Wall Street Journal Apr 30, 2004

Wall Street Journal Apr 30, 2004. pg. B.1

Resurrecting Genes Helps Scientists Learn About Extinct Species

by Sharon Begley

ISSN/ISBN: 00999660

Full Text (845 words)

DNA HAS MANY fine qualities, what with that whole molecule-of- heredity thing it has going, but a long shelf life isn't among them. So even if you hit the scientific jackpot by finding cells preserved in amber (a la "Jurassic Park") or in ice (as with the Siberian mammoth that optimists tried to clone), chances are the DNA within will have seen better days. Deducing the identity of genes in these preserved cells is like reconstructing a wedding dress from a pile of dust.

To scientists forging the new field of "paleogenetics," such obstacles make their successes all the sweeter. Borrowing techniques used to figure out evolutionary trees that show who has descended from whom, and melding them with molecular biology, says biologist Joseph Thornton of the University of Oregon, Eugene, scientists can "raise a gene from the dead."

He means that almost literally. His is one of half a dozen new studies that have figured out the DNA sequence of an extinct gene, synthesized the gene and determined what it can do, offering insights into the lifestyles of the defunct and famous. "By resurrecting ancient genes, you can figure out a physiological or biochemical trait of an extinct species," Prof. Thornton says.

PALEOGENETICISTS typically start with the modern versions of a gene or protein. In a 2002 study, scientists led by Thomas Sakmar of Rockefeller University, New York, analyzed the modern gene for rhodopsin (a protein in the rods of the retina that lets you see in dim light) from alligators, pigeons, zebra finches and chicks. All of these are descendants of archosaurs, reptiles that lived 240 million years ago and are the direct ancestors of dinosaurs.

The scientists first constructed an evolutionary tree to deduce the most probable DNA sequence of the ancestral rhodopsin gene. (This step is akin to how linguists construct language trees: They compare the words for "mother" in several modern tongues, for instance, and then use what they know about how languages change to infer the word for "mother" in ancient Indo-European.) Next, the biologists used off-the- shelf chemicals to synthesize the ancient gene.

The rhodopsin it made, the Rockefeller team found, turns out to be quite adept at the biochemical steps that allow animals to see in the dark. That means the ancestral archosaur, and its dinosaur descendants, could see at night. Dinosaurs probably were active after sunset, something you would have no way of knowing without paleogenetics. Based on similar reasoning, Prof. Sakmar suspects the eye's cones, which see color in bright light, likely evolved before the rods, which see in the dark. Nocturnal creatures, it seems, are a fairly recent invention.

One of the first DNA resurrections throws light on ancient diets. Biochemist Steve Benner of the University of Florida, Gainesville, Fla., and colleagues sequenced genes from artiodactyls, hoofed animals including cows, camels and giraffes. The gene makes a digestive enzyme called ribonuclease. After inferring the ancestral form of the gene and synthesizing it in the lab, Prof. Benner's team put it through its paces.

The ancient gene, they found, makes an enzyme that is just as effective at chopping up food molecules as today's enzymes. That suggests ancestral cows and camels, 40 million years ago, ate hard-to- digest grasses, evolving that talent just when grasses first emerged.

PROF. BENNER holds the record for the most ancient resurrection. A gene called EF-Tu regulates how speedily organisms make proteins inside their cells. This is as basic a function as you can get, since proteins run biochemical reactions and are the materials of which cells are made. The ancestral gene, which existed as long as two billion years ago, worked best at 150 degrees Fahrenheit, the Florida scientists found. That suggests early forms of life appeared in a toasty environment such as hot springs or near undersea volcanoes.

In Prof. Thornton's lab, he and colleagues walked back the genes for hormone receptors. The ancestral receptor, which existed at least 600 million years ago, was almost indistinguishable from today's estrogen receptor, they found last year. That suggests estrogen, which is made from testosterone and other steroids, is the grandmother of all steroid hormones.

That may answer the chicken-and-egg question, "which came first, a hormone or its receptor?" At first, it seems, other hormones existed only to produce estrogen. But when lucky mutations in the estrogen receptor created receptors for testosterone and the others, these chemicals suddenly became full-fledged hormones.

Resurrecting genes still has a big dollop of art in its science. For one thing, inferring the sequence of ancient DNA from its descendants requires assumptions, which is why the technique is called "maximum likelihood" and not "we're sure about this."

Nevertheless, "the field has exploded in the last six months," Prof. Benner says. Although raising ancestral DNA from the dead is no easy feat, as the techniques become more practical and affordable, "more and more ancient genes are likely to be resurrected," Prof. Thornton writes in Nature Reviews Genetics. It is the next-best thing to raising T. rex. And a lot safer.

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