Evolution, genetics, single-cell genomics, biochemistry… this story of parrot pigments has it all.
November 11, 2024
One of the significant findings of the past few decades in genomics is that animal species, despite their vast differences in morphology, physiology, and behavior, share more or less the same repertoire of genes. What truly distinguishes humans from chimps, mice, or whales is how this largely common set of genes is regulated. In other words, evolution often innovates not by inventing new genetic parts, but by tuning the activity of those parts in different tissues.
This idea is widely accepted in biology, and the implication is that to understand evolution at a molecular level, we need to learn how genetic changes in regulatory DNA elements lead to changes in cell physiology, which in turn affect organismal traits and fitness. While evidence of natural selection acting on particular regulatory DNA elements is fairly accessible, uncovering the mechanistic details linking sequence variants to organismal traits remains challenging. Clear examples of this process are relatively rare.
We were fortunate to contribute to a recent paper describing a new example of regulatory evolution, a project led by our WashU colleague Joe Corbo and his long-time collaborators at the University of Porto, Miguel Carneiro and Pedro Miguel Araújo. Published in the Nov. 1 issue of Science, the paper reveals a remarkably simple regulatory mechanism controlling the bright colors of parrot feathers.
The dusky lory is a parrot native to New Guinea, with red and yellow forms that coexist in natural populations. Credit: Pedro Miguel Araújo.
We first heard about this story in late 2022, when Joe shared that his team had mapped a non-coding, single-nucleotide genetic variant responsible for the red and yellow morphs of the dusky lory. They suspected this variant controlled the expression of a factor influencing the pigments responsible for these color morphs. The variant lies in a regulatory DNA element active in the correct cell type—keratinocytes of regenerating feather follicles—determined through single-nucleus ATAC-seq in budgerigars, a more manageable parrot species. This element is near the gene ALDH3A2, which encodes an aldehyde dehydrogenase, a ubiquitous enzyme not previously linked to feather pigment synthesis.
Joe’s team suspected that ALDH3A2 might regulate feather color. Aldehyde dehydrogenase enzymes like ALDH3A2 convert aldehydes to carboxylic acids. Red and yellow parrot feather pigments, known as psittacofulvins, exist in two chemical forms: a yellow carboxylic acid and a red aldehyde. Working with Jindřich Brejcha, a chemist at Charles University, the research team hypothesized that ALDH3A2 levels might tune feather pigments, with higher expression favoring yellow feathers and lower expression favoring red.
We had the opportunity to join the project by leveraging yeast, an area of expertise in our lab. In a 2017 study, Stanford biochemist Carlos Bustamante demonstrated that introducing a polyketide synthase enzyme into yeast could produce yellow psittacofulvins. Since yeast have a homolog of ALDH3A2, we predicted that disrupting the yeast homolog would shift the pigments from yellow to red, mirroring the role of ALDH3A2 in parrots.
This is exactly what happened. In summer 2023, lead author Roberto Arbore, a brilliant scientist in Miguel Carneiro’s group, worked in our St. Louis lab to engineer yeast. He showed that deleting the yeast version of ALDH3A2 resulted in red pigments, while reintroducing the dusky lory version restored yellow pigments.
There’s much more to the story, and we encourage you to read the full paper or listen to Joe and Roberto discuss it on NPR. A standout theme is the phenotypic diversity achieved by cell type-specific regulation of a ubiquitous enzyme. ALDH3A2, conserved across eukaryotes, has roles ranging from sphingolipid metabolism in humans to pigment synthesis in parrots. Over 50-80 million years of parrot evolution, this enzyme’s regulation has generated stunning color variations using the same basic genetic toolkit—a testament to evolution’s creativity in reusing common parts in new ways.
The team @ mgi
