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Like the red blood cells of people with sickle cell anemia, the red blood cells of the muntjac, a type of deer from Asia, can distort into abnormal shapes.

P. D. Butcher

170-year-old mystery solved: Why deer have deformed blood cells just like some people

Deer and sickle cell anemia sufferers have something in common: Their red blood cells contort into abnormal shapes. Now, researchers have pinpointed the molecular change in deer’s blood cells that causes this distortion. The discovery solves a mystery that has puzzled researchers since the 1840s, and it may help scientists nail down how misshapen blood cells defend some people from malaria.

Working out the molecular basis for sickling in deer is “a great step,” says pediatric hematologist Vijay Sankaran of Harvard Medical School in Boston, who isn’t connected to the research.

People with sickle cell anemia carry a mutation that tweaks the structure of hemoglobin, the molecule that ferries oxygen through our blood. This DNA glitch makes β-globin—one of the two types of proteins that make up hemoglobin—stickier, causing the hemoglobin molecules to adhere and form stiff fibers. In turn, the fibers warp the normally disklike red blood cells into crescents or other abnormal shapes. People with the condition can suffer from pain, fatigue, and organ damage as their distorted, fragile red blood cells jam small blood vessels or burst.

Blood cells from several species of deer also sickle, but scientists don’t know what prompts the change. So molecular evolutionary biologist Tobias Warnecke of the Medical Research Council’s London Institute of Medical Sciences and colleagues gathered blood, muscle, and DNA samples from 15 deer species from around the world. Most of the specimens came from zoo animals, but to obtain tissue from two types of deer, moose, and reindeer, Warnecke says they had to order steaks from a company that sells rare meats.

Those two species, along with North American elk, don’t show red blood cell sickling. When the scientists compared the amino acid sequences of their β-globin proteins with the sequences from deer whose cells do sickle, they found one key difference: In the sicklers, one amino acid had switched from glutamic acid to valine. The same amino acid swap happens in the faulty form of hemoglobin that triggers sickle cell anemia, but at a different location in the molecule.

The switch in deer appears to make their hemoglobin molecules prone to cluster into fibers, the team reports online today in Nature Ecology and Evolution. But unlike humans, deer with sickled cells seem totally healthy. “I’m sure there’s a cost, but I have no idea what it is,” Warnecke says.

For humans, the cost of sickling is clear. In the United States, people with the disease typically don’t live past 50. However, the faulty β-globin gene remains unexpectedly common in parts of the world where malaria is prevalent. That’s because people with just one defective copy of this version of the gene gain some protection from malaria, although researchers aren’t sure how the altered protein counters the parasite that causes the disease.

Sickling must also confer some sort of advantage to deer, Warnecke and colleagues conclude; an evolutionary analysis the team carried out suggests that the animals have been making normal and pro-sickling versions of β-globin for more than 10 million years.

Next, the researchers will test different populations of white-tailed deer to determine whether the abundance of malaria parasites tracks with the prevalence the β-globin version that promotes sickling. If mutated β-globin is helping the deer resist malaria, figuring out how might help scientists better understand how deformed red blood cells help humans rebuff the parasites, Warnecke says.

Still, there’s a big difference between sickling in humans and deer, says hematologist Martin Steinberg of Boston University School of Medicine. In people, cells change shape when oxygen levels are low, but in deer they sickle when oxygen is abundant. Nevertheless, he says, the researchers revealed “considerable detail about the mechanism of sickling” in deer. Moreover, he adds, the work deepens a mystery about the animals. “I want to know why this sickling doesn’t make the deer sick.”