Monday, April 27, 2015

Why hummingbirds taste sweets but chickens can't

Chicken tastes good but, like most birds,
 chickens can't taste sweets1.
What about hummingbirds who live on nectar?

Hummingbirds can taste sugars because natural selection refashioned an savory receptor inherited from ancient fish into a unique sugar receptor. The elegant research was published in 2014 2.

In mammals, fish, amphibians, and reptiles, taste buds (shown to the left) distinguish five taste modalities - sour, bitter, salty, savory (also called umami) and sweet. The sweet and umami receptor proteins are "dimers", pairs of proteins that wind back and forth across the cell membranes of taste cells like the green taste receptor proteins shown in the cell membrane to the right. Sweet receptors, inherited from a fish ancestor, are paired T1R1 and T1R2 proteins while umami receptors are T1R1-T1R3 dimers.
Thanks to Maude Baldwin, a graduate student at Harvard University, we have recently learned a great deal about the story behind hummingbird sugar receptors2.

At the start of her work, Maude Baldwin knew that:
   = Hummingbirds feed on nectar so can't be sugar-blind.
   = T1R1 and T1R3 genes are present in chickens3.
   = The T1R2 gene in the ancestral sugar receptor is
      completely missing from a chicken's DNA3.

As fish evolved into ancient reptiles and reptiles gave rise to birds, when was the gene lost? When Maude looked at the DNA of several different species of birds, she found T1R1 and T1R3 but no T1R2. She examined alligator (primitive reptile) DNA and found all three genes. From this result, she surmised that some early ancestors of birds, probably dinosaurs, must have lost the T1R2 gene2

Next, Maude Baldwin made a very clever guess:
  • Maybe natural selection, operating over many millions of years, repurposed the hummingbird T1R1-T1R3 receptor by transforming hummingbird T1R3 into a sweetie detector? 
As she searched for ways to test that hypothesis, Maude talked with Stephen Liberles, a Harvard medical school faculty member specializing in the cell biology of chemoreception. Liberales connected Maude with Yasuka Toda, another graduate student halfway around the globe at the University of Tokyo.

Yasuka Toda and her colleagues had invented a sophisticated technique to study human T1R1, T1R2, and T1R3 function by inserting the corresponding genes into engineered laboratory-cultured human kidney cells (HEK293T).  Whenever sugars bind to T1R1-T1R2 or whenever savories bind T1R1-T1R3, the HEK293T cell emits a flash of light.  The cell is a reporter that announces sugar binding with its bioluminescece.

In response to a request from Maude Baldwin, the Tokoyo group inserted hummingbird T1R1 and T1R3 genes into their reporter HEK293T cells and applied either sugary or savory stimuli.  The modified cells with only one hummingbird gene (T1R1 or T1R3) showed no response. However, cells with both hummingbird T1R1 and hummingbird T1R3 flashed brightly when exposed to sugar.

Maude Baldwin's schrewd guess was proved correct! The ancestral dimer for savories (T1R1-T1R3) has become adapted for sugars in hummingbirds.

Not content with this beautifully clear result, the team went further and asked exactly which parts of the modified T1R3 protein were most critical.

Proteins are long loopy chains of amino acids. The Tokyo group constructed protein "chimeras". Chimera means a multi-species hybrid. The word traces back to a mythical Greek monster-lion with the head of a goat on its back and a snake in place of the tail.  The hummingbird team concentrated on the Venus Flytrap Domain of the hummingbird T1R3 gene (binds sugars) into which they stitched sequences of the chicken T1R3 gene (binds savories).

The chimeric T1R3's allowed the researchers to map exactly which amino acids are necessary to bind sugars, as shown in color on the T1R3 model to the right.

Next, the scientists exposed hummingbird T1R1-T1R3's in HEK293T cells to a broad panel of tastants (sucrose, various sugars, artificial sweetners like aspartame, and others). By making an inventory of tastants that triggered light flashes, they defined the taste spectrum for this human cultured cell with hummingbird T1R1-T1R3 receptors.

Do the impressive laboratory results fit with the natural world?  Does the taste spectrum, deduced from precisely controlled laboratory experiments with cultured human cells, really mesh with the way that hummingbirds taste different sugars?

To find out the answer,  Baldwin tested Ruby-throated Hummingbirds in her Harvard laboratory and another collaborator, Klaus Klasing, tested Anna's hummingbirds in the Santa Monica Mountains of California with a panel of tastants. The birds briefly tasted pure water (upper) but drank long at the sugar solution (lower) in the video from Baldwin's lab.

The real-world choices of intact birds in Massachusetts and California agreed well with the taste spectrum predicted by the HEK293T cell chimeras.  Hummingbirds have evolved the taste talent that matches their feeding ecology because natural selection retuned the ancestral savory sensor into a sugar sensor.
This astounding tour de force demonstrates the best practices of 21st century science - reaching across disciplinary boundaries to ask about animal adaptations and their evolution.

In closing, we should identify the roles of the members of the team:
  • Maude Baldwin, graduate student at Harvard who spearheaded the research,
  • Scott Edwards, Professor of Organismic and Evolutionary Biology and Curator of Ornithology in the Museum of Comparative Zoology and Baldwin's  faculty sponsor at Harvard,
  • Yasuka Toda (graduate student) and colleagues Associate Professor Takumi Misaka and Tomoya Nakagita in the Department of Applied Biology at the University of Tokyo who developed the cellular assay system for tastant proteins, 
  • Mary J. O'Connell in Dublin, Ireland who provided computational and bioinformatics expertise, 
  • Kirk Klasing at UC Davis who did field tests on Anna's hummingbirds, and 
  • Stephen D. Liberles, a cell biologist at Harvard's medical school who specializes in the molecular cell biology of chemoreception, including responses to pheromones.
For much of the 20th century, the chemical ecology of birds was neglected, but bird taste and olfaction are fast becoming hot topics.

Baldwin's lovely study of hummingbird sweet taste is particularly solid because it sweeps from natural behavior in the field to sophisticated molecular and cell biology in the lab and ties the story together with evolution, the unifying intellectual theme of all biology.

There are many related research questions. No ancestral sugar receptor gene has been found in any bird yet many species, for example house finches, are attracted to colorless sugary solutions.

It is heartening to learn from her webpage that Maude Baldwin is now applying her impressive intellect to bird pheromones.  In the next few decades, I expect myriad exciting new insights about avian chemical communication channels and their biological significance. See for example our speculation about the role of pheromones in Sandhill Crane reproduction.

References & Notes

1. BP Halpern 1982. Gustatory nerve responses in chickens. Am J Physiology 203:541-4

2. MW Baldwin, Y Toda, T Nakagita, MJ O'Connell, KC Klasing, T Misaka, SV Edwards, and SD Liberles, 2014. Evolution of sweet taste perception in hummingbirds by transformation of the ancestral umami receptor. Science 345:929-933.

3. P Shi, J Zhang, 2006. Contrasting modes of evolution between vertebrate sweet/umami receptor genes and bitter receptor genes. Mol Biol Evol 23:292-300.

4. Taste modalities are repeatedly lost in evolution. Penguins, like all birds, lack the ancestral sugar receptor. In  addition, penguins have lost the functional genes for both umami and bitter taste receptors. See  H Zhao, J  Li,  J Zhang, 2015. Molecular evidence for the loss of three basic tastes in penguin. Current Biology 25:R141-R142.

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