May 2014

The Y chromosome is finally getting the respect it deserves. Since the early 1900s, we’ve known that the Y chromosome is responsible for making males—XX embryos develop into girls and XY embryos develop into boys—but the Y was thought to do little else. After all, at just one quarter the length of the X chromosome, the Y is relatively puny. Biologists hypothesized that the few genes it does carry contribute to processes like sperm production and testes development by helping turn on and off other genes. In fact, the Y had such a bad rap that many researchers suggested that it was on its way to evolutionary extinction. However, now, new research suggests that the Y chromosome is here to stay. Its function goes far beyond triggering maleness…

Where's the evolution?

To understand why the Y chromosome is the way it is, one needs to know a little about its evolutionary history. The evolution of our modern Y chromosome hinges on recombination, the cellular process in which pairs of chromosomes swap corresponding bits of their DNA with one another. Recombination is what gives chromosomes variety and what makes, for example, the version of chromosome 18 that you inherited from your mother not an exact copy of your maternal grandmother’s or grandfather’s but a combination of them both.

One hundred and eighty million years ago, the Y chromosome of placental mammals was the same as our X chromosome, and sex was determined by other means, perhaps by environmental triggers such as temperature (as is the case in some turtles, lizards, and snakes today). These two proto-sex-chromosomes underwent recombination in the same way that our other chromosomes do. Then a male-determining gene originated on the would-be Y, and the two chromosomes started to diverge from one another. Once the Y started to become specialized for male genes, recombination between the X and Y became detrimental for individuals because the process sometimes mixed up the sex-determining genes. Any individual whose cells repressed recombination between the X and Y would have had a fitness advantage over others. Through natural selection, this genetic characteristic spread throughout the ancestral mammal population.

Ultimately, this process resulted in Y chromosomes that barely recombined with the Xs at all—just a little near the tips of the chromosomes, enough to keep cell division orderly, but not enough to move genes bits from one chromosome to the other. Of course, in females (bearers of two X chromosomes), the Xs could still recombine with another X. It was only in males that repressed recombination was advantageous. This innovation worked well for keeping sex determination straight, but it also had a detrimental side effect for the integrity of the Y chromosome.

The problem was mutation. Because mutations occur randomly, they have a wide variety of effects—some are helpful to their bearers, others have no effect, and still others are harmful. In fact, the vast majority of mutations are either neutral or harmful. What happens if a harmful mutation occurs on a chromosome that also carries well-adapted genes and a helpful mutation or two? Are the helpful mutations and the well-adapted gene versions evolutionarily doomed because they are now physically connected to a harmful mutation? If there is no way to decouple harmful mutations from good genes, mutations can build up in a population over time, offsetting the benefit of advantageous gene versions and dragging the fitness of the entire population down. This concept is called Muller’s ratchet or genetic load.

Recombination allows chromosomes to escape Muller’s ratchet. Through recombination, segments of chromosomes get broken up, and helpful gene versions can wind up together, free of their detrimental brethren, and spread through a population. But of course, most of the Y chromosome doesn’t undergo recombination, opening the door for Muller’s ratchet. Once the Y stopped recombining, it accumulated mutations that wound up deactivating most of its genes. Today, the Y chromosome contains only 3% of the functioning genes that it once did! This observation led some researchers to suggest that the Y was on its way to full extinction. However, recently published research contradicts this idea.

Last month, two different research groups published studies that explore the function of the genes still present on the Y chromosome and that compare the human Y chromosome to those of other mammalian species. They found that even distantly related species share most of the same functional Y chromosome genes, suggesting that the species have not continued to lose genes since they shared a common ancestor many millions of years ago. Furthermore, studies of these retained genes showed that many of them were expressed all over the body and seemed to be protected by strong natural selection. These findings imply that Muller’s ratchet acted quickly after recombination slowed, ruining many genes in short order, but that this loss wasn’t random. Less important genes were lost, but the process halted with a few key genes. These genes have not degraded in tens of millions of years and aren’t poised to do so. They seem to be so important that mutations in them can’t accumulate because any individual with a mutation damaging one of these genes would die or be unable to reproduce. Our X chromosomes also contain copies of these genes (females need them just as much as males do!)—but they are so important that a half dose just won’t do. XX individuals get a half dose of the gene from each of their X chromosomes, and XY individuals get a half dose from their X and a half dose from their Y.

These genes are control genes. They turn on and off cascades of other genes that must be expressed in many different cells of the body. In fact, many of these genes are among the first to be activated just after egg meets sperm, even before a developing embryo has implanted in its mother’s uterus. This turns our previous view of the Y chromosome on its head. Yes, the Y contains genes needed for sex determination—but it also contains many control genes that are critical for survival in general and go far beyond the development of sex organs and sperm production. The Y’s list of genes is short, but very sweet—and so this bearer of masculinity is not evolving away anytime soon!