How is it that mammals got shortchanged in the hair cell regeneration department? Birds and mammals split 300 million years ago. Birds share a more recent common ancestor with reptiles. The hair cells of a bird are “scattered in a mosaic all over the surface of the hearing organ,” Andy Groves told the Hearing Restoration conference. Mammals, by contrast, have decreased the number of hair cells and specialized the function of the supporting cells surrounding them. Supporting cells physically position hair cells, Groves explained, and they provide structural integrity to the cochlea to make it mechanically sensitive.
Why would this evolutionary adaptation have occurred? Groves speculates that mammals made a trade-off: in the course of developing high-frequency hearing, their hair cells became more specialized, and in the process they lost the ability to regenerate. Although we humans have devised many ways of inflicting hearing loss on ourselves (such as rock concerts, iPods, and heavy machinery), one of the few naturally occurring things that kills hair cells is the wear and tear of old age. (Unless it turns out that even that is the result of accumulated noise exposure.)
“From an evolutionary point of view,” Groves said, “and this sounds rather brutal, but evolution doesn’t care about old age, as long as you live long enough to have kids.” Once your reproductive years are over, your body has done its evolutionary job. As a result, mammals would not suffer a selective disadvantage by losing the capacity to regenerate their hair cells.
Bruce Tempel, at the University of Washington, echoed that Darwinian opinion. For the past twenty to twenty-five years he has been looking at the genes implicated at one or another level in hearing loss. “Truth be told,” he said in an interview, “the reason that I got really interested in the auditory system is because you don’t need it. From a geneticist’s point of view, basically, this is great. This system can be completely nonfunctional and the animal still survives.” He added that stress and hormonal influences on hearing loss are part of the reason the auditory system is so useful to geneticists: “You’re able to identify the genes, the proteins, and from studying the protein itself find out whether there’s a hormone or an influence on the expression of that protein. You can find out if there are interacting proteins that become a cascade linking the different individual proteins and the genes. And what’s really cool about the auditory system is that we can do all that and still have a viable animal.”
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Andy Groves also studies the genetics of hearing loss. One of the mammalian genes whose function is to stop cells dividing (necessary, to regulate the size of organs and protect against cancer) is the p27 gene, which Jenny Stone talked about at the UW group meeting. Figuring out how to switch off that gene is one of the biggest obstacles researchers face.
After a great deal of work in cell-culture dishes and looking through microscopes, Groves and his colleague Neil Segil discovered that when they isolated mouse supporting cells from the newborn cochlea, the action triggered the p27 gene to switch off and the supporting cells to start dividing. They don’t know why. Unlike humans, mice cannot hear when they are born. By the time they begin to hear—at about two weeks after birth—mouse supporting cells stubbornly refuse to divide even when isolated from the cochlea. Groves, Segil, and their colleagues are now trying to understand what happens to the aging supporting cells that makes them unable to divide.