Beaches closed. Marine mammals sickened. Fisheries idled. These are some of the harms that may be caused by algae blooms if they turn toxic, that is, if algae start producing a potent neurotoxin called domoic acid. Although domoic acid’s structure has been known for decades, the domoic acid’s biosynthesis has been poorly understood. A new study, however, has uncovered the genetic basis of domoic acid production, encouraging researchers who hope to predict domoic acid events, or toxic tides, which threaten to become more frequent as climate change progresses.

The new study, informed by a knowledge of the growth conditions known to induce domoic acid production in the phytoplankton Pseudo-nitzschia, implemented transcriptome sequencing to sort through the genes thought likely to participate in domoic acid biosynthesis. Ultimately, the study identified a cluster of genes that are “switched on” when the phytoplankton produces domoic acid.

Details appeared in the journal Science, in an article titled, “Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom.”

“[We identified domoic acid (DA)] biosynthesis genes that colocalize in a genomic four-gene cluster,” the article’s authors wrote. “We biochemically investigated the recombinant DA biosynthetic enzymes and linked their mechanisms to the construction of DA’s diagnostic pyrrolidine skeleton, establishing a model for DA biosynthesis.”

By showing how genes for domoic acid production are turned on, the authors suggest a way to connect the ocean conditions that drive algae blooms with the development of toxin production.

Harmful algae blooms often come in the form of “red tides,” so called because of the reddish tint they lend ocean waters. The blooms occur when phytoplankton grow rapidly, sometimes producing toxins that can sicken marine mammals and other species.

Harmful algae blooms also pose a threat to human health when the toxins accumulate in seafood. A high-dose exposure to domoic acid can lead to amnesic shellfish poisoning, a potentially fatal condition marked by seizures and short-term memory loss.

“By identifying the genes that encode domoic acid production, we are now able to ask questions about what ocean conditions turn these genes on or off,” says Patrick Brunson, lead author of the study. Brunson is affiliated with the Scripps Institution of Oceanography (SIO) and the J. Craig Venter Institute. “The knowledge will allow us to track the development of bloom toxicity at the genetic level.”

The current study was based on earlier observations that the phytoplankton’s toxicity increases under phosphate limitation and elevated CO2 concentration. “A comparison revealed that the transcription of ∼500 genes increases under phosphate starvation,” noted a Science Perspective that accompanied the main paper. “Transcription of only 43 of these genes also increased under high-CO2 conditions; the authors used these transcripts to look for domoic acid biosynthetic genes.

“The oxidase with the most pronounced increase in transcription was located in a genomic region where additional genes showed up-regulated expression. This clustering facilitated the breakthrough because it turned out that all these genes were involved in domoic acid biosynthesis.”

Several states have been severely impacted by harmful algae blooms. The largest harmful algae bloom ever recorded happened in the summer of 2015 off the West Coast of North America from Alaska to California, and resulted in the closure of fisheries to protect consumers from potential shellfish poisoning.

Harmful algae blooms are difficult to forecast, scientists have found. The bloom-causing organisms usually have very complex genomes. Knowledge of the genes involved in domoic acid production will allow for better monitoring of algae blooms, scientists say, and aid in identifying the conditions that trigger toxin production.

“Because the genomes of the algae are so complex, the biosynthetic pathways for marine microalgae toxins have remained elusive for some time,” said the main article’s senior author Bradley Moore, Ph.D., a chemist and geneticist at SIO and the University of California, San Diego's Skaggs School of Pharmacy and Pharmaceutical Sciences.

“Now that we have a genome for Pseudo-nitzschia and a genetic pathway for domoic acid production, we're beginning to understand why these microalgae make a toxin and how that capability is activated,” Dr. Moore says. “This new knowledge will better educate us on how to predict and prepare for future toxic events.”

When phosphate in the ocean is limited and the amount of carbon dioxide increases, Pseudo-nitzschia can make large amounts of domoic acid and become harmful.

Carbon dioxide in the sea is increasing above natural levels. Along with rising ocean temperatures, these conditions lead to more prevalent, more toxic, and longer-lasting blooms and domoic acid production.

Researchers who work on monitoring and forecasting harmful algae blooms say the findings offer an increased understanding of the phenomenon, and will help predict domoic acid events in response to climate change.