Evolution is a master recycler. It often uses old structures (or ancient genes) for new work. The mammalian ear is a perfect example. Over eons, the jaws of our fish ancestors evolved into three separate small bones that transmit sound waves from the eardrum to the inner ear.
Now a new study shows that there was another intervention from fish to mammals. It turns out that the flexible cartilage in fish gills is closely related to the cartilage in the outer ear of mammals, in the visible part of the ear. There is no doubt that flexible cartilaginous structures serve a variety of jobs in fish and mammals: gill structures allow fish to breathe while the cartilage in the outer ears of mammals captures sound. But the underlying gene network that builds these structures has a common history.
To be clear, gill structures did not evolve into the outer ear of mammals. In contrast, when the first vertebrates emerged on land and abandoned their gills, the gene network that made up the gill cartilage was able to build something new. “That’s one of the wonders of life and evolution,” says Abigail Tucker, a professor of development and evolution at King’s College London, who was not involved in the research. “The regulatory network was still there, so it could be co-opted and used again, this time to make an external ear structure rather than a gill.”
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This recycling of the same gene network provided the basis for subsequent evolutionary innovations. The cartilage of the outer ear of mammals took many forms, such as the large and sensitive ears of the echolocating bat, the pointed and sharp ears of a cat, or the floppy ears of an elephant, all of which fit together. sounds that are important to that animal. In some mammals, ear cartilage is even more modified, filled with specialized cartilage cells containing large fat droplets that researchers hypothesize give cartilage unique structural and acoustic properties.
“We think there’s an ancestral program in the head where the cartilage-filled gills moved into position during evolution to connect more closely with the ear, just as ancestral fish jawbones moved into the middle ear,” explains Gage Crump. Stem cell biologist at the University of Southern California and lead author new examwhich was published in nature. “The program to grow a cartilaginous structure in this general area of the head is highly conserved, but the exact position, the entire repertoire of expressed genes and thus the cell types and their functions have varied greatly.”
Crump’s group, which uses zebrafish as a model organism for its research, has long been interested in the development of the vertebrate face. In building an atlas of the different cell types in the zebrafish’s face, the researchers noticed two types of cartilage, one that was expected and one that hadn’t been noticed before. This unexpected shape was a rod of elastic cartilage that supported the finger-like protrusions of the gills. This cartilage was similar to the type found in the outer ear of mammals.
The researchers found that the gene activity of cartilage in the human outer ear was similar to the elastic cartilage in fish gills. But many genes are active in unrelated organs. To see if the structures shared evolutionary history, the researchers focused on promoters, the DNA sequences that drive the activity of their target genes in a specific tissue. They identified six enhancers that were critical for cartilage development in the human outer ear, but not the nose. The researchers reasoned that if gene activity in fish gills and mammalian ear cartilage is driven by similar promoters, it is likely that these structures had the same evolutionary origin.
This developer-focused approach is “very inspiring and very smart, very prudent,” he says Licia Seleristem cell and developmental biologist at the University of California, San Francisco, who was not involved in the research. “This could reveal whether the new structures arose from the use of an ancestral developmental program or appeared de novo.”
To investigate the fish-gill-ear question, the researchers, led by Crump’s then graduate student Mathi Thiruppathy, conducted a series of ingenious genetic transfer experiments. First, they placed the six human outer ear enhancers that control the genes into the zebrafish genome, and used a fluorescent reporter gene that was turned on to identify where in the body the enhancers’ common targets would normally be activated. Strikingly, human ear cartilage enhancers only stimulated green fluorescent protein activity in zebrafish gills, suggesting that what controls gene expression is very similar between the gills and the outer ear, Crump says.
The team then carried out another experiment: they inserted the major promoters active in the zebrafish gills into the mouse genome. There, the researchers found that fish DNA elements activated green fluorescent protein in the outer ear of developing transgenic mice, reinforcing the idea that the same underlying gene network was being used to build cartilage in the gills and ear.
“The part that makes it more interesting than reusing the same molecular tool is that it reuses the regulatory elements (enhancers) that control the expression of these genes,” so the regulatory elements that drive the expression of the genes for cartilage. According to Tucker, the gills drive cartilage gene expression in the mammalian ear. “So it has an additional level of using the system that was there before.”
The researchers then sought to identify the key genes under the influence of these enhancers. It was one gene family that stood out DLX, which is related to a gene identified in the fruit fly distal-less this is important for the development of insect limbs. The researchers found the same promoters for vertebrates DLX Genes appeared over more than 400 million years of evolution from zebrafish to humans. Because of this, the promoters could be exchanged for genetically engineered fish and mice.
To see how old those boosters were, the researchers looked at horseshoe crabs, invertebrates that also breathe with gills. That’s what they discovered distal-less the gene associated with DLX The gene is also involved in making the gills of horseshoe crabs. And by plugging the crab DNA control element into the zebrafish genome, it was possible to activate the fluorescent molecule in the zebrafish’s gills. This suggests that the genetic machinery that makes the mammalian external ear predates the evolution of vertebrates; it may be hundreds of millions of years behind some of the first marine invertebrates with claw-like projections. When fish, the first vertebrates, evolved, the gene network that builds gill cartilage from these invertebrates was recycled to make fish gills, even as fish developed a new type of skeletal skeleton.
“We think the elastic cartilage in our outer ears may be the last vestige of invertebrate cartilage,” Crump speculates.
To understand what happened in the vertebrate evolutionary tree between fish and mammals, the researchers looked at the activity of these enhancers in frogs and lizards. In tadpoles, human external ear promoters activated a fluorescent protein in tadpole gills. In anole lizards, which have no gills or external ears, the human external ear enhancers activated the fluorescent protein in the animals’ ear canal, which also has elastic cartilage similar to that found in the gills of fish and tadpoles. This suggests that the gene network that makes elastic gill cartilage in fish first became active in the ear canal of reptiles and then in the outer ear of mammals.
“So what we imagine is that in amphibians and reptiles, it goes from the gills to the ear canal, and then in mammals, it was massively elaborated to form the outer ear,” Crump says.
During evolutionary time, the cartilage of the outer ear of mammals continued to evolve not only in form but also in internal composition. Cell biologist Maksim Plikus and his team at the University of California, Irvine have recently described cartilage cells in the ears of small mammals—mice, shrews, bats, and rats, among others—that are a cross between cartilage cells and fat cells. These cells, which are filled with fat droplets, form a bubble wrap-like tissue called lipocartilage. Although this tissue was discovered by the German histologist Franz von Leydig in 1854, it was largely forgotten until now. Plikus’ group hypothesizes that lipocartilage has unique acoustic properties, such as the ability to increase the propagation of sound waves, which may be an adaptation for mammalian hearing.
“Although there is a program that exists in invertebrates and then is reused in fish, and in mammals to make the external ear, there are also innovations that appear in mammals,” says Selleri, who wrote one. perspective article in the year science about lipocartilage examination. “One of these innovations is the presence of fatty cartilage.”
“(Lipocartilage) can use the vacuoles (lipid droplets) for a different purpose than what they normally serve,” Plikus says. While the main purpose of lipid droplets in fat cells is energy storage, in lipocartilage, “these lipid droplets mainly play a structural and biomechanical role, so they no longer contribute to metabolic functions,” Plikus says.
Postdoctoral researcher Raul Ramos led the study, which was published in science. The researchers showed that fat vacuoles in mice do not change in response to metabolic state: they do not increase in size when the mouse is overfed, and fat droplets are not used for energy when the animal is starved. The team also showed that the droplets are made using a very specific metabolic pathway that converts sugars into fat, and this controlled metabolic pathway allows the animal’s body to regulate the precise size and spacing of the lipid droplets.
This, in turn, allowed the evolution of ear structures with acoustic properties adapted to the needs of various animal species (the large, spiked ears of bats, for example, are so sensitive that they can detect the flap of a small insect’s wings).
