Y and mighty
It's the chromosome that has for years been relegated to the sidelines of science. But now this tiny cell particle is providing the answers to some very big cultural questions - and putting a match to political time bombs.
It's the runt of the genome. A comma of a chromosome that might be called in evidence to show that the Creator has a feminist sense of humour. It has to be a joke. To design the one chromosome that appears only in male bodies, that sets the developing embryo off on the path of bigger muscles and more aggression, and then to make it such a weedy and insignificant thing.
Not only does it look like an afterthought, but even geneticists have traditionally had little positive to say about the Y chromosome. "There's nothing very interesting on it, is there? Just a few genes coding for sperm," says one researcher, crouched over her computer at the Department of Pathology in Cambridge, investigating the genes involved in breast cancer. "My colleagues thought I was really odd when I started studying it 15 years ago," adds Dr Nabeel Affara, the department's Y expert.
But the runty Y is enjoying the last laugh. Having sand kicked in its face by dismissive researchers will soon be a thing of the past. In recent years, it has been undergoing a Clark Kent-like transformation. A shrimp it may be, but it is turning out to be the wild frontier of the genome, where strange and important things happen.
"There has been almost a century of ignorance and misunderstanding of it," says David Page of the Whitehead Institute in Cambridge, Massachusetts, who is currently working on a major study of the Y. "It has been regarded as a wasteland but I see it more as a natural park with as many unusual features as Yosemite or Yellowstone." Right now, these quirks are providing answers to such very big questions as: where did we come from? How did we develop language? What is it that makes us so different from the apes? Is the sex war hard-wired into our genes?
Y's power to shock has only recently been revealed. There have been reports on the way it can be used to track down the "ancestral" Adam, the one man from whom all males are descended, suggestions that the Native Americans didn't come from Siberia, as all the textbooks say, and, equally controversially, a theory put forward that it is a gene on the Y that accounts for man's ability to speak. What's more, that gene, and a few others nearby, are unique to humans. Although apes have them on the X chromosome, they jumped over to the Y around the time that apes and humans separated. This suggests that Y may hold the secret of what it is that makes us human, which must put the feminist Creator to flight.
But to begin at the beginning, which in the Y's case we can do because we know that there was a time, around 300 million years ago, when there wasn't a Y chromosome. Instead, most animals had a pair of identical Xs and gender was determined by other factors, such as temperature. (In some amphibians, such as turtles and crocodiles, eggs still hatch out as males above a certain point and as females below it.) Then, in one of those dramatic evolutionary transformations that are a feature of the Y, a gene on an X chromosome in a particular mammal mutated. "This mutation became a tyrannical male-determining gene," Page explains. "It said, in effect, 'I will no longer respond to these environmental cues; if I am present, the male pathway will be followed.' "
It survived, but it could do so only by putting a block on the process of swapping genes with the other X of its pair, otherwise it would have been weeded out. Gradually, the X with the rogue gene was able to do less and less trading with its unaltered partner, and took on an identity of its own, as the Y.
These ancient events around its birth conferred on the Y one of the special features responsible for its current stardom: it appears only in males. Any egg that was fertilised by Y-carrying sperm became male; eggs that got the X stayed female. That is why the Y is a unique source of information about the male line. It's a genetic version of those famous biblical begats.
By measuring the differences in the mutations that have crept into the Y, researchers can show that the males of two different ethnic groups are more or less related to a common ancestor. The bigger the differences, the longer they have been separated. Some of the results, reported early last year, were surprising. For instance, the Lemba are a black, Southern African, Bantu-speaking population whose oral tradition says they were originally Jewish. According to their stories, they were once craftsmen in metal who lived in the Yemen. The men would travel south to trade but when a disaster struck back home, some of the men took local wives and settled down. Researchers reported that the pattern of mutations on the Y chromosomes among men of the Lemba was close to that found among a Jewish priestly group known as the Cohens. Similar research suggests that the Israelis and the Palestinians came from a common stock around 7,800 years ago.
Such striking but isolated results suddenly became integrated into a broader picture last November when the whole field of "archogenetics" took a quantum leap forward. A leading science journal, Nature Genetics, published a new human family tree, based on a previously unknown set of variations - haplotypes - on the Y. It confirmed that modern humans had originally migrated out of Africa, but raised what, at first, looked like a ridiculous puzzle. If the dates were correct, the genetic Eve, the one from whom all humans are descended, was 84,000 years older than the genetic Adam, as measured by the Y.
The female equivalent of the Y - genetic information passed only from mother to daughter - is known as mDNA. This is the DNA of the mitochondria, the powerhouse of every cell. For a few years there has been broad agreement that the mitochondrial Eve lived around 143,000 years ago, which seems to make nonsense of the 59,000 years ago that Nature Genetics reported for the "Y-Adam".
In fact, it's not as daft as it seems. What the research shows is that the different chromosomes now found in the human genome were not selected for all at once. Around 143,000 years ago, a variation of mDNA emerged from the pre-human gene pool and proved to be, in computing terms, a "killer application", driving all the others out of business. Like any successful mutation, it popped up in more and more bodies, until all the other versions died out. That's why women today all have variants on the new, improved "Eve" mDNA. The same thing happened with men and the Y, only it took another 84,000 years for the evolution of the super-successful version that eventually wiped the floor with its rivals.
Exactly what it did isn't clear, but it was probably something to do with fertility.
"Something happened to the record between 50,000 and 60,000 years ago," says Peter Oefner, a biologist at the Stanford DNA Sequencing and Technology Centre in California, and an author of the study in Nature Genetics. "We started at ground zero again."
Buried in the paper, and virtually unnoticed by all commentators, is a political time bomb involving the Native Americans. Everyone has seen those pictures of fur-clad mammoth hunters arriving in the virgin territory of North America at the end of the last ice age. The notion that they were the first has always been an important part of Native American mythology, but evidence has been growing that the continent was well-populated long before their arrival. In the past few years, a dozen or so ancient skulls have been unearthed in North America, and not only do they date from a time before the arrival of the mammoth hunters but their shape and proportions have little in common with those of northern Asians. Instead, they look like people from south-east Asia and the Pacific. The issue is politically very sensitive and there have been bitter disputes between Native American groups and various archaeological teams, but genetics is now confirming the story of the skulls.
Two years ago, Douglas Wallace of the Centre for Molecular Medicine at Emory University School of Medicine, based in Atlanta, Georgia, tackled the Native American issue head-on. Working with mDNA, he reported discovering a set of variations known as "haplogroup X" whose implications were dynamite. This X factor is found among Native Americans and among Europeans but not - and this is the important bit - in Siberian groups. Attempts to find it among south-east Asians failed.
The implication of the Nature Genetics paper is that the smoking gun has turned up. Possibly because of the political tensions involved, you have to look hard to find it, but buried at the end of the article is the following: "Native Americans are located between Eurasians and East Asians, indicating common ancestry with both." In other words, they are descended not only from people of the Pacific but from a group that also travelled east and became the founders of European stock. The arrival of Columbus could be seen as just the final stage in a circumnavigation of the globe that had begun 20,000 years earlier.
In a paper published earlier this year, Dr Spencer Wells of the Wellcome Trust Centre for Human Genetics, based in Oxford, who was involved in this research, suggests what might have been going on. "One of the very old Y markers we are studying, known as M45, originally came from southern central Asia around 40,000 years ago," he says. "It looks as if these people are the common ancestor of both the western Europeans and the Native Americans."
But the new tools that are bringing the Y into sharper focus don't just tell us about the movements of ancient people - they can also tell you, if you are a man, how much of your genetic code you share with other men of the same name. "We have found that a person's genotype and their surname are incredibly closely linked," says Professor Bryan Sykes of the Institute of Molecular Medicine in Oxford. The link comes from the fact that men inherit both their name and their Y chromosome from their father. In a preliminary study, investigating the genetic make-up of men called Sykes, the professor found that 50% had the same Y chromosome. That means that for 700 years, since surnames began in England, the Sykes lineage has been largely unbroken. Further research has shown the same proportion for other names, too. One implication is that infidelity, leading to children calling the wrong man Daddy, is not as common as other surveys have suggested. Previous estimates put the figure at between 5% and 10%, while the work on Sykes suggests it is nearer 1%. Another implication is that it may soon be possible to make a guess at the name of a criminal from the traces of DNA he leaves at the scene of the crime.
