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May 9, 2007

Evolution caught playing with genetic on-off switch

Opossum genome shows 'junk' DNA source of genetic innovation
By Alvin Powell
Harvard News Office
A tiny opossum's genome has shed light on how evolution creates new creatures from old,
showing that change primarily comes by finding new ways of turning existing genes on and off.
The research, by an international consortium led by the Broad Institute of MIT and Harvard,
revises our understanding of genetic evolution. Scientists previously thought that evolution
slowly changed the genes that create specific proteins. As the proteins changed, so did the
creatures that owned them.
The current research shows that opossum and human protein-coding genes have changed little
since their ancestors parted ways, 180 million years ago. It has been the regulation of their
genes - when they turn on and off - that has changed dramatically.
"Evolution is tinkering much more with the controls than it is with the genes themselves," said
Broad Institute director Eric Lander. "Almost all of the new innovation ... is in the regulatory
controls. In fact,
marsupial mammals and placental mammals have largely the same set of protein-coding
genes. But by contrast, 20 percent of the regulatory instructions in the human genome were
invented after we parted ways with the marsupial."
The research, released Wednesday (May 9) also illustrated a mechanism for those regulatory
changes. It showed that an important source of genetic innovation comes from bits of DNA,
called transposons, that make up roughly half of our genome and that were previously thought
to be
genetic "junk."
The research shows that this so-called junk DNA is anything but, and that it instead can help
drive evolution by moving between chromosomes, turning genes on and off in new ways.
The research - the first time a marsupial genome was decoded involved the gray, short-tailed
opossum, a native of South American rain forests that is small enough to fit in the palm of
one's hand. Marsupials, which include kangaroos and koalas, have young that do much of their
development in a pouch outside the mother's body instead of in an interior womb as in
humans and other "placental mammals." The work was published in the May 10 issue of the
journal Nature.
The current research follows on the Broad's genome decoding effort in recent years that has
focused on placental mammals such as humans, chimpanzees, dogs, and mice. Lander said it
was this work that set the stage for the new understanding of the importance of regulation of
protein-coding genes in evolution.
It had been initially thought that most of a creature's DNA was made up of protein-coding
genes and that a relatively small part of the DNA was made up of regulatory portions that tell
the rest when to turn on and off.
As studies of mammalian genomes advanced, however, it became apparent that that view was
incorrect. The regulatory part of the genome was two to three times larger than the portion
that actually held the instructions for individual proteins.
"The official textbook picture of how genes work really didn't appear to be right," Lander said.
"There was much more of the genome standing around shouting instructions than actually
producing proteins."

That raised a question of how evolution actually works on the genome, Lander said. With so
much of the genome devoted to regulation, it became apparent that evolution could work by
simply changing the instructions rather than changing the protein-coding genes themselves.
The opossum genome provided an important point of comparison because it is more distantly
related to humans than other mammals whose genomes had been studied. While the common
ancestor of humans and opossums split 180 million years ago, the common ancestor of
humans and mice split just 80 million years ago.
The research will also prove useful for those seeking to understand opossum biology, according
to other researchers involved in the project. Opossums are important models for human
disease studies because they're the only animal other than humans who develop melanoma skin cancer - after exposure to ultraviolet radiation. They are also used in nervous system
research because baby opossums can regenerate their spinal cord tissue after it is cut and
regain the ability to move their limbs.
2007 The President and Fellows of Harvard College