epidemiologic aspects of overweight and obesity in the United States. Physiol Behav 2005; 86: 599–602.

    Article  CAS  Google Scholar 

  27. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM . Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 2006; 295: 1549–1555.

    Article  CAS  Google Scholar 

  28. Flegal KM, Troiano RP . Changes in the distribution of body mass index of adults and children in the US population. Int J Obes 2000; 24: 807–818.

    Article  CAS  Google Scholar 

  29. Keys A, Brozek J, Henschel A, Mickelsen O, Taylor HL . The Biology of Human Starvation. University of Minnesota Press: Minnesota, 1950.

    Book  Google Scholar 

  30. Wrigley EA, Schofield R . The Population History of England, 1541–1871. Harvard University Press: Cambridge, MA, 1981.

    Google Scholar 

  31. Dupaquier J . L’analyse statistique des crises de mortalitie. In: Charbonneau H, LaRose A (eds). The Great Mortalities. Ordina: Liege, 1979, pp 83–112.

    Google Scholar 

  32. Ho PT . Studies on the population of China 1368–1953. Harvard University Press: Cambridge, MA, 1959.

    Book  Google Scholar 

  33. St Clair D, Xu MQ, Wang P, Yu YQ, Fang YR, Zhang F et al. Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959–1961. JAMA 2003; 294: 557–562.

    Article  Google Scholar 

  34. Mokyr J, Grada CO . Famine disease and famine mortality: lessons form Ireland, 1845–1850. Centre for Economic Research Working Paper 99/12. University College: Dublin, 1999.

    Google Scholar 

  35. Watkins SC, Menken J . Famines in historical perspective. Popul Dev Rev 1985; 11: 647–675.

    Article  Google Scholar 

  36. Lindtjorn B . Famine in southern Ethiopia, 1985–86: population structure, nutritional state and incidence of death. BMJ 1990; 301: 1123–1127.

    Article  CAS  Google Scholar 

  37. Alemu T, Lindtjorn B . Physical-activity, illness and nutritional-status among adults in a rural Ethiopian community. Int J Epidemiol 1995; 24: 977–983.

    Article  CAS  Google Scholar 

  38. Hionidou V . Why do people die in famines? Evidence from three island populations. Population Studies. J Demogr 2002; 56: 65–80.

    Google Scholar 

  39. Tauxe RV, Holmberg SD, Dodin A, Wells JV, Blake PA . Epidemic cholera in Mali—high mortality and multiple routes of transmission in a famine area. Epidemiol Infect 1988; 100: 279–289.

    Article  CAS  Google Scholar 

  40. Raoult D, Woodward T, Dumler JS . The history of epidemic typhus. Infect Dis Clin North Am 2004; 18: 127–130.

    Article  Google Scholar 

  41. Lindtjorn B, Alemu T, Bjorvatn B . Nutritional status and risk of infection among Ethiopian children. J Trop Pediatr 1993; 39: 76–82.

    Article  CAS  Google Scholar 

  42. Collins S, Myatt M . Short-term prognosis in severe adult and adolescent malnutrition during famine—use of a simple prognostic model based on counting clinical signs. JAMA 2000; 284: 621–626.

    Article  CAS  Google Scholar 

  43. Sen A . Poverty and Famines: an Essay on Entitlement and Deprivation. Clarendon Press: Oxford, 1981.

    Google Scholar 

  44. Chen LC, Chowdhury AKMA . The dynamics of contemporary famine. In: Mexico International Population Conference (Volume 1) Liege International Union for the Scientific Study of Population: Leige, Belgium, 1977, pp 409–426.

    Google Scholar 

  45. Toole MJ, Waldman RJ . An analysis of mortality trends among refugee populations in Somalia, Sudan, and Thailand. Bull World Health Organ 1988; 66: 237–247.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Menken J, Campbell C . Forum: on the demography of South Asian famines. Health Transit Rev 1992; 2: 91–108.

    Google Scholar 

  47. Neumayer E, Plumper T . The gendered nature of natural disasters: the impact of catastrophic events on the gender gap in life expectancy, 1981–2002. Ann Assoc Am Geogr 2007; 97: 551–566.

    Article  Google Scholar 

  48. Frisch RE . The right weight-body fat menarche and fertility. Proc Nut Soc 1994; 53: 113–129.

    Article  CAS  Google Scholar 

  49. Frisch RE . Critical fat. Science 1993; 261: 1103–1104.

    Article  CAS  Google Scholar 

  50. Frisch RE . Body weight, body fat and ovulation. Trends Endocrinol Metab 1991; 2: 191–197.

    Article  CAS  Google Scholar 

  51. Stein ZA . Famine and Human Development: the Dutch Hunger Winter of 1944–45. Oxford University Press: Oxford, 1975.

    Google Scholar 

  52. Wade GN, Schneider JE, Li HY . Control of fertility by metabolic cues. Am J Physiol 1996; 33: E1–E19.

    Google Scholar 

  53. Schneider JE, Zhou D, Blum RM . Leptin and metabolic control of reproduction. Horm Behav 2000; 37: 306–326.

    Article  CAS  Google Scholar 

  54. Johnston S, Grune T, Bell L, Murray S, Souter D, Erwin S et al. Having it all—historical energy intakes do not generate the anticipated trade-offs in fecundity. Proc R Soc Lond B Biol Sci 2006; 273: 1369–1374.

    Article  CAS  Google Scholar 

  55. Pasquali R, Gambineri A, Pogotto U . The impact of obesity on reproduction in women with polycystic ovary syndrome. BJOG 2006; 113: 1148–1159.

    Article  CAS  Google Scholar 

  56. Pasquali R . Metabolic effects of obesity on reproduction. Reprod Biomed Online 2006; 12: 542–551.

    Article  CAS  Google Scholar 

  57. Barber TM, McCarthy MI, Wass JAH, Franks S . Obesity and polycystic ovary syndrome. Clin Endocrinol 2006; 65: 137–145.

    Article  CAS  Google Scholar 

  58. Norman RJ, Clark AM . Obesity and reproductive disorders: a review. Reprod Fertil Dev 1998; 10: 55–63.

    Article  CAS  Google Scholar 

  59. Bribiescas RG . Serum leptin levels and anthropometric correlates in ache Amerindians of eastern Paraguay. Am J Phys Anthropol 2001; 115: 297–303.

    Article  CAS  Google Scholar 

  60. Campbell B, O'Rourke MT, Lipson SF . Salivary testosterone and body composition among Ariaal males. Am J Hum Biol 2003; 15: 697–708.

    Article  Google Scholar 

  61. Kesteloot H et al. Serum lipid levels in a Pygmy and Bantu population sample from Cameroon. Nutr Metab Cardiovasc Dis 1997; 7: 383–387.

    Google Scholar 

  62. Kirchengast S . Weight status of adult! Kung San and Kavango people from northern Namibia. Ann Hum Biol 1998; 25: 541–551.

    Article  CAS  Google Scholar 

  63. Odea K . Cardiovascular-disease risk-factors in Australian aborigines. Clin Exp Pharmacol Physiol 1991; 18: 85–88.

    Article  CAS  Google Scholar 

  64. Helmchen LA, Henderson RM . Changes in the distribution of body mass index of white US men, 1890–2000. Ann Hum Biol 2004; 31: 174–181.

    Article  CAS  Google Scholar 

  65. Neel JV . Update to the study of natural selection in primitive and civilized human populations. Hum Biol 1989; 61: 811–823.

    Google Scholar 

  66. Kimura M . The Neutral Theory of Molecular Evolution. Cambridge University press: Cambridge, 1986.

    Google Scholar 

  67. El Bakry HA, Plunket SS, Bartness TJ . Photoperiod but not high fat diet alters body fat in Shaw's jird. Physiol Behav 1999; 68: 87–91.

    Article  CAS  Google Scholar 

  68. Peacock W, Speakman JR . Effect of high-fat diet on body mass and energy balance in the bank vole. Physiol Behav 2001; 74: 65–70.

    Article  CAS  Google Scholar 

  69. Krol E, Redman P, Thomson PJ, Williams R, Mayer C, Mercer JG et al. Effect of photoperiod on body mass, food intake and body composition in the field vole, Microtus agrestis. J Exp Biol 2005; 208: 571–584.

    Article  CAS  Google Scholar 

  70. Zurlo F, Lillioja S, Esposito-del Puente A, Nyombe BL, Raz I, Saad MF et al. Low ratio of fat to carbohydrate oxidation as predictor of weight-gain—study of 24-h RQ. Am J Physiol 1990; 259: E650–E657.

    CAS  PubMed  Google Scholar 

  71. Marra M, Scalfi L, Covino A, Esposito-del Puente A, Contaldo F . Fasting respiratory quotient as a predictor of weight changes in non-obese women. Int J Obes 1998; 22: 601–603.

    Article  CAS  Google Scholar 

  72. Marra M, Scalfi L, Contaldo F, Pasanisi F . Fasting respiratory quotient as a predictor of long-term weight changes in non-obese women. Ann Nutr Metab 2004; 48: 189–192.

    Article  CAS  Google Scholar 

  73. Frisancho AR . Reduced rate of fat oxidation: a metabolic pathway to obesity in the developing nations. Am J Hum Biol 2003; 15: 522–532.

    Article  Google Scholar 

  74. Kunz I, Schorr U, Rommling K, Klaus S, Sharma AM . Habitual fat intake and basal fat oxidation in obese and non-obese Caucasians. Int J Obes 2002; 26: 150–156.

    Article  CAS  Google Scholar 

  75. Ravussin E, Gautier JF . Metabolic predictors of weight gain. Int J Obes 1999; 23: 37–41.

    Article  Google Scholar 

  76. Tataranni PA . From physiology to neuroendocrinology: a reappraisal of risk factors of body weight gain in humans. Diabetes Metab 1998; 24: 108–115.

    CAS  PubMed  Google Scholar 

  77. Chang S, Graham B, Yakuba F, Lin D, Peters JC, Hill JO . Metabolic differences between obesity prone and obesity resistant rats. Am J Physiol 1990; 259: R1103–R1110.

    CAS  PubMed  Google Scholar 

  78. Ji H, Friedman MI . Reduced capacity for fatty acid oxidation in rats with inherited susceptibility to diet-induced obesity. Metab Clin Exp 2007; 56: 1124–1130.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I am grateful to many people for interesting discussions and e-mail exchanges about these ideas. In particular, I acknowledge Eric Ravussin, Hans Rudi Berthoud, Ela Krol, David Allison, Andrew Prentice, Aryeh Stein, Leanne Redman and Marc Reitman for their challenging questions, helpful comments and pointers to useful data. Finally, I am grateful to Ian Macdonald and Richard Atkinson for the invitation to write this piece.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J R Speakman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Speakman, J. Thrifty genes for obesity, an attractive but flawed idea, and an alternative perspective: the ‘drifty gene’ hypothesis. Int J Obes 32, 1611–1617 (2008). https://doi.org/10.1038/ijo.2008.161

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2008.161

Keywords

This article is cited by

Search

Quick links