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How parrot feathers might speed up basic chemistry and medical research

If you have ever wondered why some parrots are green and others are blue, science now has an answer for you – and, the researchers behind the results say, the techniques they developed in the process could one day lead to the discovery of new chemical compounds or biomolecular processes that could impact human health.

It began over dinner, with a discussion of chocolate – specifically, the domestication of chocolate’s main ingredient, cacao. Thomas Cooke, PhD, then a graduate student in genetics, had been working on tools to study “non-model organisms,” plants and animals that get less attention than, say, lab rats, fruit flies, or baker’s yeast – the go-tos for much of chemistry, biology, and medicine – despite the potential for yielding important scientific insights. Cooke had been working on cacao, but the project had, he said, “fizzled,” and he was looking for what to do next.

Mulling that over at their favorite Palo Alto diner, biochemistry graduate student Kathleen Xie mentioned to Cooke a peculiar trait of the budgerigar parrots (Melopsittacus undulatas) she’d raised growing up: wild budgies are green and yellow, but others have been bred since the 19th century to be blue and white – and no one knew exactly how, on a genetic or molecular level, that happened.

Cooke, Xie and colleagues set out to figure out what was in some ways the perfect test case for the methods Cooke had been working on. It had been known for years that wild budgies’ color came from a yellow pigment the budgies themselves produce, and it had been known even longer that their color was a Mendelian trait, that is, budgies either made the yellow pigment or they didn’t. It should therefore be straightforward, if not exactly easy, to track down the gene responsible for determining budgie color.

Working with Stanford ChEM-H’s one-year-old Metabolic Chemistry Analysis Center and researchers from around the chemical and life sciences – and members of the American Budgerigar Society and the Budgerigar Association of America, who provided samples and advice – Cooke tracked blue budgies’ color to a gene responsible for regulating a chemical they dubbed MuPKS, for Melopsittacus undulatas polyketide synthase. A change to just one amino acid that makes up MuPKS, the researchers found, stops budgies from producing yellow pigment, revealing an underlying blue color in the birds’ feathers. To confirm those results, the team next transferred MuPKS gene into baker’s yeast and showed that the yellow variant turned yeast yellow, while the other variant had no effect on color.

Even if parrot color itself doesn’t turn out to be the most interesting subject scientifically, the study is harbinger of things to come, said Carlos Bustamante, PhD, a professor of biomedical data science and of genetics and one of the paper’s senior authors. “What Thomas conceptually demonstrated was we could go into any organism” and learn something interesting and useful about its biochemistry, Bustamante said.

In the future, the techniques Cooke developed – and the ever-declining cost of genetics research in general – could help scientists as a group look at many different plants and animals at once, increasing the likelihood someone will find the next key medicinal compound or biochemical pathway sooner rather than later. “It really demonstrates the power of emerging model systems,” Bustamante said.

“To me, the highlight of the story is Tom Cooke,” said Chaitan Khosla, PhD, a professor of chemistry and chemical engineering and director of ChEM-H. Cooke and his work, Khosla said, exemplify a new approach to life sciences that bridges work in genetics, biochemistry, and other fields.

Photo by James De Mers

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