Accidental shortness

Scientists who study human evolution have long puzzled over why African Pygmies are so short.

It is one of the most visible examples of human diversity, with Pygmy males standing just 4-foot-11 on average, while some of their neighboring ethnic groups are tall. Many biologists have assumed there must be some direct evolutionary advantage to their short stature — perhaps that they better maneuvered through the forest or they survived on less food.

A University of Pennsylvania team went looking for an answer in the Pygmies' DNA. "This is a trait that has fascinated anthropologists and human geneticists, but it's only today that we have genetic tools to address it," said Penn geneticist Sarah Tishkoff.

In a paper published last week, she, Coriell Institute researcher Joseph Jarvis, and colleagues reported that they found many differences between Pygmy DNA and that from neighboring Bantus, but none that would alone account for the Pygmies' stature, or tie it to an evolutionary benefit, if such a benefit ever existed.

Tishkoff was left wondering if genetic variants that led to shortness spread in the Pygmy populations because they got stuck to mutations that had other benefits. Pygmy shortness may be part evolutionary by-product, part accident. The findings back the views of some biologists who say their colleagues have too readily assumed there are survival advantages behind everything evolution produces.

About 40,000 Pygmies live in Africa, mostly in Cameroon, said Alain Froment, an anthropologist and medical doctor from the Musee de l'Homme in Paris, who collaborated on the study, published last week in the journal PLoS Genetics.

Pygmies lived as hunter-gatherers for centuries, Froment said. Today many still like to hunt and prize wild plants, caterpillars, and honey, he said, but they also eat cultivated foods — bananas and cassava — and use cellphones and other modern conveniences. For the genetic study, he took blood from 67 volunteers living in Pygmy villages, and carefully measured their height. He offered them free medical and dental care in return, as well as a screening for the sickle cell anemia mutation.

As a distinct group, Pygmies are ancient, having branched off from other Africans between 60,000 and 70,000 years ago. At that time, modern humans had yet to leave Africa, Neanderthals and other archaic humans populated Europe and Asia, and America was yet to be populated by any form of humanity.

Tishkoff has been a leader in collecting DNA from Africans because she realized they are underrepresented in genetic studies even though their DNA holds a big part of the story of all humanity. Our species had been spreading and diversifying through Africa for tens of thousands of years before populating the rest of the world. Native Europeans, Australians, American Indians, and others represent small subsets of a diverse population that started in Africa.

"If we want to understand global human diversity, we need to study Africa," said University of Washington geneticist Josh Akey, who was not part of Tishkoff and Jarvis' study. "And stature is one of those quintessential human traits we've been interested in."

For eons, the Pygmies were isolated, but over the last 4,000 years they have periodically mixed a little with their farming neighbors, the Bantu, Tishkoff said. The genetic analysis was able to identify certain markers associated with Bantu heritage, she said, and they found that the tallest Pygmies had the most Bantu ancestry. That connection was evidence that Pygmy shortness is an inherited trait, not one caused by an unusual diet or some other environmental factor.

Tishkoff and Jarvis found dozens of swaths of genetic code that were more prevalent in Pygmies, and some of those were correlated with height. Embedded in those swaths of DNA were genes known to influence a variety of biological substances including thyroid hormone, insulin, and growth hormone.

Tishkoff said one of the more interesting genes that might be connected to Pygmy height is called CISH. Among other things, it's connected to immune proteins called cytokines, which can help fight off infections. Those cytokines also affect the body's ability to react to human growth hormone. "There's a lot of cross-talk between the immune system and the neuroendocrine system," she said, the latter term referring to the system of hormones that govern behavior and growth.

It makes sense that natural selection would favor strong immune systems in Pygmies.

Unlike the Bantu, Pygmies live in tropical forests, which have a high diversity of life, including disease agents and parasites. Infectious disease is a major killer of Pygmies, Tishkoff said. Their life expectancy at birth is about 23. While there are elders in their 60s and 70s, the average is pulled down by a high rate of child mortality.

Tishkoff said it's possible that there's no advantage at all to being short, but that the Pygmies' shortness was a side effect of some beneficial mutation that helped them better fight parasites and diseases.

The study also deployed techniques that can pinpoint where the Pygmies' DNA has changed most recently. Akey helped pioneer those techniques. He said a mutation that is spreading rapidly tends to carry a large amount of other DNA along with it. Recent evolutionary change imparts a "signature pattern" on the DNA, he said, and such patterns showed up in the Pygmies in this study.

There were all kinds of genes that were recently altered — ones that govern not only hormones and immune function but also brain chemicals such as serotonin and oxytocin. Tishkoff explains that these substances can multitask and may have switched jobs over evolutionary history. And they tend to influence one another, acting more as orchestra members than soloists.

It would have been surprising if the researchers had found a simple answer, said Ken Weiss, a geneticist at Pennsylvania State University. "Not only is everything not necessary due to natural selection, but traits are distributed over many genes and most genes contribute to multiple traits," he said. "We don't like complexity because science isn't designed to deal with it," he said. But that's the way evolution made us.

Contact Faye Flam at 215-854-4977 or fflam@phillynews.com, or follow on Twitter @fayeflam. Read her blog at philly.com/evolution.