First Decoded Marsupial Genome Reveals "Junk DNA" Surprise

Stefan Lovgren
for National Geographic News
May 10, 2007
The genome of a marsupial—the tiny short-tailed opossum (Monodelphis domestica)—has been sequenced for the first time.

The study reveals a surprising role in human evolution for "jumping genes"—parasitic bits of "junk DNA" that until now were thought to be nothing more than a nuisance—and may also lead to a number of medical breakthroughs.

In particular, the study highlights the genetic differences between marsupials such as opossums and kangaroos and placental mammals like humans, mice, and dogs.

Marsupials typically spend their youths tucked in a mother's pouch, while placental females maintain a temporary organ called the placenta to nourish their embryos.

"The opossum is a wonderful comparison to the human," said Eric Lander, director of the Broad Institute of MIT and Harvard University in Cambridge, Massachusetts, which led the sequencing project.

The study, which appears in today's issue of the journal Nature, helps to explain the evolutionary origins of human DNA, Lander pointed out. (Read a genetics overview.)

And opossums are often used as models in a wide variety of research on human health and disease, including the malignant melanoma form of skin cancer. (Related: Macaque Genome Deciphered; May Herald Medical Breakthroughs" [April 12, 2007].)

The new findings show that marsupials have a much more complex immune system than previously thought.

Jumping Genes

Marsupials are the closest living relatives of placental mammals. The two groups split from a common ancestor about 180 million years ago.

Scientists were able to pinpoint the genetic elements that are present in placental mammals but missing from marsupials to learn more about what makes the two groups different.

The researchers were surprised to find that placental and marsupial mammals have largely the same set of genes for making proteins. Instead, much of the difference lies in the controls that turn genes on and off.

"Twenty percent of all the regulatory instructions in the human genome were invented after we part ways with the marsupials," Lander said.

"That was the first really important surprise about evolution—it's tinkering much more with the controls than it is with the genes themselves."

The scientists were also surprised to find that these regulatory sequences have in large part been distributed across the human genome by so-called jumping genes.

These genes have hopped through chromosomes for more than a billion years, leaving behind many copies of themselves. So until now the genes had been widely regarded by scientists as parasites, or "junk DNA," that played no creative role in evolution.

"It was a surprise that quite a significant proportion of all the new regulatory controls in the genome were coming from jumping genes," Lander said.

"It looks like [they are] a pretty major force for evolutionary innovation."

Advanced Immune System

The short-tailed opossum is native to South America and is also known as the Brazilian opossum and rain forest opossum.

The individual whose genome was sequenced came from a colony housed at the Southwest Foundation for Biomedical Research in San Antonio, Texas.

The animals have many features that make them ideal for scientific research, especially during early development, experts point out.

"Their biology is fascinating," said Jenny Grace, a biologist and marsupial expert at the Australian National University (ANU) in Canberra.

"Their young are born very tiny, the size of a penny."

The creatures are the only other mammals known to develop melanoma skin cancer solely from exposure to ultraviolet light, the cause of melanoma in most human cases.

Newborn opossums can also repair damage to their spinal cords, making them a focus of research into regenerative medicine.

"This shows us that it may not be that hard to grow spinal cords," said Lander, the Broad Institute director.

"Once you have a marsupial that can do something that a human or mouse can't do, you can compare the two," he added. "We're saying, wait, wait, it may not be that hard to grow spinal cords. Our closest cousins can do it. Let's see what tricks [they] have."

Scientists had also believed that marsupials have a primitive immune system.

"The genome project knocked that firmly on its head," ANU's Grace said.

"It turns out that marsupials have a very complicated immune system. It's just different from us."

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