The genome of cetaceans helps tell the story of mammals' return to aquatic life.
About 400 million years ago, the ancestors of all four-limbed creatures first set foot on land. Fast forward to about 350 million years ago, and the descendants of these early terrestrial animals made a 180-degree turn: it returned to the water. Over time, creatures that returned to the sea gave rise to animals very different from their terrestrial counterparts: they became the magnificent whales, dolphins and porpoises that glide through the ocean today.
Over a period of about 10 million years, the return to aquatic life is a drastic transformation that will alter animals from the inside out. But evolutionarily speaking, this is only a blink of an eye. This group of animals, now known as "cetaceans", lost their hind limbs and lost almost all of their hair due to a powerful environmental shift. Their bizarre body structure has puzzled paleontologists for decades, who speculate that they may have originated from a variety of creatures, including marine reptiles, seals, marsupials such as kangaroos, and even a group of now-extinct wolf-shaped carnivores.
"In general, cetaceans are the peculiar and perverse of mammals," one scientist wrote in 1945.
Then, in the late '90s, genetic data confirmed that whales and cattle, pigs and camels were part of the same evolutionary lineage — a clade called cloven-hoofed orders. Later, fossils from modern India and Pakistan enriched this family tree, identifying the closest ancient relative of cetaceans as a small wading deer.
But their anatomy is just the beginning of the strange appearance of cetaceans. To survive in the sea, they must also undergo internal modifications, altering their blood, saliva, lungs and skin. These changes are not evident in fossils, and cetaceans are not easily studied in the laboratory. Instead, it was the genes that allowed them to surface again.
As cetacean genomes continue to grow, geneticists can now look for molecular changes that accompany the transition back into the water. While it's impossible to pinpoint the effects of any particular mutation, scientists suspect that many of the mutations they see correspond to the adaptations of cetaceans diving and breeding in deep blue oceans.
Dive into the deep sea
The first cetaceans lost more than legs when they returned to the water: their entire genes lost function. Of the large number of genetic letters that make up the genome, these failed genes are among the most detectable changes. They are like a jumbled or fragmented sentence that no longer encodes for an entire protein.
This loss can occur in two ways. Perhaps having a particular gene is harmful to cetaceans, so animals that lose this gene gain a survival advantage. Michael Hiller, a genomist at the Senkenburg Institute in Frankfurt, Germany, believes it could also be a "don't use or lose" situation. If the gene doesn't do anything in the water, it accumulates mutations at random, and even if it no longer works, the animal is no worse.
Michael Shearer and his colleagues delved into the return to aquatic transformation by comparing the genomes of four cetaceans (dolphins, orcas, sperm whales, and minke whales), as well as the genomes of 55 land mammals plus a manatee, a walrus and a Weddell seal. The team reported in the journal Science Advances in 2019 that about 85 genes lost function when cetacean ancestors adapted to the ocean. In many cases, Shearer says, they can guess why these genes fail.
For example, cetaceans no longer possess a specific gene: SLC4A9, which is associated with the production of saliva. This makes sense: what good is saliva when your mouth is already full of water?
Cetaceans also lost four genes involved in the synthesis and response of melatonin, a hormone that regulates sleep. The ancestors of whales may have quickly discovered that if they shut down their brains for hours at a time, they couldn't surface to breathe. Modern cetaceans shut down only one brain hemisphere per sleep, and the other remained awake. "If you no longer sleep as regularly as we know, then you probably don't need melatonin," Shearer said. ”
Whales have to hold their breath for long periods of time to dive and hunt, which also appears to stimulate genetic changes. Divers know that deep diving means nitrogen bubbles forming in the blood, which can be harmful to early cetaceans. It just so happens that in cetaceans, two genes that normally help blood clot (F12 and KLKB1) no longer work, presumably reducing this risk. The rest of the clotting mechanism remains intact, so whales and dolphins can still seal the wound.
Another missing gene, which surprised scientists, encoded an enzyme that repairs damaged DNA. He believes this change is also related to deep diving. When cetaceans surface to breathe, oxygen suddenly rushes into their bloodstream, and as a result, reactive oxygen molecules that can break down DNA are flooded. The missing enzyme (DNA polymerase Mu) usually repairs this type of damage, but it is sloppy and often leaves mutations. Other enzymes are more precise. Perhaps the "DNA polymerase Mu" is too sloppy for the cetacean lifestyle to handle the large number of reactive oxygen molecules produced by constantly diving and floating. Abandoning inaccurate enzymes and leaving the repair to more accurate enzymes that cetaceans also possess may increase the chances that oxygen damage will be repaired correctly.
Of course, cetaceans aren't the only mammals returning to the water, and the genetic losses of other aquatic mammals are often similar to those of whales and dolphins. For example, both cetaceans and manatees have deactivated a gene called MMP12, which normally degrades elastin. Perhaps this inactivation helped both groups of animals develop highly elastic lungs, allowing them to exhale and inhale quickly, about 90 percent of their lung volume, when they surfaced.
However, adaptation to deep-sea diving is not all about loss. One obvious advance is in genes that carry instructions for myoglobin, a protein that supplies oxygen to muscles. Scientists examined the myoglobin gene in diving animals, from small otters to giant whales, and found a pattern: In many diving animals, the protein has more positive charges on its surface. This will make the myoglobin molecules repel each other like two northern magnets. The researchers suspect that this allows diving mammals to maintain high concentrations of myoglobin without aggregating the proteins and thus maintaining higher concentrations of muscle oxygen while diving.
Pressure on pathogens
Early cetaceans faced another challenge when they started swimming: billions of tiny bacteria. In contrast to air, aquatic environments are a chowder of viruses, bacteria, and other pathogens that try to sneak into whales through their skin and lungs. "It's a living environment," said Nathan Clark, an evolutionary geneticist at the University of Utah in Salt Lake City. "Everything that faces the outside environment is more vulnerable to pathogens." He believes that these marine bacteria stimulate genetic changes that affect the skin and lungs of mammals that return to the ocean.
Clark and his colleagues found these skin and lung changes when they examined the DNA of cetaceans, manatees, dugongs and pinnipeds (seals, walruses and sea lions). They looked for cases in which a particular gene seemed to accumulate DNA changes faster or slower in all aquatic mammals than in land mammals. This pattern tells them that genes face strong evolutionary pressure as aquatic organisms adapt to the ocean.
Researchers reported in 2016 that they found hundreds of genes that showed this pattern in these three different aquatic populations. Under such evolutionary pressure, genes include genes that code for proteins in the skin, as well as genes that code for liquid surfactant that covers the inside of the lungs. It's hard to know exactly how these genetic changes make the animals' physiology better, but evolutionary geneticist Nathan Clarke's best guess is to protect them from bacteria.
Not surprisingly, when the cetaceans returned underwater, the genes of the immune system also changed. Andrea Cabrera, an evolutionary biologist at the University of Copenhagen, says that, in fact, this is a common pattern of evolution. Every time you change the environment, you have to adapt to the new composition of pathogens and microorganisms. Cabrera co-authored the 2021 Perspectives on Genetics and Cetacean Evolution in the Annual Review of Ecology, Evolution and Systematics. Chinese scientists have even found that a special bacterial sensor in dolphins responds less efficiently to terrestrial bacteria than the corresponding protein in cows.
When Nathan Clark specifically screened for genes that cetaceans, manatees and pinnipeds lost when they returned to the water, his number one discovery was a gene called "PON1." The function of the protein it encodes is not fully understood, but Clark suspects that inactivating it could protect cetaceans from inflammation, which occurs when holding their breath for long periods of time.
When cetaceans first return to the ocean, it is good to inactivate the PON1 gene. But today, a functional PON1 gene might come in handy. In mammals, it encodes the main enzyme that can degrade toxic organophosphorus pesticides. Insects lack PON1, so they are susceptible. We humans and other land mammals are protected to some extent. "If these marine mammals lose it, if they roam like manatees near agricultural runoff and canals, it could be a fatal problem," Clark said. ”
Sensory systems
Nathan Clark and other scientists also observed a significant reduction in the function of cetaceans' olfactory and taste genes — in one study, toothed whales had nearly 80 percent fewer olfactory genes. Land mammals have hundreds of olfactory receptors that allow them to discern a wide variety of odors, but these receptors work in air, not in water. (They differ from the underwater sensory systems used by fish such as sharks.) ）
Presumably, cetaceans did not get any benefit from the receptor, so they lost the receptor. This coincides with anatomical changes. The olfactory structure of fin whales such as humpback whales is very weak, while toothed whales such as killer whales are completely absent. If you swallow the food whole, the taste will not seem so useful. Cetaceans no longer have genes that perceive sour, sweet, umami, or most bitter tastes.
They're not the only ones who have had such a bland experience with seafood. Other marine mammals back in the water, even non-mammals, have experienced similar genetic losses. Penguins have fewer intact olfactory receptor genes than other waterbirds, and their taste receptor genes suggest that they have lost their ability to sense sweet, bitter, and umami tastes, leaving only sour and salty. Takushi Kishida, an evolutionary geneticist at the Shizuoka Prefecture Museum of Natural and Environmental History in Japan, even found that when sea snakes wriggle back into the water, they also lose several olfactory receptor genes.
In the depths of the sea is not only impossible to smell, but also very dark. So it's not surprising that cetaceans change some of their visual genes. Most mammalian eyes have a light sensor called a rod for low-light, colorless vision, as well as two types of cones, one for green light and one for blue light. (Humans have an extra cone for red.) As cetaceans evolved, rod-shaped sensors changed in their genes to be more sensitive to blue light — perfect for the deep blue depths. There have also been several cases in which animals have lost one or two cones. Some cetaceans, such as beluga whales and orcas, still retain blue cones. Others, such as sperm whales, have neither cones nor complete monochromatic vision.
Scientists know they are just beginning to explore the genetic depth of cetacean evolution. Now, with dozens of cetacean genomes to study, and new analytical techniques being developed, they are poised to further explore the transformation of aquatic animals, as well as other exciting moments in cetacean evolutionary history. Dolphins themselves offer a plethora of questions: how did they diversify to such a variety that they make up nearly half of today's cetacean species. How did they and other toothed whales learn echolocation, navigating the ocean through sound? How did dolphins' brains become so large that the brain-to-body ratio is comparable to that of great apes?
The scientists said: "Most important problems remain unsolved. ”
The evolution of Super Bull (Don't laugh!) This is a serious popular science book on biological evolution! ¥24.9 for purchase
If friends like it, stay tuned to "Know the New"!