Evolution caught playing with genetic on-off switch

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.