Tweak in Gene Expression May Have Allowed Our Ancient Ancestors to Walk Upright

Your feet allow you to run and jump and walk. Now, scientists have found that the only reason we have feet that allow us to walk upright is due to a genetic tweak that occurred long ago.

"It's somewhat unusual to have a research project that spans from fish all the way to humans, but it's clear that tweaking the expression levels of molecules called bone morphogenetic proteins can result in significant changes not just in the skeletal armor of the stickleback, but also in the hind-limb development of humans and primates," said David Kingsley, one of the researchers, in a news release. "This change is likely part of the reason why we've evolved from having a grasping hind foot like a chimp to a weight-bearing structure that allows us to walk on two legs."

Although it may be counterintuitive, a fish told researchers about the genetic tweak. The threespine stickleback is remarkable since it has evolved to have many different body structures to equip it for life in different parts of the world. It has an exterior of bony plates and spines that act as armor to protect it from predators. In marine environments, the plates are large and thick; in freshwater, the fish have evolved to have smaller, lighter-weight plates, perhaps to enhance buoyancy and increase in flexibility. In this case, the researchers wanted to identify the regions of the fish's genome responsible for the skeletal differences that have evolved in natural populations.

The researchers identified the area of the genome responsible for controlling armor plate size, and then looked for differences there in 11 pairs of marine and freshwater fish with varying armor-plate sizes. They homed in on a region that includes the gene for a bone morphogenetic protein family member called GDF6. The fish the expressed higher levels of GDF6 developed smaller armor plates.

The researchers then looked at the differences in the genome of chimps and humans. In previous surveys, they found over 500 places in which humans have lost regulatory regions that are conserved from chimps and many other mammals. Two of these occur near the GDF6 gene.

"This regulatory information was shared through about 100 million years of evolution," said David Kingsley, one of the researchers, in a news release. "And yet, surprisingly, this region is missing in humans." He continued by saying, "These bone morphogenetic proteins are strong signals for bone and cartilage growth in all types of animals." In other words, this genetic anomaly, associated with hind-limb structures, was what did the trick.

The findings reveal a bit more about the evolution of animals. More specifically, it shows how humans may have evolved hind-limb structures that allowed them to eventually walk upright.

The findings are published in the journal Cell.

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