Y Chromosome, Though Diminished, Is Holding Its Ground

The fear is not without serious basis: The Y and X chromosomes once shared some 800 genes in common, but now, after shedding genes furiously, the Y carries just 19 of its ancestral genes, as well as the male-determining gene that is its raison d’être. So much DNA has been lost that the chromosome is a fraction of its original size.

But there are grounds for hope that the Y chromosome has reached a plateau of miniaturized perfection and will shrivel no more. Researchers led by Jennifer F. Hughes and David C. Page of the Whitehead Institute in Cambridge, Mass., have reconstructed the Y chromosome’s past and find that its gene-shedding days seem to be over. Men are not living on borrowed time after all, they reported on Wednesday in the journal Nature.

In people, sex is determined by a single gene that resides on the Y chromosome. Chromosomes come in pairs, with one set bequeathed by each parent, and the Y is paired with X such that men have an X-Y pair and women an X-X. When the male-determining gene first arose, some 320 million years ago, the X and Y were both full-length chromosomes, each bearing the same set of 1,000 or so genes.

The Y chromosome began its self-sacrificing downsizing in the gallant cause of protecting women. As is well known, the purpose of sex is to exchange DNA between the mother’s and father’s version of each gene, creating novel combinations that will help children adapt to a new environment better than their parents did. So before generating sperm and eggs, the two members of each pair of chromosomes line up side by side and swap large chunks of DNA.

But the male-determining gene on the Y cannot be allowed to sneak across onto the X because it would insert maleness where it should not be. So a no-swapping zone was created around the male-determining gene. That inhibitory zone was extended in five stages until it covered the whole of Y chromosome except its very tips.

Genes at the tips of the Y exchange DNA with the X in the usual way, but all those in between were condemned to a monklike existence. And being unable to innovate, most of these genes became first antiquated and then dispensable. The X chromosome now has 790 genes in its no-swap zone, according to best current estimates, but the Y retains a mere 19 of these original genes.

As the only part of the human genome that never passes through a woman’s body, the Y is the ideal refuge for male-favoring genes, especially those having to do with sperm production. Eight such genes have leapt onto the Y from other chromosomes, bringing its total score to 27. But these few additions have not allayed concern about the chromosome’s long-term viability.

The Whitehead team’s new report provides solid assurance by showing that the Y’s shedding of genes is not a continuing process. Almost all of its genetic self-sacrifice occurred in the distant past.

This insight was gained by decoding the Y chromosome of rhesus monkeys, which shared a common ancestor with humans at the time, and retain 20 ancestral genes, meaning those that have a counterpart gene on the X. Only one of these genes has been lost in humans at some time in the last 25 million years, showing that the Y chromosome became essentially stabilized long ago.

“It’s my sincere hope that this article might put the notion of the disappearing Y chromosome to rest,” Dr. Page said.

He and his colleagues have reconstructed the entire history of the Y chromosome, showing that its no-swap zone expanded in five stages, of which the first began 320 million years ago and the last ended 29 million years ago. Each stage was caused when a chunk of DNA fell out of the Y chromosome and was accidentally flipped the wrong way when it was patched back in, so it would no longer line up correctly with its counterpart region on the X. At each stage, loss of genes was precipitous at first but then leveled off.

The first stage originated to fence in the male-determining genes. The driving force for creating more no-swap zones was probably the existence of genes in nearby regions that were beneficial for males and detrimental for females, Dr. Page said. Sexually antagonistic genes probably exist throughout the genome, but only on the Y chromosome can the male-favoring ones gain protection.

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Y Chromosome Can Raise Heart Disease Risk by 50 Percent

Image courtesy of iStockphoto/luckyraccoon

Men tend to get coronary artery disease much earlier than do women. For some men, the reason for that might be in part because of their fathers and their father’s father according to a new study, published online Wednesday in The Lancet.

The study analyzed data from 3,233 unrelated white men enrolled in previous U.K. studies. From this information, the researchers took a close look at genetic markers on the Y chromosome, which is passed on from father to son. They found that 15 to 20 percent of the men fell into one of the 13 ancient ancestry branches known as haplogroup I.

Men in this haplogroup, who all showed a common variant on the Y chromosome, were 50 percent more likely to have coronary artery disease than those without it even when age, body mass, cholesterol, high blood pressure, smoking and other risk factors were taken into account. The genetic link is not entirely surprising, given that heart disease has been known to run in families, but the finding adds support to previously observed trends and insights into additional lines of research.

The finding follows well-described geographic distribution of coronary artery disease. Haplogroup I has been traced back to hunter-gatherers who arrived in Europe from the Middle East some 25,000 years ago and who today remain more prevalent in the northern areas of western Europe, where incidence of coronary artery disease is still higher than it is in the south where the haplogroup R1b1b2 is more common.

The genetic variant came with altered patterns of regulation in 19 key pathways all of which were linked to immune and inflammatory responses. These differences might play a role in atherosclerosis, or the hardening of the arteries, noted the researchers, who were led by Fadi Charchar, of Australia’s University of Ballarat. “Dysfunction of immune response is a well established contributor to atherosclerosis and coronary artery disease,” they wrote. Previous research had found other immuno differences in men from this haplotype, such as HIV-positive men in this group taking longer to show an immune response after getting antiretroviral therapy.

The findings do not suggest that heart disease risk for men is entirely or even mostly lodged on the Y chromosome. And the researchers noted that knowing which haplogroup a man is from is unlikely to yield predictions of his individual risk of coronary artery disease. But, as they pointed out, a better understanding of this widespread association “could have important public health implications,” especially in attempts to assess the prevalence of the disease within a population. And further study should help “to decipher complex interplay between human Y chromosome, immunity and cardiovascular disease,” the researchers wrote.

“These findings are exciting,” Virginia Miller of the Mayo Clinic wrote in an associated Lancet essay (Miller was not involved in the new research). The new work also suggests that there could be another side to the genetic equation that is protective, she added.

Follow Scientific American on Twitter @SciAm and @SciamBlogs. Visit ScientificAmerican.com for the latest in science, health and technology news.
© 2012 ScientificAmerican.com. All rights reserved.

View the original article here

Y Chromosome Can Raise Heart Disease Risk by 50 Percent

y_chromosome_heart_disease Image courtesy of iStockphoto/luckyraccoon

Men tend to get coronary artery disease much earlier than do women. For some men, the reason for that might be in part because of their fathers and their father’s father according to a new study, published online Wednesday in The Lancet.

The study analyzed data from 3,233 unrelated white men enrolled in previous U.K. studies. From this information, the researchers took a close look at genetic markers on the Y chromosome, which is passed on from father to son. They found that 15 to 20 percent of the men fell into one of the 13 ancient ancestry branches known as haplogroup I.

Men in this haplogroup, who all showed a common variant on the Y chromosome, were 50 percent more likely to have coronary artery disease than those without it even when age, body mass, cholesterol, high blood pressure, smoking and other risk factors were taken into account. The genetic link is not entirely surprising, given that heart disease has been known to run in families, but the finding adds support to previously observed trends and insights into additional lines of research.

The finding follows well-described geographic distribution of coronary artery disease. Haplogroup I has been traced back to hunter-gatherers who arrived in Europe from the Middle East some 25,000 years ago and who today remain more prevalent in the northern areas of western Europe, where incidence of coronary artery disease is still higher than it is in the south where the haplogroup R1b1b2 is more common.

The genetic variant came with altered patterns of regulation in 19 key pathways all of which were linked to immune and inflammatory responses. These differences might play a role in atherosclerosis, or the hardening of the arteries, noted the researchers, who were led by Fadi Charchar, of Australia’s University of Ballarat. “Dysfunction of immune response is a well established contributor to atherosclerosis and coronary artery disease,” they wrote. Previous research had found other immuno differences in men from this haplotype, such as HIV-positive men in this group taking longer to show an immune response after getting antiretroviral therapy.

The findings do not suggest that heart disease risk for men is entirely or even mostly lodged on the Y chromosome. And the researchers noted that knowing which haplogroup a man is from is unlikely to yield predictions of his individual risk of coronary artery disease. But, as they pointed out, a better understanding of this widespread association “could have important public health implications,” especially in attempts to assess the prevalence of the disease within a population. And further study should help “to decipher complex interplay between human Y chromosome, immunity and cardiovascular disease,” the researchers wrote.

“These findings are exciting,” Virginia Miller of the Mayo Clinic wrote in an associated Lancet essay (Miller was not involved in the new research). The new work also suggests that there could be another side to the genetic equation that is protective, she added.

Follow Scientific American on Twitter @SciAm and @SciamBlogs. Visit ScientificAmerican.com for the latest in science, health and technology news.
© 2012 ScientificAmerican.com. All rights reserved.

View the original article here

Y Chromosome Can Raise Heart Disease Risk by 50 Percent

y_chromosome_heart_disease Image courtesy of iStockphoto/luckyraccoon

Men tend to get coronary artery disease much earlier than do women. For some men, the reason for that might be in part because of their fathers and their father’s father according to a new study, published online Wednesday in The Lancet.

The study analyzed data from 3,233 unrelated white men enrolled in previous U.K. studies. From this information, the researchers took a close look at genetic markers on the Y chromosome, which is passed on from father to son. They found that 15 to 20 percent of the men fell into one of the 13 ancient ancestry branches known as haplogroup I.

Men in this haplogroup, who all showed a common variant on the Y chromosome, were 50 percent more likely to have coronary artery disease than those without it even when age, body mass, cholesterol, high blood pressure, smoking and other risk factors were taken into account. The genetic link is not entirely surprising, given that heart disease has been known to run in families, but the finding adds support to previously observed trends and insights into additional lines of research.

The finding follows well-described geographic distribution of coronary artery disease. Haplogroup I has been traced back to hunter-gatherers who arrived in Europe from the Middle East some 25,000 years ago and who today remain more prevalent in the northern areas of western Europe, where incidence of coronary artery disease is still higher than it is in the south where the haplogroup R1b1b2 is more common.

The genetic variant came with altered patterns of regulation in 19 key pathways all of which were linked to immune and inflammatory responses. These differences might play a role in atherosclerosis, or the hardening of the arteries, noted the researchers, who were led by Fadi Charchar, of Australia’s University of Ballarat. “Dysfunction of immune response is a well established contributor to atherosclerosis and coronary artery disease,” they wrote. Previous research had found other immuno differences in men from this haplotype, such as HIV-positive men in this group taking longer to show an immune response after getting antiretroviral therapy.

The findings do not suggest that heart disease risk for men is entirely or even mostly lodged on the Y chromosome. And the researchers noted that knowing which haplogroup a man is from is unlikely to yield predictions of his individual risk of coronary artery disease. But, as they pointed out, a better understanding of this widespread association “could have important public health implications,” especially in attempts to assess the prevalence of the disease within a population. And further study should help “to decipher complex interplay between human Y chromosome, immunity and cardiovascular disease,” the researchers wrote.

“These findings are exciting,” Virginia Miller of the Mayo Clinic wrote in an associated Lancet essay (Miller was not involved in the new research). The new work also suggests that there could be another side to the genetic equation that is protective, she added.

Follow Scientific American on Twitter @SciAm and @SciamBlogs. Visit ScientificAmerican.com for the latest in science, health and technology news.
© 2012 ScientificAmerican.com. All rights reserved.

View the original article here