Biology - Sexuality

The Genetic History of Sex

Three hundred million years ago it was different

October 29, 1999 - BBC

The two chromosomes that determine an animal's sex evolved from an identical pair of ordinary chromosomes about 240 to 320 million years ago.

It is an event, called a genetic hijacking by some scientists, that has profound ramifications today.

Of the 46 human chromosomes, 44 are identical pairs. But two - the X and the Y - are different because they have no perfect match. Embryos with two X chromosomes develop into females, while embryos with an X and a Y chromosome develop into males.

All due to the Y chromosome

David Page, a member of the Whitehead Institute in the United States, wondered how these unique chromosomes first came about.

In a study published in Science, Dr Page and Bruce Lahn report that they have discovered four stages of sex chromosome evolution.

Hundreds of millions of years ago sex was probably determined not by chromosomes, but by some environmental factor, like the temperature at which the egg was incubated. It still happens that way in some animals like crocodiles and sea turtles.

Today the X is home to thousands of genes, but the Y has only a few dozen. Of those, only 19 are shared between the X and Y.

. . .and to two X chromosomes

"These 19 genes are essentially living fossils. They are able to provide scientists with information about the history of sex chromosomes," says Dr Page.

The researchers compared the locations of all 19 pairs of genes on the human X and Y chromosomes. They found that all of these genes are concentrated on the tip of the short arm of the X, whereas they are scattered across the length of the Y.

To their amazement, the scientists found that the genes were clustered into four groups, each group with a different level of sequence similarity. "The most striking observation was that on the X chromosome, the four groups of genes are physically arranged as four consecutive blocks, essentially like the layers of rock are arranged in geological strata," explains Dr. Page. In contrast, the groups appear to be scrambled on the Y chromosome.

By comparing the genes in each stratum with similarities in other mammals, Page and Lahn were able to determine the minimum and maximum ages for all of the strata.

The first strata differentiated 240 to 320 million years ago, shortly after the ancestors of mammals parted company with the ancestors of birds.

The second strata differentiated 130 to 170 million years ago, shortly after our ancestors parted company with the ancestors of the duck bill platypus.

The third strata differentiated 80 to 130 million years ago, shortly after our ancestors parted company with the ancestors of kangaroos.

Finally the fourth and most recent strata differentiated 30 to 50 million years ago, shortly after our ancestors parted company with the ancestors of lemurs.

Each of these events caused an inversion and shuffling of regions of DNA on the Y chromosome so that they could no longer line up with analogous regions of DNA on the X chromosome partner.

This prevented DNA exchange between the similar regions of the two sex chromosomes, and made it possible for portions of the X and Y chromosomes to differentiate from each other.

Genes that are not needed by the male may gradually accumulate causing problematic mutations. "In humans," said Page, "the ramifications of the hijacking are still being played out." , we're just looking within ourselves."

Gene causes infertility

August 21, 1999 - BBC Online

Artificial insemination would be used to weed out the abnormal gene

Scientists have discovered an abnormal gene which sharply reduces sperm production and appears to be a cause of infertility.

The abnormality was found to occur in approximately a quarter of infertile men studied by scientists from Australia and Singapore. The men had no other apparent reason for a low sperm count.

The gene responsible controls the function of a receptor involved in sperm production.

Normally, the receptor detects the presence of the male sex hormone testosterone.

However, the abnormal form of the gene prevents the receptor from sensing the presence of testosterone properly.

The mutation in the gene involved an abnormally high number of repeating units in its make up. The longer the repeat lengths were, the worse was the problem of low sperm production.

Alan Trounson, deputy director of the Monash Institute, where part of the research was carried out, said the cause of most males.

Extreme cases of the repeating units were connected with Kennedy disease, a very severe degenerative neuromuscular disorder which appears in 30 to 40-year-olds.

Researchers are now looking to see if they can stop the transmission of the gene to the children of men who have had IVF (in vitro fertilisation) treatment, especially through the process of intracytoplasmic sperm injection or ICSI.

The process involves injecting a single sperm into an egg and transferring the resulting embryo into a woman's womb.

The scientists are checking for variations in the sperm of men who have the expanded repeating sequence to see if embryos from their sperm could be sorted out on the basis of a normal repeating length.

Dr Amin Gorgy, clinical director of the London Fertility Clinic, described the research as "interesting". However, he said more work was needed before it would be possible to screen out fertile embryos at the IVF stage.

Boys like it hot

July 25, 1999 - BBC Online -

This study is based on meteorological and birth data.

When soaring summer temperatures put the thermometer in the pink, more baby boys are conceived, a German scientist says.

And when winter's chill sinks the mercury into the blue, more baby girls are conceived. Alexander Lerchl of the University of M´┐Żnster has discovered that more boys are born in Germany between April and June, and significantly fewer in October.

Experiments with rats and bats had already hinted that environmental temperatures could affect the sex ratio of offspring, says New Scientist magazine which reports on the unusual study.

Dr Lerchl searched German meteorological and birth records over a 49-year period from 1946 to 1995. He found that sex ratio seemed to correlate with temperature about one month before conception.

Effect on testes

Hot summers or unseasonably warm patches during this period yielded more boys, while unusually cold weather favoured girls. Temperature deviations of just a few degrees centigrade appeared to have an impact. One explanation, says Dr Lerchl, is that temperature affects processes within the testes. He speculates that hot spells may damage sperm carrying an X chromosome more than sperm carrying a Y, so more boys are conceived.

He also speculates that the temperature rise that global warming may bring could further increase the ratio of males to females, which already favours boys by a few per cent. However, there could be a more prosaic explanation for the effect - people have sex more often when it is hot.

Frequent sex increases a woman's chance of conceiving as soon as she ovulates.

Other studies have shown that this results in more sons, possibly because sperm carrying a Y chromosome are faster but less robust than X carriers which stand a better chance if they have to wait for ovulation.

Canadian Study Questions So-Called 'Gay Gene'

Canadian Press - April 22, 1999

Researchers at the University of Western Ontario are questioning a U.S. study that said a gene inherited from mothers influences men's sexual orientation. In 1993, Dr. Dean Hamer and colleagues at the U.S. National Cancer Institute provoked a worldwide furor when they reported they had found evidence of a "gay gene" in men.

They had studied 40 pairs of gay brothers and found 33 of them shared a particular sequence of the genetic codes on their X chromosomes, in an area called Xq28. They said that pointed to a possible gay gene. But in a study published in this week's Science, George Rice and colleagues at Western in London, Ont., said they studied more pairs of gay brothers and found no evidence that they shared some sort of mutation in that area.

"These results do not support an X-linked gene underlying male homosexuality," Rice's team wrote in its report. But the team added that the search should continue for any possible genetic cause of homosexuality. Men, in addition to their 22 pairs of matched chromosomes, have one X and one Y chromosome. Women have two Xs.

Men inherit their X chromosomes from their mothers, and because they have just one copy, are vulnerable to genetic defects carried on the X chromosome such as colour blindness and Fragile X syndrome, which causes a form of mental retardation.

Hamer's team had noted a tendency for homosexuality to run in the female line -- men whose mothers had gay brothers also tended to be homosexual, the team reported. So it looked for an area on the X chromosome that might be involved.

The team homed in on an area known as Xq28.

Rice's team tried to duplicate and expand on those results, studying 52 sets of brothers in Canada who were both gay, looking specifically at the Xq28 gene. "We advertised in Canadian gay news magazines for families in which there were at least two gay brothers," the team wrote.

It compared their genes to samples taken from 33 pairs of brothers who had been gene-tested for multiple sclerosis. But the researchers did not find any particular variation of the gene that marked gays from non-gays. Gay brothers were not unusually likely to share one of four variations of Xq28 that they looked for.

"It is unclear why our results are so discrepant from Hamer's original study," the team wrote. The researchers said it was possible there was another "gay gene," as the team only looked at one gene for its study. But Rice's team also said that if homosexuality was a simple inherited trait, it would be very likely to have been bred out -- because homosexuals would be less likely to have children and pass on the trait.

But studies dating back to the 1980s show some evidence that homosexuality might run in families.

One study on identical twins, who share more of their genes than regular siblings, found one twin was more likely to be gay if his twin was, and another study found homosexual men were more likely to have homosexual brothers even if they were not twins.

Other experts point out that being homosexual does not preclude having children, so there would be no reason for a "gay gene" to have been bred out.