Psychology Today has described dopamine as the “reward molecule.”
Researchers have long pondered the evolutionary origins of this molecule linked to regulation of neural activity, gene expression, and social and reproductive behaviors.
“I personally think that the fact that receptors for dopamine were retained allowed vertebrates to develop complex personalities,” said Asher Baltzell, a doctoral candidate in the University of Arizona’s Genetics Graduate Interdisciplinary Program.
Baltzell, along with a team of UA scientists and Erich Jarvis of Howard Hughes Medical Institute, published a paper in the journal Frontiers in Neuroscience that illuminates the evolutionary origins of vertebrate dopamine receptors — the gateways to happiness.
Baltzell worked with Eric Lyons of the UA College of Agriculture and Life Sciences and BIO5 Institute and Fiona McCarthy with the UA’s Animal and Comparative Biomedical Sciences, along with iPlant Collaborative staff, in compiling the data for publication. His work was funded by the Arizona Biological/Biomedical Sciences Program.
By cross-comparing 50 recently sequenced avian genomes, along with genomes from a few other vertebrates, the researchers discovered that the current configuration of vertebrate dopamine receptors originated around 450 million years ago during phenomena known as whole genome duplication events. These uncommon genetic events occurred in the vertebrate common ancestor shortly after the genetic separation of vertebrates and invertebrates.
Baltzell sees two main applications of this study: agricultural and medical.
“Understanding how these receptors work and how you can possibly manipulate them are incredibly important in agriculture,” he said. “For example, brooding in chickens is behavior that you do not want if you want your chickens to keep laying eggs. There is a strong correlation between dopamine receptors and brooding. So if we understand how these work, it might be possible to mitigate or treat the behavior.
“For humans, there are a lot of implications for health,” Baltzell added. “It’s very difficult to resolve the exact functions of a receptor when there are multiple receptors that appear the same. By understanding the evolution, where they came from, how they duplicated, it can help guide research and uncover the differences in function.”
A Flock of Data
Until now, lack of sufficient vertebrate genomes or computational tools powerful enough to perform the necessary large-scale analyses prevented scientists from further investigating the origins of vertebrate dopamine receptors.
But Baltzell is a data scientist working with CoGe, a powerful comparative genomics platform developed by Lyons.
Storing genetic information of more than 24,000 genomes of nearly 17,000 organisms, CoGe derives its immense power from the computational framework of the iPlant Collaborative, the National Science Foundation’s premier data management and analysis platform led by the UA, of which Lyons is also a co-principal investigator.
“CoGe leverages iPlant’s cyberinfrastructure for user identity management and data scalability, allowing the CoGe team to focus on developing software for answering genome-driven questions,” Lyons said.
Additionally, Baltzell had access to 50 avian genomes, which recently had been sequenced by Jarvis and other researchers — sufficient data to investigate the evolutionary origins of individual genes.
“We were lucky that the evidence had been preserved in the bird genomes we investigated,” Baltzell said. “Placental mammals have lost two of the receptors since the duplication event, so you wouldn’t be able to see these events in human genomes, for example, because the genes have been deleted at this point. Whereas in birds, the code for the original receptors is still maintained in their genomes.”
Baltzell accessed the 50 bird genomes stored in iPlant’s Data Store, a cloud platform that allows researchers to securely store massive amounts of data.
“I started working on this project before publication of the bird genomes, so Jarvis was able to share the data with me securely through the Data Store before it had been made available to the public,” Baltzell said.
Meanwhile, CoGe allowed Baltzell to visualize and work with the genomes, running comparison analyses to locate the target genes for his study in each species’ genome.
Two by Two, the Molecules Came
“Two dopamine receptors in particular, DRD1A and DRD1B, were thought to have come from a whole genome duplication event, because they match certain patterns,” Baltzell said.
A whole genome duplication event is what happens when, during cellular replication — instead of splitting and copying a chromosome once, as usually happens — chromosomes are copied twice. “You wind up with two sets of every gene,” Baltzell said.
In plants, such double-chromosome operations are common. But in animals, it’s usually lethal, Baltzell explained, wreaking havoc on the regulatory functions of a fetus extremely early in development.
“There are rare occasions in which animal species have been known to survive whole genome duplication events,” Baltzell said. “There is a period called fractionation, where genes are rapidly lost to restore the genome to approximately its original size. However, not every gene is actually deleted. Some are retained, and now you have two copies of the same gene, which allows one copy to diversify and take on a new function while the first copy continues fulfilling its original purpose.
“We found that during two rounds of whole genome duplication early in the evolution of vertebrates, one of those events resulted in the duplication of two important dopamine receptors, DRD1A and DRD1B, and both duplicates were retained. It’s fairly unlikely that would happen.”
Why two dopamine receptors were duplicated — and more incredibly both retained in surviving vertebrate lineages — remains a genetic mystery, Baltzell said. “But it does seem to have implications on how vertebrates have developed since,” he said.
Dopamine receptors are chemically similar across all species, he explained, but how they’re expressed and the exact roles they play may vary, along with the number of receptors. For example, most bird species have all seven known dopamine receptors, while humans have only five.
Does this mean that birds are happier than humans?
“Potentially,” Baltzell said with a laugh. “There is quite a bit of interest in understanding the distinct roles of the different families of dopamine receptors.”
Source: University of Arizona