Tight Jeans? Don’t Blame Your Genes

Lucinda Peng | lucinda.peng@yale.edu January 24, 2017

Tight Jeans? Don’t Blame Your Genes

The prevalence of obesity and Type 2 diabetes has been increasing for at least fifty years. Attempting to explain this trend from an evolutionary perspective, researchers developed the “thrifty gene hypothesis”: the idea that evolution selected for genes that promote fat storage as an evolutionary advantage during famines.

The hypothesis originated in 1962, when James Neel proposed that modern living conditions had created an evolutionary mismatch, which occurs when genes that once were advantageous become deleterious in a new environment. He concluded that this mismatch had contributed to an increase in Type 2 diabetes, and his hypothesis was the first widely discussed idea on the subject. However, in 1989 Neel reviewed his own work and realized that his hypothesis was probably incorrect, for famines occurred too infrequently to have generated significant selection pressure. Since then, the theory has been put aside in favor of other hypotheses, and the new results discussed below solidify that move.

Guanlin Wang and John Speakman of the Chinese Academy of Sciences found genetic evidence opposing the thrifty gene hypothesis. They examined 115 single nucleotide polymorphisms (SNPs), or common genetic mutations, that had previously been found to be correlated with obesity. They used genomes from a database compiled by the 1000 Genomes Project, an international collaboration to document genetic variability among different ethnicities, to ensure that effects of specific subpopulations did not influence their results. When Wang and Speakman analyzed the SNPs associated with a higher body mass index (BMI) in obese and control populations, they found no significant selection for these genes, suggesting that evolution has not selected for obesity. In fact, of the nine genes associated with BMI, five of them had decreased, rather than increased fat storage. Their discovery is not consistent with the genetic basis of the thrifty gene hypothesis, increasing the plausibility of other theories about the underlying causes of obesity. Dr. Stephen Stearns, Yale professor of Ecology and Evolutionary Biology, cites two other hypotheses to replace the thrifty gene hypothesis: the thrifty phenotype and the hygiene hypotheses.

Hales and Baker proposed the thrifty phenotype hypothesis in 1992, suggesting that the body uses information from the environment early in life to predict its needs for the future environment. These environmental conditions can induce epigenetic changes, or nongenetic mechanisms that affect phenotypic (observable) traits. They found that babies born during the Dutch Hunger Winter, a six-month food blockade by the Germans in the Netherlands, were more prone to insulin resistance due to nutritional deficit in the womb. Insulin promotes the absorption of sugar from blood into tissues, but under starvation conditions, nonessential tissues become less responsive to insulin so that the brain can receive enough sugar. When the Germans left, food was abundant, so the environment that the baby was prepared for did not match the environment it was born into. As a result, the people born in this period were more prone to diabetes and other diseases. “This trend can be observed under normal circumstances too, as birth weight is a good predictor of risk of diseases later in life,” said Dr. Stearns. The thrifty phenotype hypothesis addresses a major problem from the thrifty genotype hypothesis. If there had been continued, strong positive selection for increased fat storage, all humans would be obese because these genes would be fixed, or permanently added to the human genome. In contrast, with “thrifty phenotypes,” epigenetic factors are affected by the environment and can vary among people.

The hygiene hypothesis relates the gut microbiota to metabolic diseases. The gut microbiota is composed of bacteria that help to break down macromolecules and absorb nutrients; it is sensitive to environmental stimuli. For example, babies born by C-section rather than vaginal birth have different microbiota because they were not exposed to the bacteria in their mother’s birth canal, and being breastfed or taking antibiotics can also affect a baby’s gut microbiota. These changes have been shown to affect their risk of obesity, insulin resistance, and Type 2 diabetes.

With a lack of genetic evidence to support the claim that humans evolved to better store fat, the thrifty phenotype and hygiene hypotheses are now favored to replace the thrifty genotype hypothesis. Wang and Speakman’s paper provides more concrete evidence to refute the thrifty gene hypothesis, supporting what many scientists already believed. Because the thrifty phenotype and hygiene hypotheses explain why metabolic diseases can be inherited but are also heavily influenced by the environment, they provide a more robust explanation for the rise in obesity and Type 2 diabetes.