YSM Issue 90.1

COUNTERPOINT
TIGHT JEANS? DON’T BLAME YOUR GENES
►BY LUCINDA PENG
The prevalence of obesity and Type 2 diabetes has been increasing for
at least 50 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
IMAGE COURTESY OF WIKIMEDIA COMMONS
►Calorie dense junk food has contributed to the rise of type 2
diabetes and obesity.
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 a 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 the risk of
being affected by 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.
34 Yale Scientific Magazine December 2016 www.yalescientific.org