Consider the American lobster—a bottom-dwelling crustacean that lives up to 100 years in the wild. Scientists have long wondered at its astonishing longevity: Lobsters do not grow weaker with age and only rarely suffer from cancers. Now, researchers have published the first high-quality draft of the lobster genome, yielding surprising insights about the animal’s immune system and genomic stability that may one day help answer fundamental questions about aging—not only in lobsters, but also in humans.
Lobsters are “very different from us,” says Jose Lopez, a molecular evolutionary biologist at Nova Southeastern University who was not involved with the study. “But we do share a lot of homologous genes with these seemingly very distant animals.” Lopez calls the new work “a monumental effort,” especially given that the lobster genome may be even longer than that of humans.
Much like a fine wine or certain Hollywood actors, American lobsters (Homarus americanus) seem to only get better with passing years. They do not lose strength, experience large shifts in metabolism, or lose fertility with age. They also spend their whole lives growing bigger and bigger. And whereas it is estimated that nearly 40% of all people will be diagnosed with cancer at some point, a 2008 literature review across more than 60 years of research found just one credible case of a tumorous growth in the American lobster.
To see whether lobster genes hold the secret to their cancer-free longevity, researchers at the Gloucester Marine Genomics Institute (GMGI) launched a project to sequence the animal’s entire genome in 2015. But by 2017, the team had sequenced less than half of the genome using standard “short-read” technology, which could only process very small fragments of the lobster genome at a time. Two GMGI researchers—biochemist Andrea Bodnar and marine biologist Jennifer Polinski—pushed for additional sequencing using newer long-read sequencing technology. But that meant they had to redo their entire analysis. “It was almost like starting over again,” Bodnar says.
By 2019, GMGI’s work had yielded the most complete lobster genome to date—capturing an estimated 72% of the entire sequence, the researchers report today in Science Advances. When Bodnar, Polinski, and colleagues in Florida, Maryland, Canada, and Russia analyzed the data—comparing their sequence with those of seven other marine invertebrates—they found dozens of examples in which groups of genes related to nerve cell function, immunity, genome integrity, and cell survival were enriched or expanded.
For example, the researchers found genes encoding a wide variety of proteins that help regulate the movement of ions through cell membranes, known as ligand-gated ion channels—and even discovered a new type of channel. Ion channels play key roles in many physiological processes, from nerve cells’ firing to immune cells’ recognizing foreign substances. The newly discovered ion channels combine functions typically found in the immune and nervous systems, suggesting unique neuroimmune interactions may contribute to the American lobster’s resistance to disease, Bodnar says.
The researchers were surprised to find that, compared with mammals and fruit flies, the lobster has few genes that activate programmed cell death. In most animals, that process inhibits tumors and gets rid of diseased cells. Because lobsters almost never get tumors, Polinski says, the team expected to find many more genes linked to activating programmed cell death. Instead, the researchers found many more genes known to inhibit it, suggesting lobsters may rely on other strategies to curb tumor growth.
Bodnar says more research could help explain how lobsters remain virtually cancer-free—and how those lessons might one day translate to people. “Humans already have a wonderfully long life span,” she says. “The problem with human biology is that we spend a lot of our life span in decline, and especially towards [our] older years, we get … increased incidence of disease and morbidity.” She hopes insights from the lobster genome might eventually lead to new medications or a new understanding of the role metabolism plays in longevity.
Meanwhile, Polinski sees a more immediate application for the lobster genome. “Lobsters are very sensitive to the temperature of the water,” she says. As waters in the North Atlantic Ocean have warmed, lobsters along the eastern U.S. and Canadian seaboard are moving north, decimating lobster fisheries across southern New England. Knowing more about how lobsters might react to such pressures, Polinski says, could help scientists better understand both how they will migrate in the years ahead and how their population structure may shift as it moves—and it might provide fishery managers with an important tool to predict their own futures.
sciencemag.org, 23 June 2021