Pygmy populations, scientists have speculated, may owe their abbreviated stature to natural selection pressures that allowed them to better adapt to dense tropical forests where heat is oppressive and food is scarce. “An outstanding question for many, many years among anthropologists and human geneticists has been what is the genetic basis of the short stature trait in Pygmy populations globally and in Africa in particular, says Sarah Tishkoff, a professor at the University of Pennsylvania, who is a leading expert on African population genetics. “There’s a good reason to think it’s adaptive because in fact in regions of dense tropical forests globally you often have these short-statured Pygmy groups.”

Tishkoff and colleagues have found an unexpected surprise in genetic evidence for Pygmy height, which reaches an average of 4 feet 11 inches in Pygmy men in Cameroon. They report in PLOS Genetics today on a set of genes that regulate immune and hormonal processes, and which only secondarily may be linked to height. Pygmies receive an intense assault from pathogens that flourish in the forest and that turn up routinely in their bush-meat diet: expected lifespan is less than 18 years. It may be that genes that protect against microbes may also hinder growth. Diminished stature could be a byproduct of bolstering immune and metabolic defenses and not a direct adaptation to a hunter-gatherer lifestyle.

The study was the most incisive to date looking at the genetics of height in Pygmies. Over many generations, pygmies have interbred with neighboring Bantu populations. The researchers scanned the genomes of 67 Pygmies and 58 Bantus for genetic markers, called single nucleotide polymorphisms, throughout the genome. They found that more Bantu ancestry translated into a taller individual, a confirmation that genes were involved with height differences. They then looked more closely at the genomes of the two groups. A section of chromosome 3 differed greatly in Pygmies, a segment that also turned out through further analysis to show signs of being subject to selective pressures and to be correlated with height.

In the area that stood out, a genetic variant in CISH, a gene known to regulate immune responses and linked to resistance to bacteremia, malaria and tuberculosis, attracted notice. CISH also happens to inhibit production of human growth hormone. Mice genetically engineered to produce high levels of the CISH protein are undersized.

The research was designed to account for the exigencies of studying a small difficult-to-access population group. "For a typical complex trait like height in Europeans, you need a very large sample size which was not not feasible to collect for remote hunter-gatherer population," Tishkoff says. "However, our approach that looks at sections of the genome that are targets of natural selection and then looks at associations of those regions with height gives us more statistical power in identifying regions of the genome that play a role in the short stature trait in Pygmies."

Tishkoff says that other studies will undoubtedly turn up genes tied to height in Pygmies and natural selection may still be found to play a direct role in giving rise to short stature. Tishkoff worked closely with Joseph Jarvis, now at Coriell Institute for Medical Research, and Alain Froment of the Musée de l'Homme in Paris, who collected the Pygmy genetic samples.

Another gene that turned up on chromosome 3, DOCK3, has been associated with height in studies of European populations. But none of the hundreds of other height-related genes found in other groups were present in the Pygmy genetic analyses. ”It’s possible that Pygmies, due to strong selection pressures and their unique demographic history, may have a different genetic architecture of height,” Tishkoff says.

Africa has the most genetic diversity of any global region, the reason for Tishkoff’s research concentration. The study of height there illustrates how that diversity translates into differences in physical traits. Africa is also home to the tall, thin Dinka people in the upper Nile who tower about over Pygmies.


Source: Sarah Tishkoff