Featured Articles

Put in on the bill

By Sanjida O'Connell, Guardian

4 April 2000: The first one brought to England was believed to be a fake. Who but a bad taxidermist with a warped imagination would stick four webbed feet and a duck's bill onto a furry stoat-like body?

The platypus, evolution's own brand of magical realism, not only exists, but could, with the help of another Australian oddity, the opossum, help shed light on sex wars, genes and cancer.

When Dr Randy Jirtle, from Duke Medical Center, Durham, North Carolina, examined genetic material from a platypus he was looking for an absence of evidence, an absence of imprinted genes to be precise.

Normally animals receive one copy of every gene from both their parents, but recently scientists have discovered a class of genes which don't obey the rules. These are imprinted: either the mother's or father's copy is shut down. It's a battle of the sexes that begins at conception for the father wants the foetus to grow large, while the mother doesn't want the foetus to be too big to pass through the birth canal or to drain too much energy from her.

Genetic imprinting is thought to be involved in muscle growth, as well as brain development and sexual orientation. Homosexuality and transsexuality could be due to imprinting defects according to Dr Richard Green, from the department of psychiatry at Charing Cross Hospital, London, who worked with Barry Keverne from the department of animal behaviour at Cambridge University.

The hypothesis is that male to female transsexuals inherit one or more imprinted genes from their mother which have a feminising effect.

But back to the platypus: Dr Jirtle and his colleague Dr Keith Killian chose to look at this beast because they thought there should be no sex wars among the platypuses. By a bizarre twist of fate, they are monotremes: they look like mammals but lay eggs. Opossums, the other animal he and his team examined, are marsupials and have a refreshingly short pregnancy which lasts 13 days.

The foetus is then nursed in the mother's pouch. Jirtle's theory was that neither marsupials nor monotremes should have imprinted genes because there was no need for the sexes to battle for resources if the foetus grows in either an egg or a pouch. However, what he and his colleagues discovered was that opossums but not platypuses do have imprinted genes. The imprinted gene from the father causes the young opossums to develop rapidly. This supports the idea that imprinting is the result of a sexual battle, says Jirtle.

"Young opossum must crawl to reach the pouch and latch on, and this is consistent with a battle of the sexes for nutrient allocation as a reason for imprinted genes. For the opossum, it's literally a race for life."

Once newborn opossums latch on to the mother's nipple, the nipple swells and the babies are stuck there for months until their mouths become big enough to open. Since there are only a dozen nipples and up to 50 babies in a single litter, competition is high. The faster a baby opossum can climb, the more likely it is to survive, and the more likely its genes will be passed on. On the other hand, each platypus has an egg to itself, and once the eggs hatch, there's enough to go round: the mother platypus lacks nipples and milk oozes freely from patches on her chest. There are about 30 known imprinted genes, but according to Jirtle, there could be as many as 500.

"We don't know if humans need these imprinted genes, or if we would be okay without them," Jirtle says, "Although this battle of the sexes occurred about 150 million years ago, it's like keeping stuff in the freezer - you jam it in and leave it there even if it's no longer useful. Nevertheless, we have imprinted genes and they are targets for developmental diseases and cancer."

We have only one copy of each imprinted gene because one parental copy is suppressed. If this remaining copy mutates, or is damaged there's no handy back-up.

"A single mutation in a gene for growth can cause cells to develop abnormally and become cancerous. The imprinted gene in the opossum has the cumbersome title of M6P/IGF2 receptor. This gene exists in humans too, and is a tumour suppressor, but is not imprinted. However, even though we have two copies of the gene, it is still implicated in the early stages of cancer: at least one copy of this gene doesn't work in more than 60% of liver cancers, 30% of breast cancers and 50% of lung cancers. Like the opossum, and unlike us, mice do have an imprinted copy of the growth gene.

"It's a funny gene," says Jirtle. "It's the only gene presently known that is imprinted in mice, but not humans."

Jirtle's next plan is to try and develop a mouse that has two copies of the gene. This would make genetically modified mice more similar to humans in their response to carcinogenic agents and thus would be better models to use in cancer research. Ultimately once he and other researchers in the field understand the molecular genetics behind imprinting, they may be able to help treat not only cancer, but a whole range of other disorders. Angelman syndrome, for instance, is a disease caused by the mutation of a maternal expressed imprinted gene which results in retardation, insomnia, seizures and hyperactivity.

Jirtle also believes that the research so far can help us retrace our evolutionary origins. The presence of imprinted genes in the opossum but not platypus suggests that marsupials are more closely related to eutherians - mammals whose offspring develop in the womb - than they are to the egg-laying monotremes. According to his research, the platypus evolved earlier than the opossum.

"When did the imprinting of this gene start and end?" asks Jirtle. "I want the whole family tree known for this gene."