Around 400 million years ago, the ancestor of all four-limbed creatures took its first steps onto dry land. Fast-forward about 350 million years, and a descendant of these early landlubbers did an about-face: It waded back into the water. With time, the back-to-the sea creatures would give rise to animals vastly different from their land-trotting kin: They became the magnificent whales, dolphins, and porpoises that glide through the oceans today.

Going back to being aquatic was a drastic move that would change the animals inside and out, in the space of about 10 million years—an eyeblink in evolutionary terms. Members of this group, now called cetaceans, dropped their hind limbs for powerful flukes and lost nearly all their hair. For decades, their bizarre body plans perplexed paleontologists, who speculated they might have arisen from creatures as varied as marine reptiles, seals, marsupials like kangaroos, and even a now-extinct group of wolf-like carnivores.

“The cetaceans are on the whole the most peculiar and aberrant of mammals,” one scientist wrote in 1945.

Then, in the late 1990s, genetic data confirmed that whales were part of the same evolutionary line that spawned cows, pigs, and camels—a branch called Artiodactyla. Fossils from modern-day India and Pakistan later fleshed out that family tree, identifying the closest ancient relatives of cetaceans as small, wading deer-like creatures.

But their body plans are just the start of cetaceans’ weirdness. To survive in the sea, they also had to make internal modifications, altering their blood, saliva, lungs, and skin. Many of those changes aren’t obvious in fossils, and cetaceans aren’t easily studied in the lab. Instead it was, once again, genetics that brought them to light.

With an increasing availability of cetacean genomes, geneticists can now look for the molecular changes that accompanied the back-to-water transition. While it’s impossible to be certain about the influence of any particular mutation, scientists suspect that many of the ones they see correspond to adaptations that allow cetaceans to dive and thrive in the deep blue sea.

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Diving into the depths

The first cetaceans lost a lot more than legs when they went back to the water: Entire genes became nonfunctional. In the vast of book of genetic letters that make up a genome, these defunct genes are among the easiest changes to detect. They stand out like a garbled or fragmented sentence, and no longer encode a full protein.

Such a loss could happen in two ways. Perhaps having a particular gene was somehow detrimental for cetaceans, so animals that lost it gained a survival edge. Or it could be a “use it or lose it” situation, says genomicist Michael Hiller of the Senckenberg Research Institute in Frankfurt, Germany. If the gene had no purpose in the water, it would randomly accumulate mutations and the animals would be no worse off when it didn’t function anymore.

Hiller and colleagues dove into the back-to-water transition by comparing the genomes of four cetaceans—dolphin, orca, sperm whale and minke whale—with those of 55 terrestrial mammals plus a manatee, a walrus, and the Weddell seal. Some 85 genes became nonfunctional when cetaceans’ ancestors adapted to the sea, the team reported in Science Advances in 2019. In many cases, Hiller says, they could guess why those genes became defunct.

For example, cetaceans no longer possess a particular gene—SLC4A9—involved in making saliva. That makes sense: What good is spit when your mouth is already full of water?

Cetaceans also lost four genes involved in the synthesis of and response to melatonin, a hormone that regulates sleep. The ancestors of whales probably discovered pretty quickly that they couldn’t surface to breathe if they shut off their brains for hours at a time. Modern cetaceans sleep one brain hemisphere at a time, with the other hemisphere staying alert. “If you don’t have the regular sleep as we know it anymore, then you probably do not need melatonin,” says Hiller.

The long periods of time that whales must hold their breath to dive and hunt also seem to have spurred genetic changes. Diving deep, as scuba divers know, means little bubbles of nitrogen can form in the blood and seed clots — something that was probably detrimental to early cetaceans. As it happens, two genes (F12 and KLKB1) that normally help kick off blood clotting are no longer functional in cetaceans, presumably lowering this risk. The rest of the clotting machinery remains intact so whales and dolphins can still seal up injuries.

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Another lost gene—and this one surprised Hiller—encodes an enzyme that repairs damaged DNA. He thinks this change has to do with deep dives as well. When cetaceans come up for a breath, oxygen suddenly floods their bloodstreams, and as a result, so do reactive oxygen molecules that can break DNA apart. The missing enzyme—DNA polymerase mu—normally repairs this kind of damage, but it does so sloppily, often leaving mutations in its wake. Other enzymes are more accurate. Perhaps, Hiller thinks, mu was just too sloppy for the cetacean lifestyle, unable to handle the volume of reactive oxygen molecules produced by the constant diving and resurfacing. Dropping the inaccurate enzyme and leaving the repair job to more accurate ones that cetaceans also possess may have boosted the chances that oxygen damage was repaired correctly.

Cetaceans aren’t the only mammals that returned to the water, and the genetic losses in other aquatic mammals often parallel those in whales and dolphins. For example, both cetaceans and manatees have deactivated a gene called MMP12, which normally degrades the stretchy lung protein called elastin. Maybe that deactivation helped both groups of animals develop highly elastic lungs, allowing them to quickly exhale and inhale some 90 percent of their lungs’ volume when they surface.

Deep-diving adaptations aren’t all about loss, though. One conspicuous gain is in the gene that carries instructions for myoglobin, a protein that supplies oxygen to muscles. Scientists have examined myoglobin genes in diving animals from tiny water shrews all the way up to giant whales, and discovered a pattern: In many divers, the surface of the protein has a more positive charge. That would make the myoglobin molecules repel each other like two north magnets. This, researchers suspect, allows diving mammals to maintain high concentrations of myoglobin without the proteins glomming together, and thus high concentrations of muscle oxygen when they dive.