Gene tweaking may have helped humans walk upright

Scientists have identified a change in gene expression between humans and primates that may have helped our feet to evolve into sturdy weight-bearing structures that allows us to walk upright.
Researchers studied a tiny fish called the threespine stickleback that has evolved radically different skeletal structures to match environments around the world.
"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 armour of the stickleback, but also in the hind-limb development of humans and primates," said David Kingsley, professor at Stanford University in US.

"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," said Kingsley.
The threespine stickleback has evolved to have many different body structures to equip it for life in different parts of the world.
The researchers found that a region that includes the gene for a bone morphogenetic protein family member called GDF6 was responsible for the skeletal differences that have evolved in natural populations.

In previous surveys, researchers 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. They homed in on one in particular.

"This regulatory information was shared through about 100 million years of evolution, and yet, surprisingly, this region is missing in humans," said Kingsley.
To learn more about what the GDF6 regulatory region might be controlling, the researchers used the chimp regulatory DNA to control the production of a protein that is easy to visualise in mice.
Laboratory mice with the chimp regulatory DNA coupled to the reporter protein strongly and specifically expressed the protein in their hind limbs, but not their forelimbs, and in their lateral toes, but not the big toes of the hind limbs.
Mice genetically engineered to lack the ability to produce GDF6 in any part of their bodies had skull bones that were smaller than normal and their toes were shorter than those of their peers.

These findings gave the researchers a clue that GDF6 might play a critical role in limb development and evolution.
The fact that humans are missing the hind-limb-regulatory region probably means that we express less of the gene in our legs and feet during development, but comparable amounts in our nascent arms, hands and skulls.
Loss of this particular regulatory sequence would also shorten lateral toes but not the first toe of feet.
This may help explain why the big toe is aligned with other short, lateral toes in humans. Such a modification would create a more sturdy foot with which to walk upright, researchers said.