Lowly Y chromosome may deserve some respect after all

Yes, the Y chromosome separates the guys from the gals, but scientists didn't think it was good for much else. New research indicates that in humans the Y includes a set of multitasking genes that regulate cells throughout the male body.

The chromosome that separates males from females appears to play a much larger role in humans than just determining who gets what set of reproductive plumbing. It also carries a hardy set of genes that regulate functions in every cell throughout a male's body, as well as the behavior of genes throughout his genome.

That is the implication of two new studies that look at the evolution of the Y chromosome, which has retained a small set of genes that have survived millions of years of evolution.

Indeed, "it looks like the Y has the potential to do a lot of regulation, from the earliest stages of development right after fertilization all the way to adulthood in every tissue," says Winston Bellott, a researcher at the Whitehead Institute at the Massachusetts Institute of Technology in Cambridge, Mass., and the lead author of one of two papers on the topic set for publication Thursday in the journal Nature.

As researchers dig deeper into the actions of these genes, the results also could help explain why some diseases are more prevalent in men or women or why their responses to the same disease differ, he adds, providing insights for new therapies.

That's quite a role change for the once-lowly Y. For years, researchers viewed the Y chromosome as a genetic wasteland, good for little else but serving up a male reproductive system. Since then, researchers have found that the Y chromosome holds some important genes, but even these were related to male fertility.

Moreover, the Y chromosome's tumultuous evolutionary history prompted predictions that the chromosome, and perhaps men, would vanish in a few million years. Some 300 million years ago, the X and Y chromosomes shared a common collection of genes, from which they diverged. X chromosomes today have retained some 98 percent of these original genes, while the Y chromosome has retained a scant 3 percent of these common ancestral genes.

Yet that 3 percent represents a tenacious bunch.

Two years ago, another member of Dr. Bellot's team, which included 29 researchers from three institutions in the US, published a comparison of Y chomosomes from humans with those of chimpanzees and rhesus macaques. The comparison showed that the human version lost one ancestral gene some 25 million years ago, when the lineage of mammals that would lead to humans diverged from those that would lead to rhesus macaques, but then stabilized to retain its current complement.

In this latest study, the team added increasingly remote mammalian relatives – marmosets, mice, rats, bulls, and opossum – essentially to the base of the mammal family tree. In addition, the team analyzed chromosomes from chickens.

Chickens? Birds have chromosomes that allow researchers to see what the X and Y chromosomes were like before they diverged.

"Looking at the chicken is like getting the passenger list for the Titanic when it left England," Bellot says. "Each of these Y chromosomes is like looking at a different life boat to see who got picked up."

In this case, the persistent survivors are 36 ancestral genes on the Y chromosomes across each of the mammals in the sample that have a comparable gene on the X chromosomes.

A second team, led by University of Laussane researcher Henrik Kaessmann, analyzed the Y chromosomes from 15 mammals across a wider range of mammals and traced the origins of the Y chromosome as far back as 180 million years ago, when placental mammals and marsupials diverged. Theirs is the other paper appearing in Thursday's Nature.

Two genes in particular survived in placental as well as marsupial mammals, Bellott explains, suggesting that "the genes survived because they were special and not because they were just lucky."

It turned out that the survivors were important to key biological processes in mammals.

"They are expressed across more tissues across more developmental stages" than the genes that vanished, Bellott says. "And they seem to be regulators of many more genes" than were governed by the genes that didn't survive.

In a sense, he says, the Y chromosome became more streamlined, with evolution stripping it to its essentials, rather than randomly growing increasingly degenerate over time.

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