The Thrifty Gene Hypothesis
James Neel-1962
Genes that predispose us to obesity were advantageous in early human history when starvation was an issue.
Early Humans went through cycles of feast and famine and thus more efficient at food storage and utilization were more likely to survive and reproduce during famine.
Feast-Famine Cycle
Physical Activity Chakravarthy and Booth (2004)
Physical activity was as important as food related adaptations
Early humans went through Physical-Activity cycle that mimics feast-famine cycle physiologically.
People who were more capable physically of surviving the hunt or gathering food, would survive and pass down their genetics
Physiological response to Feasting and Recovery from Exercise, as well as to Famine and Exercise are remarkably similar
Combined these similar processes provide a much larger genetic drive for “thrifty genes”
Chakravarthy, M. V. & Booth, F. W. (2004). Eating, exercise, and “thrifty” genotypes: connecting the dots toward and evolutionary understanding of modern chronic diseases. J Appl Physiol, 96(1), 3–10.
Feast-Famine and Physical Activity Cycle Model
Chakravarthy, M. V. & Booth, F. W. (2004). Eating, exercise, and “thrifty” genotypes: connecting the dots toward and evolutionary understanding of modern chronic diseases. J Appl Physiol, 96(1), 3–10.
Modern Problem
Chakravarthy, M. V. & Booth, F. W. (2004). Eating, exercise, and “thrifty” genotypes: connecting the dots toward and evolutionary understanding of modern chronic diseases. J Appl Physiol, 96(1), 3–10.
Critiques and Problems
Complex-Not just one gene
The Natural Selection Driver Death
Minor famine’s occurred frequently throughout history, but severe Famines much less frequent (~150years)
Birth During even minor
famine’s, reproduction is reduced because lower body fat intake negatively impacts reproduction
Prentice, A. M., Hennig, B. J. & Fulford, A. J. (2008). Evolutionary origins of the obesity epidemic: natural selection of thrifty genes or genetic drift following predation release? International Journal of Obesity, 32, 1607–1610.
When did genetic changes start? Hunter-Gather era
Rate of selection calculations show that 99% of us would have the thrifty genes if started back then.(Speakman, 2008).
Why aren’t we all fat? Thrifty genes not meant to make fat, but rather
enhance fuel storage, utilization, and efficiency. Agricultural era
Genes related to glucose and fat metabolism have been positively selected within the last 10,000 years (Voight, 2006)
We all have thrifty genes?
Stoger Thrifty phenotype hypothesis because energy efficiency and fitness
was essential to early man, “unthrifty” genes never were allowed to become established
Endurance hypothesis (Brambley and Lieberman, 2004)
If we all have thrifty genes, then why is obesity seemingly more heritable in certain groups like the Pima Indians?
Thrifty Epigenome: The missing link? Old theory: Have the gene or don’t New theory: The function (the degree of
expression) of the gene matters Epigenetics- manipulates how the gene
functions (whether it’s turned on/off, and the degree of transcription)
Genome=Hardware Epigenome=Software
Most susceptible to change while fetus is in development
Genetic imprinting- can be passed on for a couple generations
Short term adaptation to the environment
Epigenome adapts to the predicted environment when in utero. Mother experiences famine,
epigenome overeacts and up regulates genes for food storage and utilization
Mismatch When
predicted environment does NOT equal actual environment disease (obesity) occurs
Godfrey, K. M., Lillycrop, K. A., Burdge, G. C., Gluckman, P. D. & Hanson, M. A. (2007). Epigenetic mechanism and the mismatch concept of the developmental origins of health and disease. Pediatric Research, 61(5), 5–10.
Evidence
Ravelli et al. (1976) Obesity much higher in individuals
whose mother went through famine during pregnancy
Dong et al. 2005) Found Genetic imprinting in obesity
related genes
Conclusion Obesity is a polygenic problem
Very complex- not a single gene issue It not only matters whether one has a
combination of genes, but how they function. Eaton et al. (1988) put it best when they said
that we have “ ‘Stone Age’ genes and ‘Space Age’ circumstances.”
Physical Activity and food were likely intricately linked from the start of mankind and it’s a mistake to consider one and not the other.
References Bramble, D. M. & Lieberman, D. E. (2004). Endurance running and the evolution of Homo. Nature, 432, 345–352. Bribeescas, R. G. (2001). Serum leptin levels and anthropmetric correlates in ache Amerindians of eastern
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and evolutionary understanding of modern chronic diseases. J Appl Physiol, 96(1), 3–10. Dong, C., Lie, W. D., Geller, F., Lei, L., Li, D., Gorlova, O. Y., Hebebrand, J., Amos, C. I., Nichols, R. D. & Price, R. A.
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Godfrey, K. M., Lillycrop, K. A., Burdge, G. C., Gluckman, P. D. & Hanson, M. A. (2007). Epigenetic mechanism and the mismatch concept of the developmental origins of health and disease. Pediatric Research, 61(5), 5–10.
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Neel, J. V. (1962). Diabetes mellitus a ‘thrifty’ genotype rendered detrimental by ‘progress’? Am J Hum Genet, 14, 352–353.
Prentice, A. M., Hennig, B. J. & Fulford, A. J. (2008). Evolutionary origins of the obesity epidemic: natural selection of thrifty genes or genetic drift following predation release? Internationa Journal of Obesity, 32, 1607–1610.
Prentice, A. M. (2005). Starvation in humans: evolutionary background and contemporary implications. Mech Ageing Dec, 126, 976–981.
Ravelli, G. P., Stein, Z. A. & Susser, M. W. (1976). Obesity in young men after famine exposure in utero and early infancy. N Eng J Med, 295, 349–353.
Speakman, J. R. (2008). Thrifty genes for obesity, an attractive but flawed idea, and an alternative perspective: the ‘drifty gene’ hypothesis. International Journal of Obesity, 32, 1611–1617.
Stoger, R. (2008). The thrifty epigenotype: an acquired and heritable predisposition for obesity and diabetes? BioEssays, 30(2), 156–166.
Voight, B. F., Kudaravalli, S., Wen, X. & Pritchard, J. K. (2006). A map of recent positive selection in the human genome. PLoS Biol, 72.