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Biological Chemistry

A single amino acid can make a whale of a difference

Variations of an important metabolic protein may explain why baleen whales are so gigantic

by Emma Hiolski
July 31, 2017 | APPEARED IN VOLUME 95, ISSUE 31

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Credit: Mridula Srinivasan/NOAA (humpback); Chris Cutler (dolphin)
Baleen whales such as this humpback (bottom) have glutamine at position 156 in the melanocortin-4 receptor, whereas toothed whales and this spotted dolphin have arginine at that position.
Credit: Mridula Srinivasan/NOAA (humpback); Chris Cutler (dolphin)
Baleen whales such as this humpback (bottom) have glutamine at position 156 in the melanocortin-4 receptor, whereas toothed whales and this spotted dolphin have arginine at that position.

Dolphins and whales, marine mammals collectively known as cetaceans, range in size from 1 to 30 meters and feed on anything from fish and other marine mammals to krill and plankton. Scientists led by Roger D. Cone of the University of Michigan thought the melanocortin system, an important regulator of metabolism, food intake, and fat storage, might play a role in this breadth of cetacean size and feeding behavior. The researchers sequenced the melanocortin-4 receptor of 20 cetacean species and produced copies of the proteins through cell culture to study their properties. The two cetacean suborders turn out to have a single amino acid variation at position 156 in the melanocortin-4 receptor: glutamine for baleen whales and arginine for toothed whales and dolphins (Sci. Rep. 2017, DOI: 10.1038/s41598-017-05962-1). The arginine variant shows greater activity and higher affinity for binding its native ligand—a satiety signal that suppresses appetite—than the glutamine variant. This difference may help explain how filter-feeding baleen whales evolved to such gargantuan sizes. “We know that there are many genes that contribute to size,” Cone says. “But we found a mutation that fits with the hypothesis that this gene could be one of them.”

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