Photo by Trevor Bair. Via Creative Commons
Photo by Trevor Bair. Via Creative Commons

What To Expect When You’re Expecting, By Charles Darwin

A few years back, a team of scientists combed through the records for a million births in New York City. They noted women who had developed gestational diabetes during their pregnancy, and they also noted the women’s ethnic backgrounds. Women of European descent, the scientists found, had the lowest risk for gestational diabetes, with only 3.6% of them developing the disorder. African Americans had a somewhat higher risk of 4.3%. South Asian women, by contrast, face a far higher risk of 14.3%, with Bangladeshis running the highest risk of all: one out of every five Bangladeshi mothers in New York developed gestational diabetes.

Another risk that pregnant women run is giving birth to babies with deformed spinal columns.  The pattern of these so called neural-tube defects is quite different from that of gestational diabetes. Dark-skinned women–in Africa, as well as Asia and Australia–are at low risk, while European women are the ones more likely to encounter this trouble.

A team of three Harvard biologists–Elizabeth Brown, Maryellen Ruvolo, and Pardis Sabeti–think that there’s a coherent explanation for these patterns, and many of the other puzzling features about pregnancy. They are the result of evolution.

In a paper to be published in Trends in Genetics, the researchers argue that pregnancy has been one of the most important targets of natural selection in all of human biology. Mutations that raise the success rate of pregnancies let women have more offspring, who can spread their genes throughout a population. Pregnancy has also posed huge risks to women that could threaten their own survival. A woman’s reproductive success depends not just on her newborn child surviving, but on her own survival as well.

Evolution was shaping pregnancy long before our species walked the Earth, but it continued to do so even in the past few thousand years. And the traits that help women out the most in one part of the world don’t necessarily help in another.

Local adaptations may account for some of the differences in pregnancy-related troubles seen in women around the world. Take gestational diabetes. Bad genes can make women more vulnerable to diabetes. But the food they eat can also raise their risk–specifically, diets rich in carbohydrates. It turns out that the women with the lowest rates of gestational diabetes come from parts of the world where people traditionally have a diet that’s the highest risk for the disease.

This may be an evolutionary impact of the Agricultural Revolution. When Europeans shifted from hunting and gathering to farming, they boosted the sugar in their diet by eating wheat and drinking milk. We know that mutations that enabled them to digest milk efficiently as adults were strongly favored by natural selection. Digesting milk may have been especially important for successful pregnancies. The calcium could have helped build a strong pelvis to make childbirth easier. And pregnant women drinking milk could use its calorie-rich fat to nourish their fetuses.

Women nourish their fetuses by raising the level of sugar in their blood. That’s a dangerous game, because it threatens to throw off their own delicate balance between sugar and insulin. If that balance gets out of whack, women may suffer gestational diabetes. The Harvard researchers suggest that the shift to high-carb agriculture in Europe led to more women dying of gestational diabetes. Women with mutations that lowered their blood sugar level during pregnancy were favored by natural selection. And today, European women enjoy the benefits of that suffering: a low risk of gestational diabetes.

A woman in Bangladesh has a very different history behind her. Her ancestors ate fish, unprocessed rice, and other foods with modest levels of carbohydrates. In that environment, women with mutations that increased their blood sugar during pregnancy might have had healthier children than women without them.  Throw those genes into a modern Western city, and trouble looms. Women with low-sugar genes are now drinking soda and eating bread, ice cream, and lots of other food loaded in carbs. They don’t have the evolved defenses to keep them from developing gestational diabetes.

Another evolutionary process could explain neural tube defects. In order for a baby’s spine to form properly, it needs a nutrient called folate. That’s why doctors are constantly nagging pregnant women to eat folate-rich food or take supplements, so that they can then pass some of it on to their fetus.

It turns out that the body stores folate in the blood vessels in the skin, from where it can then be dispensed to a fetus. Close to the surface of the body, the folate is vulnerable to ultraviolet rays, which can destroy it. Dark-skinned women can shield their folate with their pigment. Lighter-skinned women have fewer defenses.

Here again, evolution can explain the difference between women from different parts of the world. The skin needs sunlight to generate vitamin D. When humans moved to northern regions of the world, the sun was so low in the sky that there was an advantage to losing some of their pigmentation, allowing more sunlight in. Unfortunately, the ability to make vitamin D in low sunlight came at a price–a price that women today still pay.

Sunlight isn’t the only factor that’s different for women around the world. The altitude is as well. And for women living in mountains, pregnancy poses a risk that lowland women don’t have to worry about: low oxygen. Without enough oxygen to meet the demands of rearing a fetus, pregnant women face a risk of premature labor, bleeding, and other potentially devastating consequences.

People who have lived for centuries at high altitudes–in Tibet, the Ethiopian highlands, and the Andes–have genes that show signs of natural selection as an adaptation to high elevation. The Harvard researchers argue that pregnancy may have created a particularly strong pressure for such genes. A gene called BCL11A, for example, helps produce a special form of hemoglobin only found in fetuses. In Ethiopia, a variant of that gene has spread rapidly in the past few thousand years. Another potentially telling clue is the fact that Tibetan and Andean women don’t suffer many cases of low birth weight and other harm caused by high altitude. When women from nearby lowlands give birth at those high elevations, they have a higher risk of these problems.

At any elevation, pregnancy creates a quandary for a woman’s immune system.  Her fetus is not a perfect match to her own tissues, and so by all rights her immune system should attack it like a transplanted organ. A woman’s body avoids this devastating mistake with a number of strategies. For example, it suppresses its own immune system, so that it doesn’t unleash devastating inflammation.

While this may be good for the well-being of a woman’s baby, it’s dangerous to her own health because she’s left vulnerable to infection. In sub-Saharan Africa, for example, pregnant woman die two to three times more often from malaria than other people. During the flu pandemic of 1918, half of all infected pregnant women went on to develop pneumonia, which was 50% fatal. And in a sad irony, a disease acquired during pregnancy may lead to a spontaneous abortion or to low birth weight. In the spring of 1919, the birth rate dropped between 5 and 15% due to the deaths of pregnant women and their spontaneous abortions.

Sabeti and other scientists have identified a number of genes that show signs of having undergone strong natural selection for defenses against malaria and other diseases in the past few thousand years. One of those genes, called FLT1, turns out to be especially important for pregnant women. In Tanzania, where malaria is common, natural selection has favored a variant of FLT1 that lowers the rate of spontaneous abortion from the disease. Sabeti and her co-authors predict that more genes will show this special focus on pregnancy.

When evolutionary biologists seek to explain any pattern in nature, it’s always important to think about alternative explanations. And pregnancy is no exception. The high risk of gestational diabetes among South Asians in New York could conceivably not be the result of natural selection acting on a traditionally low-sugar diet. It could just be the shock of shifting from the diet of a poor country to an affluent one.

Fortunately, we don’t just have to juggle these alternative in a post-modern circus. Scientists can test them. They can pinpoint the genes that put women at risk of gestational diabetes (we don’t know them yet), and then look for signs that they’ve undergone natural selection in the past. Likewise, scientists can track immigrant families from different ethnic backgrounds over several generations to see if their risk of gestational diabetes drops or stays the same. This research may do more than reveal the fingerprints of evolution on our species. It may lead to better ideas for keeping babies and their mothers healthy during the troubled passage that is pregnancy.

Reference: Brown, Elizabeth A., Maryellen Ruvolo, and Pardis C. Sabeti. “Many ways to die, one way to arrive: how selection acts through pregnancy.” Trends in Genetics (2013)