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James Noonan: The How of Human Evolution

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Recommended by: Rick Myers, HudsonAlpha Institute for Biotechnology

Yale University's James Noonan would like to know what makes us human. Using functional genomics methods to study human evolution, and comparing early human development to that of classic models — particularly in limbs and in the cortex — he hopes to find the genetic changes that occurred in human evolution to make people different from other species. "The most prominent differences between humans and other species are developmental differences," Noonan says. "There are changes in brain size, changes in limb morphology, that allow us to walk upright, allow us to use tools, allow us to think. And these are grounded in developmental changes, changes in the way the limb is put together, changes in the way the brain is put together." To understand how those changes are encoded on the genetic level, one needs to understand their development in a comparative way, he adds.

Noonan says there are clinical applications to his work: Human limb malformation is fairly common, and there's evidence that developmental defects can be caused by mutations in regulatory sequences. "We don't even know where most of the regulatory elements are in the genome, not for any system, for any tissue, and we certainly don't know that for limb. So as a necessary step in our study, we're generating maps of regulatory functions in the limb itself, so that can feed into whole-genome sequencing projects where people are interested in looking for mutations in regulatory space," he says.

While he and his colleagues are good at the technical aspects of what they do, Noonan says there are still conceptual challenges. "When you tell people that you work in human evolution, studying the genetic basis of human uniqueness, people tend to think of that as a pie-in-the-sky idea, that it's not really possible," he says. "What we have to try to reinforce in our work, and when we describe our work and what we do, is that evolutionary differences among species are genetic, and there's no difference between studying a mutation that causes a particular phenotype in a species, and studying sequence differences across species and determining what they do."

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