August 14, 2003

Genome Study Finds Rats, Humans Share Stretches of DNA

Aug. 14--Dogs may be man's best friend but rats are closer relatives, according to a new study that compares stretches of DNA for 13 different animals -- including human beings.

We primates share common stretches of DNA with rats and mice that weren't found in carnivores such as dogs and cats or hoofed animals such as pigs and cows. The researchers, who published their paper in today's issue of the journal Nature, also studied DNA from two fellow primates -- baboons and monkeys -- as well as chickens, zebrafish and two species of pufferfish.

The researchers also looked at previously studied DNA from horses and found they were more closely related to dogs than they were to cows.

Eric Green, scientific director at the National Human Genome Research Institute, said he and his colleagues set out on this project not to rebuild the tree of life but to get better medical mileage out of the $3 billion Human Genome Project.

That massive undertaking read out the whole complement of DNA for a sample of human beings, leaving scientists with an enormous pile of data. Now they are struggling to use it to improve human health and longevity.

"We have the sequence of the human genome and how we need to figure out how it works," Green said. What we need now, he said, is a "parts list" -- an inventory of the useful parts of the genetic code.

The problem is that most of the three-billion-letter code carried by human DNA -- the human genome -- appears to be made of "junk," filler that doesn't perform any important function, he said. Only 1.5 percent of the whole genome is made up of actual genes -- stretches of DNA holding a recipe for making some kind of biological substance.

Green said they suspect that an additional 3.5 percent of human DNA serves some important purpose. To sleuth out the useful parts from all the junk, they reasoned that they should look for those stretches of code shared by many different creatures.

"This is now starting to show a way to highlight the regions of our genomes that are functionally significant," Green said.

The more critical the piece of DNA, the more likely it is to be shared by many species. The more junky the DNA, the more it can vary not only between species but between individuals within a species. This is the part of the DNA that police find useful for forensics because it varies so much from person to person.

Green said the region of DNA the team studied included the cystic fibrosis gene along with massive amounts of possible junk. He said some patients with cystic fibrosis don't appear to carry any mutations in that gene, possibly because their mutations occur in the surrounding DNA. Other genetic diseases may also involve mutations in stretches of DNA formerly written off as junk.

The new evidence for our close kinship with rodents came as a side benefit of the work. For decades, scientists assumed that rodents branched off from our ancestors very early -- far earlier than did other mammals, such as cats and pigs, said Blair Hedges, a Pennsylvania State University evolutionary biologist. But over the last several years, a number of genetic analyses have been pointing to a much more recent common ancestor.

"This is more convincing than anything I've seen before," he said. Still, he noted that mouse DNA differs significantly from human DNA because it has evolved faster, possibly because mice go through dozens of generations for every one of ours. That is, mice and rats have evolved further than we have from our common ancestor -- some kind of small furry mammal that lived 70 million to 100 million years ago.

It was during this era, the age of the dinosaurs, that mammals split into different branches, setting the template for our current tree of life, said paleontologist Ted Daeschler of the Academy of Natural Sciences.

At that time, the niches for big animals were all filled by dinosaurs. Mammals were all small, shrew-like creatures, but they had started to diverge into different branches, Daeschler said. When the dinosaurs went extinct 65 million years ago, "a lid was taken off," he said, and mammals started to grow into diverse forms, everything from whales to bats.

The team that did this recent study is now busy adding more animals -- wallabies, bats, elephants and other creatures. Penn State's Hedges said this should add much to our understanding of evolution.

"We need a few more years and a lot more species before we can really get a better picture of the tree of life."


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