Genes reveal how our pelvis evolved for upright walking

The wide, basin-shaped human pelvis is a defining physical feature of our species. Without it, we couldn’t walk upright or give birth to big-brained babies. Now, a new study of human embryos has pinpointed the window in embryonic development during which the pelvis begins to look humanlike and identified hundreds of genes and regulatory RNA regions that drive this transformation. Many bear the hallmarks of strong natural selection for bipedalism, the authors conclude.

“It is a really impressive study, especially the genomic part, which uses all the bells and whistles of state-of-the-art-analysis,” says Marcia Ponce de León, an anthropologist at the University of Zürich (UZH) who was not involved with the work, which was reported this week in Science Advances. The results, she adds, support the idea that evolution often produces new physical features by acting on genetic switches that affect early embryonic development. Such predictions are “easy to state but very difficult to actually demonstrate, and this is what the authors did,” she says.

The pelvic girdle in primates consists of three major parts: blade-shaped bones, called ilia, that fan out to form the hips and, below those, two tube-shaped fused bones known as the pubis and ischium, which give shape to the birth canal. Great apes have relatively elongated ilia that lie flat against the back of the animals, as well as relatively narrow birth canals. Humans have shorter, rounded ilia that flare out and curve around. The reshaped ilia provide attachment points for the muscles that make upright walking more stable, and a wider birth canal accommodates our big-brained babies. Terence Capellini, an evolutionary biologist at Harvard University, says those pelvic patterns were already emerging in early human ancestors such as the 4.4-million-year-old hominin Ardipithecus ramidus, which had slightly turned-out ilia and is thought to have at least occasionally walked on two feet.

When and how those features take shape in human gestation had been mysterious, however. Many of the key human pelvic features, such as its curved, basinlike shape, are already developed by week 29. But Capellini wondered whether they might emerge earlier, when the pelvis has not yet turned to bone, but instead has scaffolding made from cartilage.

With the consent of women who had legally terminated their pregnancies, the researchers examined 4- to 12-week-old embryos under a microscope. They found that roughly around the 6- to 8-week mark, the ilium begins to form and then rotates into its telltale basinlike shape. Even as other cartilage within the embryo starts to ossify into bone, Capellini’s team found this cartilage stage in the pelvis seems to persist for several more weeks, giving the developing structure more time to curve and rotate. “These aren’t bones, this is cartilage that is growing and expanding and taking that shape,” Capellini says.

Next, the researchers extracted RNA from different regions of the embryos’ pelvises to see which genes were active at different developmental stages. Then, they identified hundreds of human genes within specific pelvic sections whose activity seemed turned up or down during the first trimester. Of these, 261 genes were in the ilium. Many of the downregulated genes are involved in turning cartilage to bone, whereas many of the upregulated genes maintain cartilage, Capellini says, and possibly act to keep the ilium in a cartilaginous stage for longer.

By comparing the developing pelvis’ genetic activity with a mouse model’s, the researchers also identified thousands of genetic on/off switches seemingly involved in shaping the human pelvis. Stretches of DNA within those switches appear to have evolved rapidly since our species’ split from our common ancestor with chimpanzees. But among modern humans, those regulatory bits in the ilium show strikingly little variation. That uniformity, the researchers say, is a sign that natural selection put—and continues to put—intense pressure on the ilium to develop in a highly specific way.

“We think this is really pointing to the origins of bipedalism in our genome,” Capellini says of his team’s work.

Martin Häusler, an anthropologist at UZH, says he’s not surprised at the evidence for intense selective pressure on the pelvis, but adds that the findings offer an impressive look into some of the pelvic changes “at the very origin of what makes us human.” Future work comparing human embryos with other primate embryos—rather than mouse models—would allow for an even better look at how natural selection reshaped the human pelvis, he adds.

The emerging understanding could also help scientists devise treatments for hip joint disorders or predict complications in childbirth, says Nicole Webb, a paleoanthropologist who studies pelvic anatomy at the University of Tübingen. Deviations from the genetic program that Capellini’s team identified can result in disorders such as hip dysplasia and hip osteoarthritis, she notes. “I hope that it has major implications for making people’s lives better. That would be huge, to connect paleoanthropology with real life,” Webb says.

source: sciencemag.org