Tiny stickleback fish helps researchers understand humans’ upright posture

Armor plating on a tiny fish may seem completely unrelated to the structure of a human foot, but researchers at Stanford University School of Medicine, in collaboration with scientists at the HudsonAlpha Institute for Biotechnology have found reason to connect the two.

As part of long-time professional affiliation – also a friendship – among colleagues at HudsonAlpha and Stanford, a team of scientists have identified a change in gene expression that could explain how humans evolved the ability to walk upright. The study was published Jan. 7 in Cell.

The project team, led by David Kingsley, PhD, of Stanford, used the genome for a tiny fish to study how genes are expressed in human legs and feet. The fish, called a threespine stickleback, has evolved different skeletal structures to adapt to a wide variety of environments around the world.

“We’ve worked with David on the stickleback genome for more than 10 years,” said Richard Rick Myers, PhD, science director and faculty investigator at HudsonAlpha. “David came up with the idea of developing the stickleback fish as a model research system to understand how small changes in genomes can lead to big changes in an organism. This has paid off in multiple ways, teaching us not only about the fish, but also about human evolution.”

For this study, the research team identified a gene – GDF6 – related to armor plating on the stickleback. They found that humans have lost the regulatory element that would control GDF6 expression. And in mice, losing that element is related to shorter toes. Since chimpanzees – our nearest living relative – have longer digits on their hind feet, the team concluded that changes in GDF6 regulation likely led to human’s upright posture.

Jeremy Schmutz and Jane Grimwood, PhD, both co-directors of the HudsonAlpha Genomic Sequencing Center, have also worked on the stickleback project.

“The stickleback provides an example of how a very simple genetic change in fish can result in a reduction in bone morphology,” said Schmutz. “And because it’s a regulatory change, it can have drastic consequences.”

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