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A recent Science Focus article discussed theories of why giraffes have long necks. The most obvious suggested that their length, which can reach up to 6 feet, evolved because it gives the animal access to the topmost leaves of trees, eliminating competition for food. Another theory is that the long neck is used as a weapon, wielded in fights between males. Male giraffes indulge in bouts of “neck fighting” to gain access to females, swinging their necks at each other and using their thick, heavy heads to break vertebrae. The males that reproduce most successfully do have the longest necks.

If sexual selection is the cause, males should have noticeably longer necks than females — but the difference is too small to be explained by sexual selection alone. Another theory is that the long neck helps the animal spot predators, or maybe the large surface area assists in regulating body temperature. It might also have evolved in response to giraffes’ legs getting longer, ensuring that they could continue to drink at waterholes.

Whatever the reason for the long neck, it creates a physiological engineering problem as described in a recent Science Advances article, which was summarized in a Science commentary. Researchers from China, Norway, and Denmark compared gene variants of a male giraffe with those of other mammals, including the giraffe’s closest relative: the short-necked, zebra-sized okapi. These animals diverged about 11.5 million years ago. The data identified 490 genes with unique adaptations in the giraffe. Many of the DNA variants were in genes linked to cardiovascular features, bone growth, and the sensory system.

A giraffe’s heart must pump blood at a pressure that is approximately 2.5 times higher than humans. DNA sequencing of the giraffe genome found seven unique DNA variants in the gene Fgrl1 (Fibroblast Growth Factor Receptor Like 1).

The researchers used CRISPR gene editing techniques to insert the giraffe variants into the Fgrl1 gene of mice. Not surprisingly, the mice did not grow long necks, and they did not show any obvious change in their cardiovascular system. However, when the researchers gave the modified mice a drug to induce high blood pressure, they stayed healthy, and their blood pressure rose only slightly. The unmodified control mice developed hypertension and associated kidney and heart damage.

The Fgfrl1 giraffe variant does something to the cardiovascular system that counteracts the effects of hypertension in mice, but the mechanisms are not known. There is not yet any evidence that Fgrl1 is one of the genes that causes hypertension in humans, but studying how the giraffe variants do protect mice from hypertension could lead to important new cardiovascular pathways for therapeutic investigations.

The study also highlights other DNA variants unique to the giraffe. Previous research has shown that giraffes have the best vision of all hoofed mammals, which — with their height — allows them to scan the horizon more effectively than other animals. The study also shows that the giraffe lost at least 53 olfactory genes compared with the okapi. So it traded its sense of smell, which is not as important given how far off the ground their head is, for improved eyesight — a definite benefit for their height. The team also found variants in genes that regulate sleep patterns. These findings could explain why giraffes only sleep 40 minutes per day and about three to five minutes at a time.

I use giraffes to illustrate the importance of genomic variants in health. We now know that DNA differences in the gene have profound physiological differences across all mammals. How is this example tied to UNC Research’s priorities? One of our seven research priorities is “Precision Health and Society,” which is focused on tailoring health care practice, delivery, and therapeutics to unique individual circumstances, using factors from genetics to social and environmental influences.

Francis Collins, director of the National Institutes of Health, has declared precision health a priority initiative for the agency as well.

“Precision medicine is really an effort to capture all of the specifics about an individual’s health from their environmental exposures, health behaviors, various aspects of their physiology, their metabolism, as well as genetic information through a variety of genomic loci,” Collins recently shared.

Just as giraffes’ necks allow them to reach great heights, the expertise of UNC researchers allows them to do the same across fields. I look forward to sharing more regarding Carolina’s unique contributions to precision health and society later this year.

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