The Ultimate Trade-off: Genes, Environment, and Why We Crave Twinkies

Last week in the Spittoon we reported on a new study that identified an interesting genetic trade-off — a genetic variant known that has one effect on a person’s vulnerability to malaria, and the opposite on susceptibility to HIV infection. The “Duffy negative” version of the gene, which is common among Africans and African Americans, appears to protect a person against malaria but increases vulnerability to infection by HIV.

As it turns out, Duffy is not the only example of a genetic trade-off in humans.  There are many instances of genetic variation throughout the human genome that offer both genetic advantages and disadvantages to their carriers.  Here are some of the most interesting:

1.    Sickle Cell Anemia vs. Malaria

Sickle cell anemia is caused by a genetic mutation that alters the shape of an individual’s red blood cells.  This mutation, called Hbs, causes red blood cells to take on a sickle-shape, as opposed to the normal round shape.  The sickle-shaped cells then get stuck in the veins and arteries, causing tremendous pain and discomfort.  Sickle cell anemia is recessively inherited, meaning that someone must inherit the Hbs mutation from both parents in order to have the disease.

Malaria is a disease that kills between 1 and 3 million people worldwide each year, mainly in the tropics.  After scientists noticed similarities between the geographic distribution of sickle cell anemia and malaria, they began to wonder if there was some sort of connection between the two.



Experiments soon confirmed that sickle cell anemia is a sort of genetic Faustian bargain. Recall that individuals with two copies of Hbs suffer from sickle cell anemia, but people with only one copy of the mutation do not.  They do however, display a resistance to malaria compared with people who have no copies of Hbs.  Occasionally, a pair of malaria-resistant parents will both pass Hbs — and thus sickle cell anemia — to their child. But overall, having only one copy improved the survival rate in human history so much that the Hbs mutation continues to exist in in spite of the disease burden it causes.

2.    Hereditary Hemochromatosis vs. Iron Deficiency

Hereditary hemochromatosis (HH) is a genetic condition in which the body absorbs too much iron from the diet.  This leads to the toxic build-up of iron in the tissues of major organs such as the liver and heart.  Without treatment, HH can lead to organ failure.

Genetic studies have found that HH, like sickle-cell, is a recessive trait. It appears to have evolved about 1,400 years ago, probably in western Europe, at a time when people ate mostly cereal grains — which are very low in iron. Because having some amount of iron in the diet is essential to maintain normal body functions, this was a serious problem.  

During this time period, the ability to store extra iron in the body would have been helpful.  Individuals with HH could take iron from foods when it was available, and then store it in the organ tissues, dipping into those reserves when the supply of iron-rich foods was low.  Today, however, iron is much more abundant. It is an excess of iron, not a lack of it, that threatens the health of people with HH.

3.    The Paleolithic Diet vs. Obesity

Why is it that humans crave the very foods that are unhealthy?  Why do we prefer donuts and candy to celery and spinach?  Like hereditary hemochromatosis, the source of this cruel irony lies in the history of our species.

The human brain is a very expensive organ to maintain.  It requires a lot of energy to keep all the synapses working correctly, and simply feasting on celery would not do the trick.  Hundreds of thousands of years ago, our ancestors began eating meat as a way to get the required energy their brains needed.  Meat is high in the energy that humans needed to survive, and also in long-chain polyunsaturated fats, which are essential to maintenance of brain tissue.  Bone marrow, the fatty substance inside long bones, is also high in fat and calories, and was thus another prized item in our ancestors’ early diet.  

Because foods high in fat and calories were so important to our ancestors, they would have searched them out and evolved a natural preference for them.  Their bodies would have evolved to store any excess fat, in case there were was a long hiatus until the next piece of meat or bone marrow came their way. 

This ‘thrifty’ metabolic approach to fat has persisted to the present day, despite drastic changes in the way we feed ourselves.  Now, instead of searching constantly for food we have seemingly unlimited access to Twinkies, beer and other high-calorie delights.  But our bodies are still storing the excess fat.

The genetics of obesity are complicated, and by no means can they be fully explained by our ancestors’ diet. But the dramatic change in the human diet since the Stone Age does help explain our cravings from an evolutionary perspective.

Variations in the human genome are full of examples such as these: genetic mutations that are beneficial in some ways but harmful in others, or that used to be beneficial, but now result in an increased waistline.  Understanding these genetic ‘trade-offs’ is helpful to understanding the history of the human genome, and could be helpful in tackling conditions such as sickle-cell anemia, hereditary hemochromatosis, obesity and many others.


Return to top