Scientists Recreate Genome of Ancient Human Ancestor

John Roach
for National Geographic News
January 25, 2005
Scientists have recreated part of the genetic code of an extinct, shrewlike creature that is thought to have been the most recent common ancestor of most placental mammals, including humans.

Placental mammals give birth to live young, and they descended from a common ancestor scientists simply call the "boreoeutherian ancestor." The creature scurried about the woodlands of Asia more than 70 million years ago.

In recreating part of its genetic code, researchers say their goal wasn't to bring back the dead à la Jurassic Park (see sidebar). Rather, the scientists say their goal is to better understand human biology and evolution.

"The main reason we did this was to learn something about our [own] genome and the way genomes evolve within the mammal kingdom," said Mathieu Blanchette, an assistant professor in the school of computer science at McGill University in Montreal, Canada.

Genome Stories

David Haussler, an investigator with the Howard Hughes Medical Institute at the University of California, Santa Cruz, joined Blanchette in his quest.

As Haussler explains, genomes read like a story, the text of which is written in a genetic alphabet of a's, c's, g's, and t's—shorthand for nitrogen-containing compounds known as bases: adenine, cytosine, guanine, and thymine.

The text of a genome contains instructions on how to build arms, legs, hearts, lungs—an entire body—and is stored in every mammalian cell.

Haussler noted that there is a common theme to the genome texts of placental mammals, since they are all derived from a common, ancient ancestor.

"A change here and a change there in this genome text converted it into a recipe for a human being. A different set of changes converted it into a recipe for a whale. A yet different set of changes into a recipe for a dog, and so forth," Haussler said.

To find out what those text changes were, Blanchette, Haussler, and their colleagues used a computer program to compare and contrast the known DNA sequences of 19 of the ancestor's living relatives, including species of pig, horse, cat, dog, bat, mouse, rabbit, gorilla, chimpanzee, and human.

The results allowed the scientists to reconstruct a DNA sequence common to each species, including their common ancestor, thought to be the mother of most placental mammals.

This common ancestor has no scientific name, Haussler said. It is known simply as the "boreoeutherian ancestor" because boreoeutheria are the largest clade, or group of species, of mammals.

The scientists are uncertain precisely when the boreoeutherian ancestor lived. But they say it definitely was more than 70 million years ago.

Based on computer simulations and comparisons with living mammals, the researchers estimate their partial reconstruction of boreoeutherian ancestor's genome is 98 percent accurate.

The research was published in the December 2004 issue of the journal Genome Research.

The lead author of the study, Blanchette conducted his research while he was a postdoctoral student under Haussler at the University of California, Santa Cruz. Additional co-authors include Eric Green of the Human Genome Research Institute in Bethesda, Maryland, and Webb Miller of Pennsylvania State University.

Evolution Insight

Blanchette said knowing the genome of the ancestor to most placental mammals will allow scientists to see how individual genes have evolved and to better understand the role of genes in making an organism tick.

One example Blanchette points to is research led by Svante Paabo, a geneticist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. Paabo's investigation revealed that various mutations in a gene known as FOXP2 probably played a role in the evolution of speech in humans.

"By studying the history of this gene, [scientists] were able to understand the role of that gene," Blanchette said. "We hope to do that on a much larger scale, now on the whole genome."

For our boreoeutherian ancestor, Blanchette and colleagues have recreated a DNA sequence consisting of 1.1 million base pairs (the a's, c's, g's, and t's) around a region that flanks a gene linked to the disease cystic fibrosis.

The researchers chose the region because it had already been sequenced in a number of species as part of an effort led by study co-author Eric Green at the National Institutes of Health.

The complete genome of the boreoeutherian ancestor is estimated at three billion base pairs. That is roughly 3,000 times more base pairs than the segment Blanchette, Haussler, and their colleagues have recreated.

Blanchette said that once scientists sequence the complete genomes of several living placental mammals—a process that will take a few years and a lot of money—scientists could conceivably reconstruct most of the ancestral genome with 98 percent accuracy.

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